Clinical Research Protocols for Traditional Health Sciences (Ayurveda, Siddha, Unani, Sowa Rigpa and...

CENTRAL COUNCIL FOR RESEARCH IN AYURVEDA AND SIDDHADepartment of AYUSH, Ministry of Health & Family Welfare

Government of India, New Delhiwww.ccras.nic.in

CLINICAL RESEARCH PROTOCOLSFOR

TRADITIONAL HEALTH SCIENCES(AYURVEDA, SIDDHA, UNANI, SOWA RIGPA AND OTHERS)

INDEX

Sl. No. Subject Page

Forward III

Preface V

1. Section – I Respiratory System 1

1. 1.1 Allergic Bronchitis (Kasa) 5

2. 1.2 Bronchial Asthma (Tamaka shwasa) 33

2. Section – II Gastro intestinal System 61

1. 2.1 Irritable Bowel Syndrome (Kaphaja pravahika) 65

2. 2.2 Intestinal Helminthes Krimi roga (Gandupada krimi) 87

3. 2.3 Gall Stone Disease (Pittashmari) 111

4. 2.4 Sero conversion of HBsAg (carriers) (Yakrit vikara) 133

3. Section – III Joint Disorders 149

1. 3.1 Osteoarthritis-Knee Joint (Sandhi-vata) 153

2. 3.2 Rheumatoid Arthritis (Amavata) 185

3. 3.3 Osteoporosis (Asthisausirya) 231

4. Section – IV Ano-rectal Disorder 245

1. 4.1 Fissure-in-Ano (Parikartika) 249

2. 4.2 Piles (Arsha) 273

3. 4.3 Fistula-in-Ano (Bhagandara) 293

5. Section – V Nervous System 313

1. 5.1 Hemiplegia (Pakshaghata) 317

2. 5.2 Migraine (Ardhavabhedaka) 341

3. 5.3 Mental Retardation (Manasa Mandata) 357

4. 5.4 Sciatica (Gridhrasi) 387

5. 5.5 Anxiety Neurosis (Manodvega) 415

6. Section – VI Metabolic Disorders 437

1. 6.1 Obesity (Medoroga) 441

2. 6.2 Diabetes Mellitus (Madhumeha) 459

7. Section – VII Eye Disorders 479

1. 7.1 Cataract (Linganasha) 483

2. 7.2 Dry Eye Syndrome (Shushkakshipaka / Parishuskha 501Netra)

3. 7.3 Allergic Conjunctivitis (Kaphaja abhishyanda) 519

8. Section – VIII Connective Tissue Disorders 535

1. 8.1 Deep Vein Thrombosis 539

9. Section – IX Geriatric Disorders 557

1. 9.1 Rejuvenation (Rasayana) in healthy elderly persons 561

2. 9.2 Rejuvenation (Kaya kalpa) in healthy elderly persons 593

10. Section – X Reproductive System 615

1. 10.1 Menopausal Syndrome 619

2. 10.2 Dysfunctional Uterine Bleeding 643

3. 10.3 Dysmenorrhoea (Kashtartava) 661

11. Section – XI Cardio Vascular System 701

1. 11.1 Essential Hypertension (Uchcharaktachapa) 705

2. 11.2 Chronic Stable Angina (Hridroga) 727

12. Section – XII Urinary System 745

1. 12.1 Urolithiasis (Mutrashmari) 749

13. Section – XIII Vector Borne Diseases 769

1. 13.1 Kala-Azar 773

2. 13.2 Filariasis (Shleepada) 801

14. Section – XIV Haematological Disorders 827

1. 14.1 Iron Deficiency Anaemia (Pandu) 831

2. 14.2 Sickle Cell Anemia 865

15. Section – XV Immune System 883

1. 15.1 HIV Infected Persons 887

16. Section – XVI Disorders of Skin 911

1. 16.1 Psoriasis (Kitibha) 915

17. Section – XVII Reproductive and Child Health Care 941

1. 17.1 AYUSH AG TAB during Pregnancy 943

2. 17.2 AYUSH PG TAB in edema during pregnancy 958

3. 17.3 AYUSH B.R. Leham for immunity in infants 973

4. 17.4 AYUSH PK-Avaleha in preventing postpartum 985complications and puerperial care.

5. 17.5 AYUSH SS-Granules to ensure quality & quantity of 996breast milk

18. Section – XVIII Clinical Safety of some 1007Ayurveda and Siddha Drugs

1. 18.1 Clinical safety of herbo-mineral and metallic preparation 1011(Rasamanikya Rasa)

2. 18.2 Clinical safety of herbo-mineral and metallic preparation 1049(Vasantakusumakara Rasa).

19. Section – XIX Annexure 1071

1. 19.1 Case Report Form for determination of 1073Prakriti/Udaliyal/Mizaj

2. 19.2 Guidelines for Designing A Clinical Study Protocol 1083

3. 19.3 Patient Information Sheet 1089

Publisher

Central Council for Research in Ayurveda and SiddhaDepartment of AYUSHMinistry of Health and Family Welfare, Government of IndiaJ.L.N.B.C.E.H.Anusandhan Bhavan, 61-65, Institutional AreaOpposite D-Block, Janakpuri, New Delhi – 110058E-mail: [email protected], Website: www.ccras.nic.in

© Central Council for Research in Ayurveda and Siddha, New Delhi2010

Note: Reproduction/Translation/Citation of any part of this publication are welcome withdue acknowledgement of the Council for academic and research purpose. No citation forcommercial purpose is permitted.

Cover Page Designed by : Dr. N. Srikanth, Assistant Director (Ay.)

Printed at : Pearl Offset Press Pvt. Ltd., 5/33, Kirti Nagar Industrial Area, New Delhi - 110 015Tel. 011-25159312, 41424700, 41424800

III

FOREWORD

Ayurveda and Siddha have been in vogue in this country from the earliest times, servingthe medical needs of most of our people. These systems were developed by ancient scholars onthe basis of their own philosophy, oriental methodologies and practices prevalent in that era andhave popularized and almost completed it in all aspects as a system of medicine. The advent offoreign invasion and cross interaction had definite impact on these systems.

The worldwide interest in the use of natural products and plant-based remedies had led todifferent situations developing in different countries. In countries with a strong foundation oftraditional medicine such as India and China, nationally recognized parallel traditional systems haverun for long periods, along with Western medicine with varying degrees of acceptance, integrationand assimilation.

During the last decade, use of traditional medicine has expanded globally and has gainedpopularity. It has not only continued to be used for primary health care of the poor in developingcountries, but has also been used in countries where conventional medicine is predominant in thenational health care systems. With the tremendous expansions in the use of Ayurveda and Siddhaworld wide, the safety and efficacy as well as quality control of herbal medicines and traditionalprocedure-based therapies have become important concerns for both health authorities and thepublic. Various practices of traditional medicine have been developed in different cultures indifferent regions without a parallel development of international standards and appropriate methodsfor evaluating Ayurveda and Siddha systems of Medicine. Like other systems of ancient Indialearning Ayurveda was discovered through most suitable sources (Pramanas) viz. (1) Pratyaksha(direct perception), (2) Anumana (logical inference), (3) Aptopadesa (verbal and authenticdocumentary testimony) and (4) Yukti (experimental evidence) etc.

In modern medicine, a clinical trial is almost always undertaken to test the efficacy ofpharmaceutical products (drugs, devices etc.) and some times to study the efficacy of ‘non-therapeutic interventions’. The global acceptance of modern system of medicine as a whole isbecause it has been reviewed systematically by modern scientific parameters. Similar scientificevidences through clinical trials are the need of time, to make the traditional medical systemsscientifically acceptable by all.

While designing the research trials it would be appropriate to understand differencesbetween Ayurveda/ Siddha and Contemporary Modern System of Medicine. The differences aremainly due to the basic approach to Health and Diseases; perception and also epistemological.The Ayurveda is holistic in approach, in diagnosis, prognosis as well as management of diseases.Holistic approach of Ayurveda is indeed good and welcome in clinical practice (for the ‘patient’and the ‘society’). However, this approach has considerable difficulties and even challenges the

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scientists to devise parameters and design suitable models for clinical studies/trials. The pursuit ofa better understanding of the facts and phenomena in Ayurveda and Siddha, through scientificresearch will be able to fill this gap.

Only using the modern scientific tools without considering the holistic concepts of traditionalmedical system, may sometimes lead to inappropriate conclusions. This is high time to create thescientific evidences on Ayurvedic principles and practices taking into the consideration of basicprinciples and philosophies embodies in the literature and correlating them with the modernscientific concepts, which will rightly convey and translate the merits of Ayurveda and othertraditional systems of medicine.

The Central Council for Research in Ayurveda and Siddha has been engaged in scientificresearch in Ayurveda and Siddha since more than past three decades and executing researchadopting the integrative protocols. I appreciate the involvement of scholars from various reputedorganizations like Indian Council of Medical Research, All India Institute of Medical Sciences, LadyHarding Medical College, NIMHANS, Bangalore and other institutes while drafting and finalizingthe protocols.

The views and endorsement of experts from both Ayurveda and Allopathic systemsenriched the protocols providing a good scope of integrative research for creating scientificevidence.

As research methodology is a continuously evolving subject, one should always consult thecurrent updates and modify the protocols and formats as per the needs from time to time. Thisdocument would greatly serve as basic reference material for scientists and scholars who areinvolved in clinical research in Ayurveda, Siddha and other traditional systems of medicine.

I appreciate the efforts of CCRAS in bringing out this document and would certainlyreceive a warm welcome from scientists and scholars engaged in traditional medicine research.

(Dr. C.D. Tripathi)Professor and Head

Department of Pharmacology

Vardhman Mahavir Medical College

& Safdarjung Hospital

New Delhi

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PREFACE

Research is essential for development of any science. This is even more necessary inrespect of ancient sciences like Ayurveda and Siddha. The various schemes and initiatives ofGovernment of India led to establishment of a National body “Central Council for Research inIndian Medicine and Homeopathy (CCRIMH) in 1969. The Central Council for Research inAyurveda & Siddha was started in 1978 as a successor to CCRIMH, for research in Ayurvedaand Siddha.

The Central Council for Research in Ayurveda & Siddha, Department of AYUSH, Ministryof Health & Family Welfare, Government of India is an apex Nodal Body in India for theformulation of Research in Ayurveda and Siddha on scientific lines. The research activities ofCCRAS include Literary Research, Drug Research, Clinical Research including NutraceuticalsResearch, Cosmeceutical Research and Bio-medical instrumentation and Reproductive and ChildHealth Care Research. The Council has been carrying out its research activities through thenetwork of the peripheral institutes across the country and also in collaboration with variousNational and International academics and Research Organizations.

The Council is executing research studies on scientific lines as per the prevalent guidelineswith Ayurveda and Siddha related part so as to make it integrative in nature. The Council hascurrently undertaken execution of clinical trials on more than 30 priority areas on phased manneradopting the current norms of drug development process viz. pre-clinical standardization/toxicitystudies and phased clinical trials.

The integrative research protocols and Case Report Forms (CRFs) incorporating basicprinciples of Ayurveda and current requirement and methodology of research etc. have beendeveloped from time to time through extensive consultative process involving high profile expertsin the field of Ayurveda and Allopathic system of medicine from reputed institutes viz. AIIMS,ICMR, CSIR, NIMHANS and so on.

Dissemination of these methodologies by publishing the formats of selected diseases alongwith protocols, Case Report Forms (CRFs) would help the scientists, academicians, PG and

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Ph.D. scholars etc. who wish to conduct research on different diseases/conditions in developingprotocols and serving as a basic reference material. However, the specific protocol could bedeveloped by individuals suitable to their needs based on the specific objectives.

There has been a great need for a comprehensive compendium of Protocol formats andCase Report Forms (CRFs) for ready reference of research scholars, scientists etc. Keeping thisin view the Council is publishing the present compendium and I am convinced that this will be ofimmense help not only for researchers more so ever to the Post Graduate and DoctorialScholars.

I am highly thankful to Dr. C. D. Tripathi, Professor & Head, Deptt. of Pharmacology,Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi for sparing his valuabletime by offering suitable suggestions that has made this document more authentic and scientific.

I greatly appreciate the scientists of CCRAS, expert members of task force whose effortsmade this work possible. I also appreciate Dr. M.M. Sharma, Dr. B.S. Sharma, Mr. UpendraSingh & Mr. Narender Singh from publication section for their tireless efforts in bringing out thispublication, Mr. Gaurav Kumar and Mr. Prasanto Choudhary, Data Entry Operators for secretarialassistance.

New Delhi (Prof. G.S. Lavekar)Director General

CCRAS

VII

CHIEF EDITOR

Prof. G.S. LAVEKARDirector General

Central Council for Research in Ayurveda and Siddha, New Delhi

EXPERT REVIEWER

Dr. C.D. TRIPATHIProfessor & Head

Department of PharmacologyVardhman Mahavir Medical College & Safdarjung Hospital, New Delhi

EDITOR

Dr. M.M. PADHIDeputy Director (Technical)


PROGRAMME COORDINATOR

Dr. N. SRIKANTHAssistant Director (Ay.)


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Dr. M.M. RaoDeputy Director (Ay.)

CCRAS, New Delhi

Dr. Sobran SinghAssistant Director (Ay.)

CCRAS, New Delhi

Dr. Adarsh KumarAssistant Director (Ay.)

CCRAS, New Delhi

Dr. G.C. BhuyanResearch Officer (Ay.)

CCRAS, New Delhi

Dr. Sarada OtaResearch Officer (Ay.)

CCRAS, New Delhi

Dr. Banamali DasResearch Officer (Ay.)

CCRAS, New Delhi

Dr. M.M. SharmaResearch Officer (Ay.),

CCRAS, New Delhi

Dr. B.S. SharmaResearch Officer (Ay.),

CCRAS, New Delhi

Dr. S.K. MeherResearch Officer (Ay.),

CCRAS, New Delhi

Dr. A.C. KarEx. Asst. Director (Ay.)

CCRAS, New Delhi

CORE SCIENTIFIC GROUP

Dr. Sulochana BhatAssistant Director (Ay.)

CCRAS, New Delhi

Dr. T. AnandanAssistant Director (Siddha)

Central Research Institute (Siddha) Chennai

Dr. G. Ganapathi RamanEx. Asst. Director (Siddha)

CCRAS, New Delhi

R.K. SinghalStatistical Officer

CCRAS, New Delhi

Dr. M.K. JhaEx. Research Officer (Medicine)

CCRAS, New Delhi

Dr. B. VenkateshwarluResearch Officer (Ay.)

CCRAS, New Delhi

Dr. K. Prameela DeviResearch Officer (Ay.)

CCRAS, New Delhi

Dr. S.K. VediResearch Officer (Ay.)

CCRAS, New Delhi

Dr. K. BharatiAssistant Director (Ay.)

IIHM, Hyderabad

Dr. GalibEx. Research Officer (Ay.),

CCRAS, New Delhi

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TASK FORCE OF EXPERTS FROM REPUTEDINSTITUTES

All India Institute of Medical Sciences, New Delhi

Dr. M.V. PadmaAdditional Professor

Department of NeurologyAIIMS Ansari NagarNew delhi-110029

Prof. Y.K. GuptaHead of Department

Department of PharmacologyAIIMS Ansari NagarNew Delhi - 110029

Dr. Nikhil TandonAddl. Professor EndocrinologyAIIMS New Delhi – 110029

Prof. K.K. TalwarProf.& HOD, Cardiology

AIIMS Ansari NagarNew Delhi – 110029

Dr. Suneeta MittalProfessor & HOD

Department of Obstetrics and GynaecologyAIIMS Ansari NagarNew Delhi – 111029

Prof. S.K. SharmaHead of Department

Department of MedicineAIIMS Ansari NagarNew Delhi – 110029

Dr. S.C. MahaptraProfessor

Department of PhysiologyAIIMS Ansari NagarNew Delhi – 110029

Dr. Jasbir KaurAsst. Professor

Dr. R.P. Centre for Ophthalmic SciencesAIIMS New Delhi – 110029

Dr. Monoranjan MahapatraAssoc. Professor EndocrinologyAIIMS New Delhi – 110029

Prof. Anita PandaDr. R.P. Centre for Ophthalmic Sciences

AIIMS Ansari NagarNew Delhi – 110029

Dr. Neena ValechaDeputy Director

Malaria Research Centre (ICMR)New Delhi

Dr. Nandani KumarEx. Deputy Director General

ICMRAnsari Nagar

New Delhi – 110029

Indian Council for Medical Research, New Delhi

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Dr. Abha Rani AggarwalScientist E

National Institute of Medical StatisticsICMR Head Quarters Campus

Ansari NagarNew Delhi – 110029

Dr. Arvind PandeyNational Institute of Medical Statistics

ICMR Head Quarters Campus, Ansari Nagar

New Delhi – 110029

Banaras Hindu University, Varanasi

Prof. Dr. Manjari DwivediDepartment of Prasuti Tantra & Stree Roga

Institute of Medical Science (Ayurveda),Banaras Hindu University

Varanasi – 221005

Prof. I.S. GambhirDepartment of Medicine

Institute of Medical SciencesBanaras Hindu University

Varanasi – 221005

Prof. R.G. Singh,Department of NephrologyBanaras Hindu University

Varanasi – 221005

Prof. Dr. P.V. TiwariDepartment of Prasuti Tantra & Stree Roga

Institute of Medical Science (Ayurveda)Banaras Hindu University

Varanasi – 221005

Vallabh Bhai Patel Chest Institute,University of Delhi, Delhi

Dr. S.C. ManchandaDepartment of CardiologySir Ganga Ram Hospital

Rajinder Nagar, Delhi – 110060

Prof. Ashok ShahDepartment of Respiratory Medicine,

Vallabh Bhai Patel Chest InstituteUniversity of Delhi, Delhi

Sir Ganga Ram Hospital, Delhi

Ayurvedic & Siddha Experts

Dr. B.V. Sathe30/2, 4 Erandvan

Flat No. C-1, Vihar SocietyNear Mahendle Garage

Pune - 411004

Dr. S.K. MishraEx. Advisor (Ay.)

Department of ISM&HMinistry of Health & Family Welfare

Govt. of India

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Dr. S.M. SathePlot No. 9

Gananjay Society Unit – 1Azad Nagar, Kothrud

Pune – 411038

Dr. G. VeluchamyEx. Director CCRAS,

New Delhi

Dr. K.D. SharmaEx. Deputy Director (Technical)

CCRAS, New Delhi

TECHNICAL SUPPORT

Dr. Seema Jain,Senior Research Fellow (Ay.),

CCRAS, New Delhi

Dr. Senthilvel,Research Officer (Siddha),

CCRAS, New Delhi

R.K. Rana,Statistical Assistant,

CCRAS, New Delhi

Richa Singhal,Senior Research Fellow (Statistics),

CCRAS, New Delhi

Dr. Syed Hissar,Research Officer (Medicine),

CCRAS, New Delhi

Dr. Selvarajan,Research Officer (Siddha),

CCRAS, New Delhi

Dr. Babita Yadav,Senior Research Fellow (Ay.),

CCRAS, New Delhi

Dr. Suprabhat Bhardwaj,Senior Research Fellow (Ay.),

CCRAS, New Delhi

Dr. Nikhil JirankalgikarSenior Research Fellow (Ay.),

CCRAS, New Delhi

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RESPIRATORY SYSTEM

SEC

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N - I

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Drug: Study Code:

CENTRAL COUNCIL FOR RESEARCH IN AYURVEDAAND SIDDHA

MULTICENTRIC CLINICAL TRIAL OF AYURVEDICFORMULATION IN THE TREATMENT OF KASA

(BRONCHITIS)

PROTOCOL & CASE REPORT FORMS (CRF)

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I. BACKGROUND

Kasa (Bronchitis)1is prevalent all over the world and certainly most common acute diseaseof lungs. It is characterized by inflammation of brochial tubes and is much more common inchildhood and after middle age. Attacks are much more likely to occur in the winter and springseasons. The disease commonly commences with symptoms of an acute respiratory infection anda slight sore throat. In the course of a day or so it affects the trachea and larger bronchi withfeeling of soreness behind the sternum, tightness in the chest, frequent and mainly dry cough anda rise in temperature. The voice becomes husky. The sputum is initially thick and scanty but lateron becomes more copious, mucopurulent and more easily to cough ups. In the cases of greatseverity, there is a severe bronchitis affecting the larger and smaller tubes, a high rising temperature(104o – 105o F), severe dyspnoea, cyanosis, and prostration. The sputum may be streaked withblood. Especially at extremes of life death may occur, or recovery will be taking 4-8 weeks.According to modern medicine, bronchitis may follow exposure to cold. In majority of cases thereis an infection of upper respiratory tract. A number of drugs including antibiotics are available forthe successful treatment of the disease but recurrence of the condition, development of bacterialresistance against drug is now a days common. Besides of these number of side effects, adverseeffects of antibiotic therapies have been reported time to time. So it is better to seek for a safeand effective alternative treatment for the cure.

The disease is very well described in Ayurveda and a number of drugs have beenmentioned. Vyaghriharitaki is one of the classical compound drugs which has been in practice sinceancient times for its successful treatment. A protocol is designed here with special reterenceVyaghriharitaki which may be principally utilized for management with suitable ammendments.

CENTRAL COUNCIL FOR RESEARCH IN AYURVEDA AND SIDDHA

MULTICENTRIC CLINICAL TRIAL OF AYURVEDIC FORMULATION IN THETREATMENT OF KASA (BRONCHITIS)

References

1. Charaka Samhita; Chaukhamba Publication, Varanasi; 2nd Edition; Sutra Sthana, Chapter 25, Verses 40

2. Savill’s System of Clinical Medicine- revised and edited by E.C.Warner, 14th edition, page No. 183- 186

3. Davidson’s Principle and Practice of Medicine 18th Edition pages 339

4. Charaka Samhita; Chaukhamba Publication, Varanasi; 2nd Edition; Chikista Sthana, Chapter 18, Verses 10&133

5. www.emedicinehealth.com

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II. OBJECTIVES

1. To evaluate the clinical efficacy of Vyaghriharitaki in the cases of Kasa (bronchitis)

2. To validate the clinical efficacy of Ayurvedic drug Vyaghriharitaki on the scientificparameters in the patients of Kasa (bronchitis)

3. To evaluate the safety of Vyaghriharitaki in the patients of Kasa (bronchitis).

III. CENTRES

CCRAS centers in collaboration with other centers

IV. SAMPLE SIZE & METHODS

Sample size — 120 (60 patients in each group)

Design of the study — Open clinical study.

Drug/Dosage/Duration

Group – A — Vyaghriharitaki without restriction of pathyapathya(Restrictions related to diets and life style).

Group – B — Vyaghriharitaki with restrictions of pathyapathya

Dose & Duration — 2.5 gm B.D. for 1 (one) month

Total period — 1 year and 6 months to complete the study

V. CRITERIA FOR INCLUSION

1. Patients of either sex with Age between 15 years to 60 years

2. Cases with confirmed diagnosis by signs/symptoms/lab findings of bronchitis.

3. Duration of illness not more than 6 months.

4. Repeated attacks of bronchitis

5. Smokers.

VI. CRITERIA FOR EXCLUSION

1. Age below 15 years and more than 60 years

2. Cough associated with other respiratory disorders like Bronchial carcinoma, BronchialAsthma, Bronchiectasis, cases of tuberculosis, interstitial lung disease/occupational Lungdisease, tropical pulmonary eosinophilia, Loffler`s disease, Allergic BronchopulmonaryAspergillosis etc.

3. Diabetes Mellitus, Hypertension and other serious cardiovascular disorders.

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4. Severe renal/Hepatic disease

5. HIV positive cases

6. Pregnant/lactating mother

7. Any other serious systemic disease.

VII. CRITERIA FOR WITHDRAWAL

During the course of the trial treatment, if any serious condition or any serious adverseeffect / event which requires urgent treatment or if patient by own wants to withdraw from thestudy, such subjects may be withdrawn from the trial and managed by the Principal Investigatoraccordingly.

VIII. ROUTINE EXAMINATION AND ASSESSMENT

Screen of the patient will be recorded as per the proforma (Form I). The full details ofhistory and physical examination of the patients will be recorded as per the proforma (Forms II).Clinical assessment will be done before treatment, at 15 days of treatment period and at the end ofthe treatment as per proforma - III. The laboratory investigations will be carried out before and aftertreatment as recorded as proforma - IIIA. Adverse events will berecorded in the proforma - IV.

IX. STATISTICAL ANALYSIS

Data collected will be analyzed using appropriate statistical tools.

X. CRITERIA FOR ASSESSMENT

The assessment of progress & outcome of treatment are assessed on the basis ofimprovement in the score of clinical signs and symptoms and laboratory findings and safetyevaluation will be made on the basis of serial recording of the adverse events if any and Liver andKidney function tests as PROFORMA II B and III.

XI. TRIAL MONITORING AND STATISTICAL ANALYSIS

Data on clinical symptoms and objective tests before and after the treatment will betabulated and analyzed using appropriate statistical tools. However the data of each case will haveto be communicated on completion of trial therapy to the Statistical Officer of CCRAS through e-mail ([email protected]). The monitoring of progress of the trial will also be undertaken byCCRAS Hqrs. New Delhi.

XII. ETHICAL REVIEW

A. Institutional Ethical Committee (IEC): The proposal will be placed before InstitutionalEthical Committee (IEC) of trial centre for getting clearance certificate before the projectis initiated. Patient’s information sheet and informed consent form will be submitted alongwith project proposal for approval by IEC.

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B. Data and safety monitoring board: A Data and safety monitoring board (DSMB) atHqrs will carefully monitor the data and side effects during the period of study and put ina place where by prompt reporting of adverse events occur and take appropriate steps incase of any adverse events occur. The data will be reviewed for every 20 participantsincluded into the study and administered the trial drugs. The research team will reportimmediately to the PI and Data Monitoring Board, any life threatening conditions whetherthey are perceived to be study related or not. The Board will decide whether the adverseeffects warrant discontinuation of the study protocol or not. Protocols will be written andapproved for the treatment of study related adverse events about the clinical trial conductand laboratory procedures in order to maintain the uniformity.

XIII. TRAVELING EXPENSES FOR RESEARCH SUBJECTS

A consolidated amount of Rs…../- per visit will be paid to each subject as an incentive.

XIV. TRAINING TO INVESTIGATORS AND PERSONS INVOLVED

Short-term two-day training will be provided to the Investigators and Laboratorypersonnel involved in the multi-centric trial at C.C.R.A.S. Hqrs. and Central Research Institute(Ay.), New Delhi. The investigators and technicians will be detailed about the clinical trial conductand laboratory procedures in order to maintain the uniformity.

XV. LABORATORY INVESTIGATIONS

The Laboratory Investigations (Pathological/Biochemical, etc.), which are not available atresearch Institutes should be conducted at identified reputed labs /Government Institutes underintimation to this Council following codal formalities.

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ASSESSMENT OF THERAPEUTIC EFFICACY & SAFETY OFVYAGHRIHARITAKI IN THE MANAGEMENT OF KASA (BRONCHITIS)

WRITTEN INFORMED CONSENT FORM

CERTIFICATE BY INVESTIGATOR

I certify that I have disclosed all details about the study in the terms easily understood bythe patient.

Date: _______________ Signature of the subject: ______________

Name: ____________________________

CONSENT BY SUBJECT

I have been informed to my satisfaction, by the attending physician, the purpose of theclinical trial and the nature of drug treatment and follow-up, including the laboratory investigationsto be performed to monitor and safeguard my body functions.

I am also aware of my right to opt out of the trial at any time during the course of the trialwithout having to give the reasons for doing so.

I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “Assessment of Therapeutic Efficacy & Safety of Vyaghriharitaki in themanagement of Kasa (Bronchitis)

Date:___________ Name of the Subject:_____________________________

Signature or Thumb impression_____________________

Date:___________ Name of witness: _______________________________

Signature or Thumb impression: _____________________

Relationship ___________________________________

To be translated into regional language.

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PATIENT INFORMATION SHEET

What is the study about?

Kasa (Bronchitis) is prevalent all over the world and certainly most common acute diseaseof lungs. It is characterized by inflammation of bronchial tubes and is much more common inchildhood and after middle age. Attacks are much more likely to occur in the winter and springseason of the year. The disease commonly commences with symptoms of an acute respiratoryinfection and a slight sore throat. In the course of a day or so it affects the trachea and largerbronchi with feeling of soreness behind the sternum, tightness in the chest, a frequent and mainlyin dry cough and a rise in temperature. The voice becomes husky. The sputum is initially thick andscanty but later on becomes more copious, mucopurulent and more easily to cough ups.

The available treatment for bronchitis in modern medical science like antibiotics, antitussives, expectorants, bronchodilators etc. made tremendous success in providing instant orsymptomatic relief but there are certain side effects of these drugs. In Ayurveda, many drugs seemto possess better curative effect in the cases of Kasa (bronchitis) that have been in practice sinceyears successfully.

What will you have to do?

Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 1 month to complete. During thisperiod, you are expected to visit the hospital 3 times for clinical and/or pathological assessment.

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination, X-ray, blood and urine samples will also be taken. If you are found eligible,you would be put on trial treatment for 30 days.

At each visit, you will be supplied with sufficient quantities of drugs to last until your nextvisit. If any adverse reactions like skin allergy, nausea, vomiting and palpitation/tremor etc. arenoticed during the treatment period, this should be brought to the notice of the PrincipalInvestigator.


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CASE REPORT FORM I – SCREENING

BEFORE TREATMENT

(Enter a � in the appropriate box)

1. Centre: ………………..……….

2. Code No. (of clinical trial)

3. Name of the subject: ………………………………........…………………………………

4. Gender: Male (1) Female (2)

5. Date of Birth: Age (in yrs.) :

6. Address ……………………………………..………………………………………

CRITERIA FOR INCLUSION Yes (1) No (0)

1. Age between 15 to 60 years

2. Both the sexes irrespective of caste/religion.

3. Uncomplicated cases of bronchitis.

4. Repeated attacks of bronchitis.

CRITERIA FOR EXCLUSION Yes (1) No (0)

5. Age below 15 years and above 60 years.

6. Cough associated with other respiratory disorderslike Bronchial carcinoma.

7. Bronchial Asthma, Bronchiectasis, cases of tuberculosis,

8. Interstitial lung disease/occupational Lung disease, tropical

9. Pulmonary eosinophilia, Loffler s disease, AllergicBronchopulmonary Aspergillosis etc

12

10. Diabetes Mellitus and Hypertension and otherserious cardiovascular disorders.



A patient is eligible for admission to the trial

If Sl.No.1-4 is ‘Yes’ and Sl.No.5-12 are ‘No’

If admitted, Sr. No. of the Subject: _________________________

No. of packets issued: _________________________

Date: __________________ Signature of the investigator: ___________________

13



CASE REPORT FORM II – HISTORY


1. Centre: ………………..……….


3. Sr. No. of the subject: ……………………………........…………………………………

4. Name of the Subject: ...........................................................................................................



7. Address ……………………………………..……………..........…………………………

8. Educational status: Illiterate (1) Read and Write(2) Primary School (3)

Middle School (4) High School (5) College (6)

Other (specify) (7) I.N.A. (8)

9. Occupation: Desk work(1) Field work (2)

Field work with physical labour (3)

Field work with intellectual (4)

Indicate nature of work: ...........................................................................

10. Income (per capita per month in Rs.): ____________________________of the participant and Head of the family

Chief complaints with duration (in days) Yes (1) No (0) Duration(in days)

11. Cough (Dry/Productive)

14

12. Sputum - Thick and scanty/Mucoid/Mucopurulent/Streaks with blood

13. Dyspnoea

14. Wheezing

15. Chest Pain

16. Tightness in chest

17. Fever

18. Sore throat

19. Onset of disease Acute (1) Chronic (2)

20. Previous episodes Yes (1) No (0)

21. Treatment given so far: Traditional Medicine (1) Modern Medicine (2)

PERSONAL HISTORY

22. Diet Veg (1) Non-veg (2)

23. Sleep Normal (1) Duration in hours______________________

Abnormal(2) Duration in hours______________________

24. Constipation Yes (1) No (0)

25. Addiction Yes (1) No (0)

a). Smoking

If yes specify: (a) Quantity [packs]:__________________

(b) Total Duration in years: ____________

b). Tobacco Yes (1) No (0)



15

c). Alcohol Yes (1) No (0)

If yes specify: (a) Quantity (ml)_________

(b) Total Duration in years_______________

d). Any other (specify)________________

26. Sharirika Prakriti: Vata (1) Pitta (2) Kapha (3)

Vata-Kaphaj(4) Vata-Pittaja (5) Pittaja-Kaphaja(6)

Sannipataj (7)

27. Manasa Prakriti: Satwika (1) Rajasa (2) Tamasa (3)

PHYSICAL EXAMINATION

28. Built Lean (1) Medium (2) Heavy (3)

29. Gait Normal (1) Abnormal (0)

30. Body weight _________Kg.

31. Height in cms._________

32. Body temperature ____________o F

33. Blood pressure (in sitting posture of right upper limb):

Systolic _______mm/Hg Diastolic _______mm/Hg

34. Pulse rate__________/min. (Radial pulse of right upper limb)

35. Respiration rate _________/min.

Present (1) Absent (0)

36. Pallor

37. Jaundice

38. Koilonychia

39. Cyanosis

40. Lymphadenopathy

16

SYSTEMIC EXAMINATION

41. Digestive system Normal(1) Abnormal(0)

If Abnormal, specify abnormalities_________________________

42. Abdomen Palpable (1) Not palpable (2)

i) Liver

ii) Spleen

Normal (1) Abnormal (2)

43. CNS

If abnormal, specify abnormalities_____________________________

44. CVS with chest


45. Uro-genital system


46. Respiratory system


SAMPRAPTI (PATHOGENESIS)

Vata (1) Pitta (2) Kapha (3)

47. Anubandhya dosha

48. Anubandh dosha

49. Avaraka dosha

50. Ksheen dosha

51. Ksheen dhatu Rasa (1) Rakta (2) Mamsa(3)

Meda(4) Asthi (5) Majja (6)

Shukra(7) Ojas (8)

17

52. Dushya (Involved) Rasa (1) Rakta(2) Mamsa (3)

Meda (4) Asthi (5) Majja (6)

Shukra (7) Ojas (8)

53. Stages of disease (Roga Kriya Kala)

Sanchaya(1) Prakopa(2) Prasara (3)

Sthan Sanshray (4) Vyakti (5) Bheda (6)

Srotas Pareeksha

54. Pran vaha srota

Alpa Alpa Swasa (Shortened Breathing) (1)

Atisrama Swasa (Increased respiration rate) (2)

Abhikshana Swasa (Chyne stroke breathing) (3)

Kupit Swasa (Vitiated breathing) (4)

Sashula swasa (Dyspnoea with pain) (5)

55. Udakavaha srota

Jihva sosha (Dryness of tongue) (1)

Oustha sosha (Dryness of lip) (2)

Talu sosha (Dryness of palate) (3)

Kantha sosha (Dryness of throat) (4)

Kloma sosha (Excessive thirst) (5)

Trishna (Thirst) (6)

56. Annavaha srota

Anannabhilasha (Lack of desire for food) (1)

Aruchi (Anorexia) (2)

18

Avipaka (Indigestion) (3)

Chhardi (Vomitting) (4)

57. Rasa Vaha srotas

Mukha vairsya (Bad taste in mouth) (1)

Arasajnata (Tastelessness) (2)

Hrillasa (Water brash) (3)

Gaurava (Feeling of heaviness) (4)

Tandra (Stupor) (5)

Anga marda (Body ache) (6)

Jwara (Fever) (7)

Pandu (Anaemia) (8)

Avsada (Depression) (9)

Klibya (Loss of libibo) (10)

Karshya (Emaciation) (11)

Agnimandya (Diminished appetite) (12)

58. Rakta vaha srotas

Pidika (Boils) (1)

Rakta Pitta (Bleeding from any of the orifice) (2)

Mukha Pak (Stomatitis) (3)

Vidradhi (Abscess) (4)

Charma roga (Skin disease) (5)

Kamala (Jaundice) (6)

19

59. Mamsavaha srotas

Arubud (Tumour) (1)

Aljee (Phlyctenular conjunctivitis) (2)

Gandamalaa (cervical lymphadenitis) (3)

Upji (Epiglotis) (4)

Adhimamsa (Protruberance of flesh/cancer/cyst) (5)

Putimamsa (decayed flesh/gangrene) (6)

60. Medo vaha srotas

Maladhikya (Excess of excreta) (1)

Hastapada daha (Burning sensation in the palm and sole) (2)

Hastapada suptata (Numbness of the palm and sole) (3)

Tandra (Stupor) (4)

Dehachikkanta (Greasiness of the skin) (5)

Alasya (Lethargy) (6)

61. Asthivaha srotas

Adhyasthi (Hypertrophy of bone) (1)

Adhidanta (Redundant tooth) (2)

Dantshoola (Toothache) (3)

Asthi shoola (Bone pain) (4)

Kesha, loma, nakha, samshru vikara (5)(Any defects of hair, hair follicles, nails and mustaches)

62. Majja_vaha srotas

Parva shoola (Pain in the Interphalangeal joints) (1)

Bhrama (Vertigo/Giddiness) (2)

20

Moorchh (Syncope) (3)

Mithyajnana (Illusion) (4)

63. Shukra_vaha srotas

Klaivya (Sterility / impotence) (1)

Aharshan (Loss of erection) (2)

Garbha pata (Abortion) (3)

Santam Vikriti (Congenital deformity of the children) (4)

64. Manovaha srotas

Manovibramsha (1)

Budhivibramsha (2)

Sanjna Vibhramsha (3)

Smritivibhramsha (4)

Bhaktivibhramsha (5)

Sheelavibhramsha (6)

Chesta Vibhramsha (7)

Acharavibhramsha (8)

65. Artava vaha srotas

Anartava (Amenorrhoea) (1)

Vandhyatva (Sterility) (2)

66. Mutra vaha srotas

Bahumutra (Polyuria) (1)

Atibadhata (Urination with obstruction) (2)

Prakop-mutra (Defective Urination / Difficulty (3)in micturition)

21

Alpaalpa (Scanty urination) (4)

Aabhikshna (Constant / repeated urination) (5)

Bahulamutrata (Urine with prostatic secretion) (6)

Sashool amutrata (Painful micturition) (7)

67. Pureeshavaha srotas

Alpaalpa Pureesha (Scanty defecation) (1)

Sashoola Pureesha (Painful defecation) (2)

Atidrava Pureesha (Diarrhoea) (3)

Atigrathita yukta Pureesha (Scybala) (4)

68. Sweda vaha srotas

Aswedan (Loss of perspiration) (1)

Atiswedana (Profuse sweating) (2)

Parushya (Roughness of the skin) (3)

Lomaharsha (Thrill) (4)

Aangaparidaha (Burning sensation in the body) (5)

Date: _______________ Signature of the investigator: ______________________

22



CASE REPORT FORM III - CLINICAL ASSESSMENT

(0, 15, 30 days)

1. Centre: ………………..……….






SYMPTOMS: The following clinical symptoms (Serial no 1-5) along with question on beta–2 agonist use and another on FEV1% predicted are noted as per ACQ.

1. AIRE (ACQ)* ASTHMA CONTROL QUESTIONN

a. On average, during the past week, how often were you woken by your asthma during thenight?

i. Never (0)

ii. Hardly ever (1)

iii. A few times (2)

iv. Several times (3)

v. Many times (4)

vi. A great many times(5)

vii.Unable to sleep because of asthma’

b. On average, during the past week, how bad were your asthma symptoms when you wok upin the morning?

i. No symptoms (0)

23

ii. Very mild symptoms (1)

iii. Mild symptoms (2)

iv. Moderate symptoms (3)

v. Quite severe symptoms (4)

vi. Severe symptoms (5)

vii.Very severe symptoms (6)

c. In general, during the past week, how limited were you in your activities because of yourasthma?

i. Not limited at all (0)

ii. Very slightly limited (1)

iii. Slightly limited (2)

iv. Moderately limited (3)

v. Very limited (4)

vi. Extremely limited (5)

vii.Total limited (6)

d. In general, during the past week, how much shortness of breath did you experience becauseof your asthma?

i. None (0)

ii. A very little (1)

iii. A moderate amount (2)

iv. Quite a lot (3)

v. A great deal (4)

vi. A very great deal (5)

e. In general, during t he past week, how much of t he time did your wheeze?

i. Not at all (0)

24

ii. Hardly any of the time (1)

iii. A moderate amount of the time (2)

iv. A lot of the time (3)

v. Most of the time (4)

vi. All the time. (5)

f. On average, during the past week, how many puffs of short-acting bronchodilator (e.g.Ventorlin) have you used each day?

i. None (0)

ii. 1-2 puffs most days (1)

iii. 3-4 puffs most days (2)

iv. 5-8 puffs most days (3)

v. 9-12 puffs most days (4)

vi. 13-16 puffs most days (5)

vii.More than 16 puffs most days.(6)

To be completed by a member of the clinic staff.

8. FEV1 prebronchodilator……………….. 0 > 95% predicted

1 95-90%

FEV1 % predicted…………………….. 2 89-80%

3 79-70%

FEV1 % predicted………………….… 4 69-60%

5 59-50%

6 <50% predicted

PHYSIOLOGICAL ASSESSMENT (To be monitored fortnightly.)

9. Blood pressure Systolic (mm Hg.)/Diastolic (mmHg.):

10. Pulse rate (per minute)

11. Temperature

25

12. Respiratory rate (per minute)

13. FEVI (Spirometery) —————————————————— (% 0f predicted value)

14. Overall clinical assessment by the Doctor on the basis of ASTHMA CONTROL

QUOTIONNAIRE

Good control (1) Poor control (2)

15. VAS (Visual Analogous Scale)

16. Overall impression of well-being by the Subject:

Improved (1) No change (2) Deteriorated (3)

17. Status of the patient:

Continuing (1)

Drop out (2)

Reason a) self withdrawn by the patient (1)

b) Physician wants to withdrawn the patient (2)

Date: ______________ Signature of Investigator __________________

Red Zone (1) Yellow Zone (2) Green Zone (3)

Serious trouble with Mild Trouble with No Trouble with Asthma Asthma Asthma

26



CASE REPORT FORM IIIA - ADVERSE EVENTS RECORD FORM

(0, 15, 30 days)

1. Centre: ………………..……….






ADVERSE EVENTS

Do the patients have any symptoms with medication in trial groups? Yes (1) No (0)

Please complete all sections & enter l approximate information in numbers in open boxes

1 2 3 4

AdverseExperience

Date started

Date

27

Time

Date stopped

Pattern

Isolated-1

Intermittent-2

Continuous-3

Severity

Mild-1

Moderate-2

Severe-3

*Mild-No interference with usual activity. *Moderate-Significant interference with usualactivities. *Severe-Prevents usual activities.

Serious*

Yes-1

No-2

Serious ADE is defined as fatal, life-threatening, permanently, disabling requires inpatienthospitalization or as a congenital anomaly, cancer or overdose. If yes, please till seriousAdverse experiences report form provided. In case of Serious adverse event sponsor shouldbe informed immediately telephonically.

Relationship to studymedication

Unrelated-1

Possible-2

Probable-3

28

Unrelated: A reaction that does not follow a reasonable temporal sequence from theadministration of the drug; or a known adverse reaction pattern of the suspected drugscould have been produced by the patients clinical stage, intermittent illness, trauma, accidentsetc:

Possible: follows a reasonable temporal sequence from administration of the drug; follows aknown response pattern to the suspected drug but could have been produced by the patientsclinical stage or other modes of therapy administered to the patients;

Probable: follows a reasonable temporal sequence from administration of the drug; follows aknown response pattern to the suspected drug; that could not be reasonably explained by theknown characteristics of the patients clinical state.

29



FORM IV– LABORATORY INVESTIGATIONS

(Before and after the treatment except Sl.No.23 which is to be done at

‘0’ week and Kidney, Liver function tests 0th, 15th and 30th day only)

1. Centre: ………………..……….






Urine Examination

7. Routine____________

8. Microscopic___________

Blood Examination

9. DC: P (%) ________ L (%) ________ E (%) ________ M (%) ________B (%) _______

10. Hb (g/dl) _________.

11. ESR (1st hour.)(mm) __________

12. Blood Sugar:

Fasting (mg./dl) _______________

PP. (mg. /dl) _______________

13. Uric acid (mg./dl) _____________

30

Kidney function tests (Sl.No.14 & 15)

14. B. Urea (mg. /dl) _______________

15. S. Creatinine (mg. /dl) ______________

Liver function tests (Sl.No.16 to 22)

16. Total proteins (g. /dl) _______________

17. Albumin (g. /dl) _______________

18. Globulin (g. /dl) _______________

19. A/G Ratio _______________

20. S. Bilirubin (mg. /dL)

Total

Direct

Indirect

21. SGPT. (IU/L)

22. SGOT (IU/L)

23. Alk. Phosphates (KA units) _______________

24. X-ray chest PA View (‘0’ WEEK only)

25. ECG (0, 4 week & if symptoms suggest sos)

26. Any other Remarks _________________________________________________

Date: ________________ Signature of the Investigator: _______________________

31

Drug: Study Code:


ASSESSMENT OF SAFETY AND THERAPEUTICEFFICACY OF SHIRISHADI KWATHA IN THE

MANAGEMENT OF MILD PERSISTENT ASTHMA(TAMAKA SHWASA)


32

Blank

33


ASSESSMENT OF SAFETY AND THERAPEUTIC EFFICACY OF SHIRISHADIKWATHA IN THE MANAGEMENT OF MILD PERSISTENT ASTHMA

(TAMAKA SHWASA)

References

1. Davidson’s Principle and Practice of Medicine 19th Edition pages 513-521

2. Charaka Samhita, Chikitsa Sthana, Hikka swasha, Chapter–17, Vidyotini Hindi Vyakhya by Pt. Kashinath,Choukhamba Orientalia, Varanasi

3. Ambika Dutta Sashtri(1989) Susruta samhita (text with Hindi commentary), Uttara Tantra Chapter 51, VIIthEdition Chaukhamba Sanskrit Series Office, Varanasi.

4. Harrison’s Principle of Internal medicine: 15th Edition pages 1456-1460

5. Annual Reports, P.R.U., Haffkine Institute, Bombay

6. Annual Report, P.R.U., L.H.M.C., New Delhi.

I. BACKGROUND

Tamaka Shwasa1 (Bronchial asthma) is prevalent all over the world. It is characterizedby chronic airway inflammation and increased airway responsiveness resulting in symptoms ofwheeze, cough, chest tightness and dyspnoea. It is also functionally characterized by the airflowlimitations usually reverses spontaneously or with treatment. The available treatment in modernmedical science like bronchodilators, steroids even in the form of inhalers and leukatriens modifiershave made tremendous success in providing instant or symptomatic relief in Bronchial asthma. Butthere is recurrent acute exacerbation and remissions and treatment has many side effects likenausea, vomiting, tremor, huskiness of voice, disturbance of hypothalamus – pituitary –adrenal axis.

In Ayurveda, Shireeshadi kwatha (3) which has been in practice as well as has shownanti-asthmatic effect in the clinical studies conducted in BHU, Varanasi & in clinical units of CentralCouncil for Research in Ayurveda and Siddha, Department of ISM & H, Ministry of Health &Family Welfare, New Delhi.

The toxicity studies done at the Industrial Toxicology Research Center(CSIR), Lucknow,December, 2002 report showed no acute and sub-acute toxicity of Shirisadi kwath at the dose of2500 mg. per Kg. Single dose (acute oral) and 200 ml. per kg. per day (subacute oral 1ml=0.5mg.) in mice.

34

II. OBJECTIVE

Primary Objective:

To evaluate the comparative efficacy of Shireeshadi kwatha & sustained-releasetheophylline in the mild persistent asthma.

Secondary Objective:

To evaluate the safety of Shireeshadi kwatha in the patients of mild persistent asthma.

III. CENTRE: CCRAS centers in collaboration with other centers

IV. SAMPLE SIZE AND METHODS

Sample Size: 250 (125 patients in each group)

Treatment:

A. Pre-treatment period:

There will be wash out period of two week (any oral bronchodilators should bewithdrawn gradually in both groups and patients in both groups will be allowed to take beta-2agonist inhalation s.os.).

B. Treatment period:

1. Trial drugs:

i) Shirishadi Kwatha(Decoction)

Shirishadi kwatha (50 gm.) contains Albizzia Lebbeck (Shirish) , Solanum Surattence(Kantkari), Adhatoda Vasica leaves (Vasa), Hedychium Spicatum (Shati) and equal in quantity.

Method of preparation of decoction: 50 gm. powder should be mixed in 400 ml ofwater and reduced to 100 ml. by boiling on low flame and constant stirring. It should then befiltered.

Dose & Duration: 100 ml in three divided doses daily for ninety days

2. Control Drug: theophylline sustained release tablet.

Dose: 400mg orally after dinner once daily.

Salbutamol inhaler 100 mcg.2 puffs sos is allowed if patient may feel acute

Breathlessness in both groups in pretreatment & treatment period. If patients aveconstipation, patient can take Vyaghri Haritaki 3-6 gm. with lukewarm water.

Design of the study – randomized controlled clinical study.

35

Duration of the study – 3 months drug therapy.

Period of Study: 3 months drug treatment period. Total duration will be 1 years tocomplete the trial. Recruitment of the patients up to seven months, treatment period for threemonths in both groups and data will be analyzed in next two months.


1. Age between 18 years to 40 years.

2. Both the sexes with equal distribution with or without rhinitis.

3. Mild persistent cases of Asthma (as per WHO GINA Guideline) of duration more than 6months.

4. Asthmatics who meet reversibility criteria (15% improvement in FEV I after beta-2agonist inhalation).

5. Symptoms/exacerbation (Wheeze, cough and breathlessness) greater than weekly and lessthan daily in frequency.

6. Night symptoms > twice per month but less than once a week.

7. FEV1 > 80% of the predicted value.

8. Never smokers.


1. Mild intermittent, Moderated persistent, severe persistent to severe Asthma.

2. FEV<80%.


4. Dyspnoea due to other disease like Left ventricular failure, COPD (Chronic Bronchitis,Emphysema), Upper respiratory tract obstruction, Bronchiectasis, cases of tuberculosis,interstitial lung disease/occupational Lung disease, tropical pulmonary eosinophilia, Lofflers disease & Allergic Bronchopulmonary Aspergillosis etc

5. Diabetes Mellitus and Hypertension.




9. Patient who need Salbutamol inhaler daily.

36


During the course of the trial treatment, if any serious condition or any serious adverseevents which requires urgent treatment or if patients himself want to withdraw from the study, suchsubjects may be withdrawn from the trial and managed by the Principal Investigator accordingly.


The full details of history and physical examination of the patients will be recorded as per theproforma (Forms I & IA). Clinical and physiological assessment will be done before treatmentand fortnightly during treatment period and at the end of the treatment. The laboratoryinvestigations will be carried out as per recorded in the proforma.


Data collected on scores of ACQ (ANNEX-1) & VAS (ANNEX-2) based on whichprogress of treatment will be analyzed using appropriate statistical tools.


The assessment of progress & outcome of treatment are assessed on the basis ofimprovement in the score of ASTHMA CONTROL QUESTIONNAIRE (Anexxure-1) and VAS(ANNEX-2) and safety evaluation will be made on the basis of serial recording of the adverseevents and Liver and Kidney function tests as per recorded in the proforma II B and III.

XI. TRIAL MONITORING AND DATA ANALYSES

The monitoring of progress of the trial and data analysis will be undertaken by CCRAS,Hqrs., New Delhi.

XII. ETHICAL REVIEW

Each Institutional Ethical Committee (IEC) of participating Center’s should give clearancecertificate before the project is initiated. Patient’s information sheet and informed consent formshould be submitted along with project proposal for approval by IEC. Both should be maintainedin duplicate with one copy given to the patient at the time of entry to the trial. The study will beconducted in accordance with Good Clinical Practice. This incorporates principles laid down inthe Declaration of Helsinki.


A consolidated amount of Rs…../- per visit i.e., on the 1st day of recruitment afterscreening, 15th, 30th, 45th, 60th, 75th and 90th days (7 times).


Short-term two-day training will be provided to the Investigators and Laboratory

37

personnel involved in the multi-centric trial at CCRAS Hqrs. and Central Research Institute (Ay.),New Delhi. The investigators and technicians will be detailed about the clinical trial conduct andlaboratory procedures in order to maintain the uniformity.



38






Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “Assessment of Safety & Therapeutic Efficacy of Shireeshadi kwatha in themanagement of Mild Persistent Asthma (Tamaka Swasa).





Relationship ___________________________________


39


ASSESSMENT OF SAFETY& THERAPEUTIC EFFICACY OF SHIRISHADIKWATHA IN THE MANAGEMENT OF MILD PERSISTENT ASTHMA

(TAMAKA SWASA)



The available treatment for bronchial asthma in modern medical science like broncho-dilators, steroids even in the form of inhalers have made tremendous success in providing instantor symptomatic relief but there is recurrent acute exacerbation and remission. In Ayurveda, manydrugs seem to possess a anti asthmatic effect of which Shirishadi Kwatha that have been inpractice as well as have shown anti-asthmatic effect have been taken up for the study.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 3 months to complete. During thisperiod, you are expected to visit the hospital 6 times for clinical and physiological assessment.

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination, ECG and an X-ray, Blood and urine samples will also be taken. This is tomake sure that you are eligible for the study.

If you are found eligible, you would be put on trial treatment for 3 months.

At each visit, you will be supplied with sufficient quantities of drugs to last untilyour next visit. If any adverse reactions like skin allergy, nausea, vomiting andpalpitation/tremor etc., noticed during the treatment period, this should be noticed to thePrinciple Investigator.


40



(TAMAKA SWASA)

CASE REPORT FORM I - SCREENING

BEFORE TREATMENT


1. Centre: ………………..……….


3. Name of the person: ………………………………........…………………………………



6. Address Permanent postal address with phone number and email if any.______________________________________________________________________________________________________________________________________________


7. Age between 18 years to 40 years

8. Both the sexes with equal distribution with or without rhinitis.

9. Mild persistent cases of Asthma (as per WHOGINA Guideline) of duration more than 6 months.

10. Asthmatics who meet reversibility criteria(15% improvement in FEV I after Beta-2 agonist inhalation.)

11. Symptoms/exacerbation (Wheeze, cough and breathlessness)greater than weekly and less than daily in frequency.

12. Night symptoms > twice per month.

13. FEV1 > 80% of the predicted value.

41

14. Ever smoker.


15. Mild intermittent, Moderated persistent, severepersistent to severe Asthma.

16. FEV<80%


18. Dyspnoea due to other disease like Left ventricularfailure, COPD (Chronic Bronchitis, Emphysema),Upper respiratory tract obstruction, Bronchiectasis,cases of tuberculosis, interstitial lung disease/occupationalLung disease, tropical pulmonary eosinophilia etc.

19. Uncontrolled Diabetes Mellitus and Hypertension.

20. Any other systemic disorder



23. Asthmatics that need daily Salbutamol inhaler.

A patient is eligible for admission to the trail


Date: ____________ Signature of the Investigator______________

42



(TAMAKA SWASA)



1. Centre: ………………..……….









8. Occupation: Desk work(1) Field work (2) Student (3)

Housewife (4) Others (5)


9. Income per capita per month (in Rs.)

Less than Rs.5000/- (1) More than Rs.-5000/- (2)

Chief complaint with duration (if any) in months

Present (1) Absent (0) If present,then duration

10. Breathlessness

43

11. Paroxysm of breathlessness

12. Wheezing

13. Cough

14. Expectoration of sputum

15. Nasal symptoms

16. Tightness in chest

17. Night symptoms

Yes (1) No (0) No. of attackPer month

a). Breathlessness,

b). Wheezing

c). Awakening in the night)

Present (1) Absent (0) If present,then duration

18. Skin allergy

History of Present illness:

19. History of Nasal symptoms

Yes (1) No (0)

1. Sneezing

2. Running nose

3. Blocked nose

4. Post nasal drip

5. History of throat clearing

If yes then specify: ...............................................................................................

44

Treatment History

Yes (1) No (0)

20. Traditional/Homeopathic Medicine

21. Modern Medicine

History of Past illness:

Yes (1) No (0)

22. History of skin allergy

23. Repeated colds

If yes indicate frequency of attack in months……………………………..

24. Family History of Asthma Present (1) Absent (0)

If present then specify:

Parents (1) Sibling (2) Both (3)

Personal History:

25. Diet: Veg (1) Non-Veg (2)

26. Any food/drink aggravated the symptoms Yes (1) No (0)

If yes, specify: ……………………………………………

27. Sleep Satisfactory (1) Unsatisfactory (2)

28. Constipation No (0) Yes (1)

History of Environmental

Yes (1) No (0)

29. Tobacco smoking exposure

If yes specify whether it aggravated the symptoms or not: …………………………

45

30. Tobacco chewing

If yes specify: (a) Quantity _____________

(b) Total duration in years: _____________

31. Betel chewing

32. History of alcohol intake:

Occasional (1) : 1

Regular (2) : 2

Never (3) : 3

33. Prakriti:


Vata-Kaphaj(4) Vata-Pittaja (5) Pittaja-Kaphaja (6)

Sama (7)

Physical Examination

34. Height (cm): ____________

35. Weight (kg) ____________

36. B.M.I Weight (kg.) ____________Height (meters) 2

37. Pulse (per min) ____________

38. Blood Pressure (mm Hg) ____________

39. Body temperature (o F) ____________

40. Respiration rate (per min) ____________

41. Cyanosis ____________

42. Clubbing nails ____________

{ }

46

43. Edema ____________

Absent (0) Present (1)

44. Pallor

45. Lymphadenopathy

If present, specify General(1) Local (2)

(Area)__________

Systemic Examination

46. Respiratory System Normal(1) Abnormal (2)

Shape of chest:

Auscultation

Ronchi: Present (1) Absent (2)

47. CVS Normal (1) Abnormal (2)

If abnormal, details____________________________________________

48. Appetite Normal (1) Abnormal (2)

If abnormal, details ______________________________________________

Date: …………….. Signature of Investigator: ……………………………….....

47



(TAMAKA SWASA)

FORM III -CLINICAL AND PHYSIOLOGICAL ASSESSMENT

(0, 15, 30, 45, 60, 75, 90 days)

1. Centre: ………………..……….







SYMPTOMS: The following clinical symptoms (Serial no 1-5) along with question on beta–2 agonist use and another on FEV1% predicted are noted as per ACQ.

ASTHMA CONTROL QUESTIONNAIRE (ACQ)*

a. On average, during the past week, how often were you woken by your asthma during thenight?

i. Never (0)

ii. Hardly ever (1)

iii. A few times (2)

iv. Several times (3)

v. Many times (4)

vi. A great many times (5)

48

vii.Unable to sleep because of asthma’ (6)

* To be translated in Regional language

b. On average, during the past week, how bad were your asthma symptoms when you wok upin the morning?

i. No symptoms (0)

ii. Very mild symptoms (1)

iii. Mild symptoms (2)

iv. Moderate symptoms (3)

v. Quite severe symptoms (4)

vi. Severe symptoms (5)

vii.Very severe symptoms (6)

c. In general, during the past week, how limited were you in your activities because of yourasthma?

i. Not limited at all (0)

ii. Very slightly limited (1)

iii. Slightly limited (2)

iv. Moderately limited (3)

v. Very limited (4)

vi. Extremely limited (5)

vii.Total limited (6)

d. In general, during the past week, how much shortness of breath did you experience becauseof your asthma?

i. None (0)

ii. A very little (1)

iii. A moderate amount (2)

49

iv. Quite a lot (3)

v. A great deal (4)

vi. A very great deal (5)

e. In general, during the past week, how much of the time did your wheeze?

i. Not at all (0)

ii. Hardly any of the time (1)

iii. A moderate amount of the time (2)

iv. A lot of the time (3)

v. Most of the time (4)

vi. All the time. (5)

f. On average, during the past week, how many puffs of short-acting bronchodilator (e.g.Ventorlin) have you used each day?

i. None (0)

ii. 1-2 puffs most days (1)

iii. 3-4 puffs most days (2)

iv. 5-8 puffs most days (3)

v. 9-12 puffs most days (4)

vi. 13-16 puffs most days (5)

vii.More than 16 puffs most days. (6)

* To be completed by a member of the clinic staff.

8. FEV1 prebronchodilator…………………..…… 0 > 95% predicted

1 95-90%

FEV1 % predicted….…………….……........ 2 89-80%

3 79-70%

50

FEV1 % predicted………………………...... 4 69-60%

5 59-50%

6 <50% predicted

PHYSIOLOGICAL ASSESSMENT (To be monitored fortnightly.)

9. a. Blood pressure

i. Systolic (mmHg.)

ii. Diastolic (mmHg.)

b. Pulse rate (per minute)

c. Temperature

d. Respiratory rate (per minute)

e. FEVI (Spirometery): ___________________________

(% 0f predicted value)

10. Overall clinical assessment by the Doctor on the basis of ASTHMA CONTROLQUOTIONNAIRE

Good control (1) Poor control (2)

11. VAS (Visual Analogous Scale)



51



13.. Status of the patient:

Continuing (1)

Drop out (2)

Reason a) self withdrawn by the patient (1)

b) Physician wants to withdrawn the patient (2)


52



(TAMAKA SWASA)

CASE REPORT FORM III A - ADVERSE EVENTS RECORD

(0, 15, 30, 45, 60, 75, 90 days)

1. Centre: ………………..……….







ADVERSE EVENTS

8. Does the patient have any symptoms with medication in trial group? Yes(1) No(0)


1 2 3 4

Adverse

Experience

53

Date started

Date

Time

Date stopped

Pattern

Isolated-1

Intermittent-2

Continuous-3

Severity

Mild-1

Moderate-2

Severe-3

*Mild-No interference with usual activity. *Moderate-Significant interference with usual

activities. *Severe-Prevents usual activities.

Serious*

Yes-1

No-2

Serious ADE is defined as fatal, life-threatening, permanently, disabling requires inpatient

hospitalization or as a congenital anomaly, cancer or overdose. If yes, please till serious

Adverse experiences report form provided. In case of Serious adverse event sponsor should

be informed immediately telephonically.

54

Relationship

to study

medication

Unrelated-1

Possible-2

Probable-3

Unrelated: A reaction that does not follow a reasonable temporal sequence from the

administration of the drug; or a known adverse reaction pattern of the suspected drugs could

have been produced by the patients clinical stage, intermittent illness, trauma, accidents etc:

Possible: follows a reasonable temporal sequence from administration of the drug; follows a

known response pattern to the suspected drug but could have been produced by the patients

clinical stage or other modes of therapy administered to the patients;

Probable: follows a reasonable temporal sequence from administration of the drug; follows a

known response pattern to the suspected drug; that could not be reasonably explained by the

known characteristics of the patient's clinical state.

55



(TAMAKA SWASA)

CASE REPORT FORM IV – LABORATORY INVESTIGATIONS

(Before and after the treatment except Sl.No.23 which is to be done at ‘O’week and Kidney, Liver function tests O, 6th and 12th week only.)

1. Centre: ………………..……….





6. Date of Assessment ___________________

7. Urine Examination

Routine____________ Microscopic___________

8. C (Cells/Cmm.)_____________________

9. DLC: P(%)______ L(%)______ E (%)______ M (%)______ B (%)______

10. Absolute Eosinophil count ————————————

11. Hb (g/dl): __________

12. ESR (1st hour.)(mm) __________

13. Blood Sugar:

Fasting (mg./dl) __________

PP. (mg./dl) __________

14. Uric acid (mg./dl)_____________

56

Kidney function tests (Sl.No.14 & 15)

15. B. Urea (mg./dl) _______________

16. S. Creatinine (mg./dl) _______________

Liver function tests (Sl.No.16 to 22)

17. Total proteins (g./dl) _______________

18. Albumin (g./dl) _______________

19. Globulin (g./dl) _______________

20. A/G Ratio _______________

21. S. Bilirubin(mg./dL)

Total: ___________

Direct: ___________

Indirect: ___________

22. SGPT. (IU/L)

23. SGOT (IU/L)

24. Alk. Phosphates(KA units) _______________

25. X-ray chest & PNS(‘0’ WEEK only)

26. ECG(0, 12 WEEK & if symptoms suggest SOS)

27. Any other Remarks: ______________________________________________

Date: ……………. Signature of the Investigator: ………………………........

Place: ……………

57

PROTOCOL FOR ASSESSMENT OF THERAPEUTIC EFFICACY OFSHIRISHADI KWATHA IN THE MANAGEMENT OF TAMAKA SHWASA

(BRONCHIAL ASTHMA)

Annexure-1: ASTHMA CONTROL QUESTIONNAIRE 1

SYMPTOMS: The following clinical symptoms (Serial no 1-5) alongwith question on beta –2

agonist use and another on FEV1% predicted are noted as per ACQ.

Please answer Question 1-6

1. On average, during the past week, how often were you woken by your asthma during thenight?

0. Never (0)

1. Hardly ever (1)

2. A few times (2)

3. Several times (3)

4. Many times (4)

5. A great many times (5)

6. Unable to sleep because of asthma’ (6)

2. On average, during the past week, how bad were your asthma symptoms when you wokeup in the morning?

0 No symptoms (0)

1 Very mild symptoms (1)

2 Mild symptoms (2)

3 Moderate symptoms (3)

4 Quite severe symptoms (4)

5 Severe symptoms (5)

6 Very severe symptoms (6)

3. In general, during the past week, how limited were you in your activities because of yourasthma?

0 Not limited at all (0)

58

1 Very slightly limited (1)

2 Slightly limited (2)

3 Moderately limited (3)

4 Very limited (4)

5 Extremely limited (5)

6 Total limited (6)

4. In general, during the past week, how much shortness of breath did experience because ofyour asthma?

0. None (0)

1. A very little (1)

2. A moderate amount (2)

3. Quite a lot (3)

4. A great deal (4)

5. A very great deal (5)

5. In general, during the past week, how much of the time did your wheeze?

0. Not at all (0)

1. Hardly any of the time (1)

2. A moderate amount of the time (2)

3. A lot of the time (3)

4. Most of the time (4)

5. All the time. (5)

6. On average, during the past week, how many puffs of short-acting bronchodilator (e.g.Ventorlin) have you used each day?

0. None (0)

1. 1-2 puffs most days (1)




59


6. More than 16 puffs most days.

To be completed by a member of the clinic staff.

7. FEV1 prebronchodilator……………...... 0 > 95% predicted

1 95-90%

FEV1 % predicted…….……….....… 2 89-80%

3 79-70%

FEV1 % predicted………………...... 4 69-60%

5 59-50%

6 < 50% predicted

Patients are asked to recall their symptoms & short-acting beta-2 agonist use during the previousweek. All seven questions as mentioned in ACQ are scored on a seven point scale (0=goodcontrol,6=poor control) ,and the overall score is the mean of seven responses.

1: Elizabeth F.Juniper, Paul M et al. Am J Respir Crit Care Med Vol 162 pp1330-34, 2000

60

PROTOCOL FOR ASSESSMENT OF THERAPEUTIC EFFICACY OFSHIRISHADI KWATHA IN THE MANAGEMENT OF TAMAKA SHWASA

(BRONCHIAL ASTHMA)

Annexure-II

Name of Centre: ___________________________________________________________

Name: ___________________________________ Age: _________ Gender: __________

Date:-________ C.R No. _________

VISUAL ANALOGUE SCALE (VAS)1



Scale: 100 mm long 2

Green zone 80 mm-100 mm “No trouble with asthma” 2

Yellow zone 79 mm-50 mm “Mild trouble with asthma” 2

Red zone Below 50 mm “Serious trouble with asthma”2

References

1. J. Asthma 2003; 40:27-39

2. National Heart, Lung, and Blood Institute, Publication No.97-4051, Expert Panel Report II, 1997.

61

GASTRO INTESTINAL SYSTEM

SEC

TIO

N - II

62

Blank

63

Drug: Study Code:


CLINICAL VALIDATION OF BILWAMAJJA CHURNAIN KAPHAJA PRAVAHIKA (IBS)


64

Blank

65

I. BACKGROUND

Kaphaja Pravahika1 (vis-à-vis Irritable bowel syndrome) is a disease of thePurishavaha srotas, caused due to excessive intake of unctuous and heavy foods and ischaracterised by the association of excessive mucous in the stool along with abdominal pain,discomfort and bloating.

According to allopathic system of medicine Irritable bowel syndrome (IBS) is a blanketterm for a variety of diseases causing discomfort in the gastro-intestinal tract. It is a functionalbowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration ofbowel habits in the absence of any organic cause. In some cases, the symptoms are relieved bybowel movements. Certain psychological conditions are also more common in those with IBS.Treatments for IBS includes attempt to relieve symptoms, including dietary adjustments, medicationand psychological interventions. Patient education and a good doctor-patient relationship are alsoimportant.

Owing to the complications and adverse effects of current modern medication to managesuch condition, need is felt for search of safe /effective Ayurvedic oral dosage forms with scientificparameters. Keeping the gravity of the situation and the public health needs in view, the council hasinitiated scientific studies on Bilwamajja Churna, a promising herbal drug that is being successfullyprescribed by Ayurvedic physicians without any side effects since centuries in Kaphaja Pravahika(IBS).

II. OBJECTIVE

To assess the effect of Bilwamajja Churna in reducing the signs and symptoms of KaphajaPravahika (IBS)


CLINICAL VALIDATION OF BILWAMAJJA CHURNA IN KAPHAJAPRAVAHIKA (IBS)

References

1. Charaka Samhita, Chikitsa Sthana, Chapter–17, Vidyotini Hindi Vyakhya by Pt. Kashinath, ChoukhambaOrientalia, Varanasi

2. Ambika Dutta Sashtri (1989), Susruta samhita (text with Hindi commentary), Uttara Tantra Chapter 40,VIIth Edition Chaukhamba Sanskrit Series Office, Varanasi.

3. Harrison’s Principle of Internal medicine: 17th Edition, Vol – 1, Page: 970

66

III. CENTERS

CCRAS identified Centers


No. of Groups : One

Sample size : 30 Subjects per center

Trial Drug /Dosage /Duration : Bilwamajja churna 3 gms twice daily afterfood for 30 days with warm water for 30days and follow-up for another 15 dayswithout medicine.

Design of the study : Open trial

Total period of the study : One year

Follow up study: : For a period of 15 days at the interval of7 days after completion of the therapy.


1. Age between 15 and 60 years

2. History of frequent passing of little quantity of stool along with mucous and tenesmus.

3. The frequency of passing of stool should be 3 times or more in 24 hours.

4. Stool examination should be positive either with E.H. cyst or E.coli or both.


1. Age below 15 years and above 60 years.

2. Stool test negative for E.H. cyst and/or E.coli.

3. Mixed infection with other parasites like round worms, hook worms etc.

4. Complicated with tuberculosis, malignancy or hepatic abscess.

5. Associated with other grave systemic diseases like cardiac disorders, jaundice, diabetesmellitus etc.


During the course of the trial, if any serious condition or any serious adverse events whichrequires urgent treatment or if subjects themselves want to withdraw from the study, such subjectsmay be withdrawn from the trial.

67


The full details of screening and history along with physical examination of the subjects willbe recorded as per case report form I & II respectively. Clinical and physiological assessment inform III and laboratory investigations in form IV will be done at 0, 15th & 30th days.Consolidated data on periodical observation will be recorded in case report form-V.

IX. ASSESSMENT CRITERIA :

Sl. Frequency of passing of stool Grade Score

No. motions per 24 hours

1 Up to Two Zero 0

2 3 - 5 I 2

3 6 - 8 II 4

4 9 & above III 6

Sl. Tenesmus / Abdominal pain Grade Score

1 Mild (Tolerable by the patient) Zero 0

2 Moderate (Twisting pain in abdomenbut not rolling type) I 2

3 Severe (Un tolerable and rolling type) II 4

Sl. Bloating Grade Score

1 Present Zero 0

2 Absent I 2

Sl. Stool examination for parasite Grade Score(E.H / E.Coli)

1 Present Zero 0

2 Absent I 2

68

X. STATISTICAL ANALYSIS:

Data on clinical symptoms and objective tests before and after the treatment will betabulated and analyzed using appropriate statistical tools. However the data of each case will haveto be communicated on completion of trial therapy to the Statistical Officer of CCRAS through e-mail ([email protected]).

XI. TRIAL MONITORING AND DATA ANALYSIS:

CCRAS, Hqrs, New Delhi will undertake the monitoring of progress of the trial and dataanalysis.

XII. ETHICAL REVIEW:

A. Institutional Ethical Committee (IEC): The proposal will be placed beforeInstitutional Ethical Committee (IEC) of trial center for getting clearance certificate before theproject is initiated. Patient’s information sheet and informed consent form will be submitted alongwith project proposal for approval by IEC.

B. Data and safety monitoring board: A Data and safety monitoring board (DSMB)at Hqrs will carefully monitor the data and side effects during the period of study and put in aplace where by prompt reporting of adverse events occur and take appropriate steps in case ofany adverse events occur. The data will be reviewed for every 20 participants included into thestudy and administered the trial drugs. The research team will report immediately to the PI andData Monitoring Board, any life threatening conditions whether they are perceived to be studyrelated or not. The Board decides whether the adverse effects warrant discontinuation of the studyprotocol. Protocols will be written and approved for the treatment of study related adverse eventsabout the clinical trial conduct and laboratory procedures in order to maintain the uniformity.


A consolidated amount of Rs……./- per visit will be paid to subject selected in the study.


Short-term two-day training will be provided to the Investigators and Laboratorypersonnel involved in the multicentric trial at CCRAS Hqrs. and Central Research Institute (Ay.),New Delhi. The investigators and technicians will be detailed about the clinical trial conduct andlaboratory procedures in order to maintain the uniformity.


1. Stool:

Routine & Microscopic

E.H. Cyst & E. Coli

69

Mucous

Occult blood

Ingested Vegetable particles

2. Urine:

Routine & Microscopic

3. Blood:

TLC

DC

Hb%

ESR

FBS

Mx Test

70







Name: ____________________________

CONSENT BY SUBJECT

I have been informed to my satisfaction, by the attending physician about the purpose ofthe clinical trial and the nature of drug treatment and follow-up, including the laboratoryinvestigations to be performed to monitor and safeguard my body functions.

I am also aware of my right to opt out of the trial at any time during the course of the trialwithout having to give the reasons for doing so. I am willing to undergo any risk for inclusion inthis study.

I, exercising my free power of choice, hereby give my consent to be included as a subjectin the “Clinical validation of bilwamajja churna in kaphaja pravahika (IBS)”





Relationship ___________________________________


71





Kaphaja Pravahika (which is consider as Irritable bowel syndrome as per allopathicsystem of medicine) is a disease of the Purishavaha srotas, caused due to excessive intake ofonctuous and heavy foods and is characterised by the association of excessive mucous in the stoolalong with abdominal pain, discomfort and bloating.

According to allopathic system of medicine Irritable bowel syndrome (IBS) is a blanketterm for a variety of diseases causing discomfort in the gastro-intestinal tract. It is a functionalbowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration ofbowel habits in the absence of any organic cause. In some cases, the symptoms are relieved bybowel movements. Certain psychological conditions are also more common in those with IBS.

Owing to the complications and adverse effects of current modern medication to managesuch condition, need is felt for search of safe /effective Ayurvedic oral dosage forms with scientificparameters. Keeping the gravity of the situation and the public health needs in view, the council hasinitiated scientific studies on Bilwamajja Churna, a promising herbal drug, which is beingsuccessfully prescribed by Ayurvedic physicians without any side effects since centuries in KaphajaPravahika (IBS).


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately one month (30 days). Duringtreatment period, you are expected to visit the hospital three times i.e. on 0,7th, 15th and 30th dayfor clinical and physiological assessment.

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination, required objective tests and laboratory investigations will also be done.

If you are found eligible, you would be put on trial treatment for 30 days.

At each visit, you will be supplied with sufficient quantities of drugs to last until your nextvisit. If any adverse reactions like skin allergy, nausea, vomiting and palpitation/tremor etc. arenoticed during the treatment period, this should be brought to the notice of the PrincipalInvestigator.


72




BEFORE TREATMENT


1. Centre: ………………..……….





6. Address ……………………………………..………………………………………



2. History of frequent passing of little quantity of stool

3. along with mucous and tenesmus.

4. The frequency of passing of stool should be 3 times

5. or more for 24 hours

6. Stool should be positive either with E.H. cyst or

7. E. Coli or both


8. Age below 15 years and above 60 years

9. Stool test negative for E.H. cyst and/or E.coli

73

10. Mixed infection with other parasites like round worms,hook worms etc

11. Complicated with tuberculosis, malignancy or hepatic abscess.

12. Associated with other grave systemic diseases like cardiacdisorders, jaundice, diabetes mellitus etc



Date: __________________ Signature of the investigator: ___________________

74





1. Centre: ………………..……….


3. Sr. No. of the subject: …………………………...............…………………………………




7. Address ……………………………………..……………..........…………………………








10. Annual Income of the family Rs.

Less than Rs.60, 000/- (1) More than Rs.60, 000/- (2)

Total number of members sharing the income:

11. History of previous treatment

12. History of present illness:

75


13. Frequent passing of stool

14. Tenesmus

15. Passing of stool with mucous

16. Abdominal pain

17. Bloating

18. Alteration of bowel habits

19. Previous episodes

20. Onset of disease Acute (1) Chronic (2)

21. Treatment given so far:

Traditional Medicine (1) Modern Medicine(2)

PERSONAL HISTORY


23. Digestion (Agni) Proper (1) Improper (2)

24. Sleep Normal (1) Disturbed (2)


If yes, specify ……………………………………………………………………..

26. Bowel habit Regular (1) Irregular (2)

If irregular, specify …………………………………………………………………….



Sannipataj (7)

76

28. Manasa Prakriti: Sattva (1) Rajas (2) Tamas (3)

Sattva-Rajas(4) Rajas-Tamas(5) Sattva-Tamas (6)

Sama (7)




31. Body weight _________Kg. Height in cms. ____________

32. Body temperature ____________oF

33. Blood pressure (in sitting posture of right upper limb):

Systolic _______mm/Hg Diastolic _______mm/Hg




36. Pallor

37. Jaundice

38. Koilonychia

39. Lymphadenopathy



40. Digestive system


41. CNS

If abnormal, specify abnormalities_________________________

77

42. CVS with chest







i) Liver

ii) Spleen

Normal Abnormal




47. Anubandh dosha

48. Dushya (Involved) Rasa (1) Rakta(2) Mamsa (3)


Shukra (7) Ojas (8)

49. Srotas: Rasavaha (1) Raktavaha(2) Mamsavaha (3)

Medovaha(4) Annavaha(5) Purishavaha (6)

Mutravaha(7)

Date: _______________ Signature of the investigator: ________________________

78



CASE REPORT FORM III -PERIODICAL OBSERVATION AND CLINICALASSESSMENT

(On Day 0, 7th, 15th, 30th day)

Separate form should be used on each visit (Enter a � in the appropriate box)

1. Centre: ………………..……….


3. Sr. No. of the subject: ……………………………........………………………….………

4. Name ...................................................................... Age ..................... Sex .......................

5. Date of Assessment ..............................................................................................................

Chief complaints with duration (in days) Yes (1) No (0) if yes, Duration(in days)

6. Frequent passing of stool

7. Tenesmus

8. Passing of stool with mucous

9. Abdominal pain

10. Bloating

11. Alteration of bowel habits

12. Other symptoms ( if any)

Any other, specify______________________________________

Date: ______________ Signature of investigator___________________

79



(On Day 0, 7th, 15th, 30th day)

CASE REPORT FORM IV-PERIODICAL OBSERVATION AND LABORATORYASSESSMENT


1. Centre: ………………..……….






7. Date of Assessment

8. Stool examination

Routine Microscopic

Ova/Cyst

Mucous,

Vegitative cells


Routine Microscopic

Blood

10. TC (Cells/Cu. mm.): _______________

11. DC: P _____ (%) L _____ (%) E ______ (%) M _____ (%) B ______(%)

80

12. ESR (mm / 1st hour.) __________

13. Hb (g/dl) ____________________

Liver function tests

14. S. Bilirubin

• Total (mg/dl)

• Direct (mg/dl)

15. SGPT (IU/L)

16. SGOT (IU/L)

17. S. Alkaline phosphatase (U/L)

18. S. Proteins (Total) (g/dl)

• Albumin (g/dl)

• Globulin (g/dl)

Renal function tests

19. Blood urea (mg/dl)

20. S.Creatinine (mg/dl)

Specific Investigations:

21. Stool culture

22. Mx Test

23. FBS

Date: _____________ Signature of investigator _______________________

81



CASE REPORT FORM V-CONSOLIDATED DATA ON PERIODICALOBSERVATIONS


1. Centre: ………………..……….







Sl Subjective/ objective 0 day/BT 7th dayDt. 15th dayDt. 30th day/ATParameters Dt. Dt. Dt. Dt.

1. Frequent passing ofstool

2. Tenesmus

3. Passing of stool withmucous

4. Abdominal pain

5. Bloating

6. Alteration of bowelhabits

7. Adverse reactions

Burning sensation in Notabdomen applicable

Nausea Not applicable

82

Diarrhoea Not applicable

Skin rashes Not applicable

8. TC (Cells/Cu. mm.) Not applicable

9. DCLLLL P _____% P _____% P _____%L _____% Not L _____% L _____%E _____% applicable E _____% E _____%

10. ESR (mm / 1st hour.) Notapplicable

Sl Subjective/ 0 day/ 7th day 15th day 30th day/objective BT Dt. Dt. Dt. AT Dt.Parameters

11. Hb (g/dl)

12. Liver functiontests

13. S. Bilirubin

a. Total(mg/dl) Not Not

b. Direct applicable applicable(mg/dl)

14. SGPT (IU/L)

15. SGOT (IU/L)

16. S. Alkalinephosphatase(U/L)

17. S. Proteins(Total) (g/dl)

18. Albumin (g/dl)

19. Globulin (g/dl)

20. Renal functiontests

21. Blood urea Not Not(mg/dl) applicable applicable

83

22. S. Creatinine(mg/dl)

23. UrineExamination

Routine Notapplicable

Microscopic Notapplicable

24. StoolExamination

Occult Blood Not Notapplicable applicable

Ova/Cyst Not Notapplicable applicable

Mucous Not Notapplicable applicable

Vegetative Not Notcells applicable applicable

8. Overall clinical assessment


9. Overall impression of well being by the Subject:


10. Status of the subject:

Completed (1)

Drop out (2) Reason: _____________________________

Died (3) Cause: _______________________________

Date: ______________ Signature of investigator ______________

84

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85

Drug: Study Code:


MULTICENTRIC OPEN CLINICAL TRIAL OFPALASABEEJA CHURNA IN KRIMI ROGA

(GANDUPADA KRIMI)


86

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87

I. BACKGROUND

Krimi Roga (Intestinal nematode infections)1 is the most common ailment which affect onefourth to one third of the world’s population. Of these, the Gandupada Krimi (intestinalroundworm-Ascaris lumbricoides) is the most common. Worldwide, 1.4 billion people areinfected with a lumbricoides. While the vast majority of these cases are asymptomatic, infectedpersons may present with pulmonary or gastrointestinal complaints.

The rate of complications secondary to Ascariasis ranges from 11-67%, with intestinal andbiliary tract obstruction representing the most common serious sequelae. Although infection with Alumbricoides is rarely fatal, it is responsible for an estimated 8,000-100,000 deaths annually,mainly in children. Ascariasis predominates in areas of poor sanitation and is associated withmalnutrition, iron-deficiency anemia, and impairments of growth and cognition.

Owing to the gravity of the signs, symptoms and rate of complications caused by Ascaris,it is need to explore and re-establish the efficacy of classical drug Palashbeeja Churna in oraldosage form to treat the patients affected with Gandupada Krimi (A lumbricoides).

II. OBJECTIVES

1) To see the clinical efficacy of Palashbeeja Churna in the management of GandupadaKrimi Roga (Ascariasis).

2) Observe the clinical safety of Palashbeeja Churna in the subjects affected by theGandupada Krimi (A lumbricoides).


MULTICENTRIC OPEN CLINICAL TRIAL OF PALASABEEJA CHURNA INKRIMI ROGA (GANDUPADA KRIMI)

References

1. Charaka Samhita, Vimana Sthana Chapter– 7, Vidyotini Hindi Vyakhya by Vd. Ambikadatta Shastry,Choukhamba Orientalia, Varanasi

2. Harisson’s Principles of internal medicine, Volume-1, 14th Edition, International Editions, 1998, Publishedby McGraw-Hill CompaniesInc.pp1208-1209

3. Davidson’s Principles and practice of Medicine, 18th Edition, 1999, Published by Harcourt Brace andCompany, pp173-174

4. Diagnosis and Treatment of diseases in Ayurveda based on Ayurveda saukhyam of Todaranand, Part-IIby Bhagawan Dash & Lalit Kashyap, 1982, pp-286

5. Bhaisajya Ratnavali, Krimiroga Chikitsa Prakarana, Chaukhamba Sanskrit Samsthan, Varanasi

88

III. CENTRE

Identified CCRAS Institutes.


Sample size : 40 subjects per centre

Trial Drug /Dosage /Duration : Palashbeeja Churna 750 mg-3 gm(Dragee form) twice daily before meal forfifteen (15) days with honey.

Design of the study : Open observational

Total period of the study : 1 year (recruitment of Subjects up to theend of 6th Month, continuation of trialtherapy till end of 8th Month, last 4months for compilation of data andStatistical analysis)


1. Age between 5 to 20 years of either sex.

2. Presence of signs and symptoms caused by A. lumbricoids

3. Positive ova of Ascaris in the stool

4. No history of other parasitic infestation


1. Age less than 5 years and more than 20 years.

2. Negative ova of Ascaris in the stool

3. Other parasitic infestation like hook worm, giardia, EH cyst, etc.

4. Any concomitant disorder of the liver, kidneys, heart, lungs or others


During the course of the trial treatment, if any serious condition or any serious adverseevents which requires urgent treatment or if patients himself want to withdraw from the study, suchsubjects may be withdrawn from the trial.


The full details of screening, history and physical examination of the subjects will berecorded as per case report form I & II. Clinical and physiological assessment in form III and

89

laboratory investigations in forms IV A, B, C will be done at 0, 8th & 15th days respectively.Consolidated data on periodical observation will be recorded in case Report form V at 15th day.

IX. CRITERIA FOR ASSESSMENT

Changes in the signs and symptoms and absence of ova of Ascaris will be considered forassessing the outcome of the treatment on 8th and 15th day. The safety parameters (liver and kidneyfunction) will be assessed at 0 and 45th day.


Data on clinical symptoms and objective tests before and after the treatment will betabulated and analyzed using appropriate statistical tools. However, the data of each case will haveto be communicated on completion of trial therapy to the Statistical Officer of CCRAS through e-mail.



XII. ETHICAL REVIEW

A. Ethical Committee (IEC): The proposal will be placed before Ethical Committee(IEC) of trial center for getting clearance certificate before the project is initiated. Patient’sinformation sheet and informed consent form will be submitted along with project proposal forapproval by EC. Both will be maintained in duplicate with one copy given to the patient at thetime of entry to the trial.

B. Data and safety monitoring board: A Data and safety monitoring board (DSMB)at Hqrs. will carefully monitor the data and side effects during the period of study and put in aplace where by prompt reporting of adverse events occur. The data will be reviewed as every 20participants entered the study and administered the trial drugs. The research team will reportimmediately to the PI and Data Monitoring Board if, any life threatening conditions whether theyare perceived to be study related or not. The Board decides whether the adverse effects warrantdiscontinuation of the study protocol. Protocols will be written and approved for the treatment ofstudy related adverse events.


A consolidated amount of Rs.100/- per visit i.e., on the 1st day of recruitment afterscreening, 8th day, and 15th day. (3 times)

90


Short-term two-day training will be provided to the Investigators and Laboratorypersonnel involved in the multi-centric trial at CCRAS Hqrs. and Central Research Institute (Ay.),New Delhi. The investigators and technicians will be detailed about the clinical trial conduct andlaboratory procedures in order to maintain the uniformity.



91







Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “Multicentric open Clinical trial of Palasabeeja Churna in Krimi Roga

(Gandupada Krimi)”.





Relationship ___________________________________


92





Krimi Roga (Intestinal nematode infections) is the most common ailment which affect onefourth to one third of the world’s population. Of these, the Gandupada Krimi (intestinalroundworm-Ascaris lumbricoides) is the most common. Worldwide, 1.4 billion people areinfected with A lumbricoides. While the vast majority of these cases are asymptomatic, infectedpersons may present with pulmonary or gastrointestinal complaints.

The rate of complications secondary to Ascariasis ranges from 11-67%, with intestinal andbiliary tract obstruction representing the most common serious sequelae. Although infection with Alumbricoides is rarely fatal, it is responsible for an estimated 8,000-100,000 deaths annually,mainly in children. Ascariasis predominates in areas of poor sanitation and is associated withmalnutrition, iron-deficiency anemia, and impairments of growth and cognition.

Owing to the gravity of the signs, symptoms and rate of complications caused by Ascaris,it is need to explore and re-establish the efficacy of classical drug Palashbeeja Churna in oraldosage form to treat the patients affected with Gandupada Krimi (A lumbricoides).


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 15 days. During treatment period,you are expected to visit the hospital three times i.e. on 0, 8th, and 15th day for clinical andphysiological assessment.

Before you start treatment, during the first visit to the clinic, you will undergo acomplete physical examination, required objective tests and laboratory investigations willalso be done.




93




BEFORE TREATMENT


1. Centre: ………………..……….





6. Address ……………………………………..………………………………………



2. Presence of signs and symptoms caused by A. lumbricoids

3. Positive ova of Ascaris in the stool

4. No history of other parasitic infestation



6. Negative ova of Ascaris in the stool

7. Other parasitic infestation like hook worm, giardia,EH cyst, etc.

8. Any concomitant disorder of the liver, kidneys,heart, lungs or others.

94



If admitted, Sr. No. of the Subject: ________________

Date: __________________ Signature of the investigator: ____________________

95





1. Centre: ………………..……….






7. Address: Permanent postal address with phone number & E-mail if any.............................................................................................................................................................................................................................................................................................








10. Income per capita per month in Rs.: ____________________________


96

12. HISTORY OF PRESENT ILLNESS:


a) Jvara (Fever)

b) Vivarnata (Discoloration)

c) Shoola (Abdominal pain)

d) Hridroga(Cardiac disorders)

e) Sadana(Fatigue)

f) Bhrama(Giddiness)

g) Bhaktadwesha (Anorexia)

h) Atisara (Diarrhoea)

i) Swasa krichhrata (Dyspnea)

j) Hrillasa (Nausia)

k) Avipaka (Indigestion)

l) Anaha (Tympanitis)

m) Karshya (Cachexia)

n) Onset of disease Acute (1) Insidious (2)

o) Previous episodes Yes (1) No (0)

p) Duration of disease

q) Treatment given so far: Traditional Medicine (1) Modern Medicine (2)

13. PERSONAL HISTORY Yes (1) No (0)

a) Smoking

b) Non-Vegetarian diet

c) Alcoholic

97

c. Sharirika Prakriti: Vata (1) Pitta (2) Kapha (3)


Sannipataj (7)

14. PHYSICAL EXAMINATION

a) Built Lean (1) Medium (2) Heavy (3)

b) Gait Normal (1) Abnormal (2)

c) Body weight _________Kg.

d) Body temperature ____________oF

e) Blood pressure (in sitting posture of right upper limb):

Systolic_______mm/Hg Diastolic _______mm/Hg

f) Pulse rate__________/min. (Radial pulse of right upper limb)

g) Respiration rate _________/min.


h) Pallor

i) Jaundice

j) Koilonychia

k) Lymphadenopathy

15. SYSTEMIC EXAMINATION


a) CVS with chest


b) CNS

If abnormal, specify abnormalities_________________________

98

c) Digestive system


d) Uro-genital system


e) Respiratory system


f) Abdomen Palpable (1) Not palpable (2)

i) Liver

ii) Spleen

16. SAMPRAPTI (PATHOGENESIS)


a) Anubandhya dosha

b) Anubandh dosha

c) Avaraka dosha

d) Ksheen dosha

e) Ksheen dhatu Rasa (1) Rakta(2) Mamsa (3)


Shukra(7) Ojas (8)

f) Dushya (Involved) Rasa (1) Rakta(2) Mamsa (3)


Shukra(7) Ojas (8)

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CASE REPORT FORM III -PERIODICAL OBSERVATION AND ASSESSMENT

(On Day 0, 8th, and 15th)

Separate form should be used on each visit


1. Centre: ………………..……….


3. Sr. No. of the subject: ……………………………........…………………….……………




7. Date of Assessment: .............................................................................................................


8. Jvara (Fever)

9. Vivarnata (Discoloration)

10. Shoola (Abdominal pain)

11. Hridroga (Cardiac disorders)

12. Sadana (Fatigue)

13. Bhrama (Giddiness)

14. Bhaktadwesha (Anorexia)

15. Atisara (Diarrhoea)

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16. Swasakrichhrata (Dyspnea)

17. Hrillasa, Chhardi (Nausia, Vomiting)

18. Avipaka (Indigestion)

19. Anaha (Tympanitis)

20. Karshya (Cachexia)

21. Adverse reaction: Present (1) Absent (0)

i. Burning sensation in abdomen

ii. Nausea

iii. Diarrhoea

iv. Skin rashes

v. Any other, specify______________________________________

22. Overall clinical assessment:

Improved(1) No change(2) Deteriorated(3)


Improved(1) No change(2) Deteriorated(3)


Continuing (1)

Drop out (2) Reason: _____________________________

Died (3) Cause: _______________________________

Date: ______________ Signature of Investigator ___________________

101



(On Day 0)

FORM IV-A – LABORATORY INVESTIGATIONS


1. Centre: ………………..……….







Urine Examination

8. Routine: _____________

9. Microscopic: ______________

Stool examination:

10. Routine: _____________

11. Microscopic: ______________

12. Occult Blood: ___________

13. Ova/Cyst (Ova of A.lumbricoids): ____________

Blood

14. TC (Cells/Cmm.) _______________

102

15. DC - P _____ (%) L _____ (%) E ______ (%) M _____ (%) B ______(%)

16. ESR (mm / 1st hour.) __________

17. Hb (g/dl) ____________________


18. S. Bilirubin (mg/dl): _____________________

19. SGPT (IU/L) : _____________________

20. SGOT (IU/L) : _____________________

21. S. Alkaline phosphatase (KA unit) : _____________________

22. S. proteins (gm/dl) : _____________________


23. Blood Urea (mg/dl) : _____________________

24. S. Creatinine (mg/dl) : _____________________

Date: _____________ Signature of Investigator __________________________

103



(On Day 08)

FORM IV-B – LABORATORY INVESTIGATIONS


1. Centre: ………………..……….







Stool:

8. Ova (A. lumbricoids)/Cyst


104



(On Day 15)

FORM IV-C – LABORATORY INVESTIGATIONS


1. Centre: ………………..……….







Urine Examination

8. Routine: _________________________________

9. Microscopic: _________________________________

Stool examination

10. Routine: _________________________________

11. Microscopic: _________________________________

12. Occult Blood: _________________________________

13. Ova/Cyst (Ova of A.lumbricoids) : _________________________________

Blood

14. TC (Cells/Cmm.) _______________

105

15. DC - P _____ (%) L _____ (%) E ______ (%) M _____ (%) B ______(%)

16. ESR (mm / 1st hour.) __________

17. Hb (g/dl) ____________________


18. S. Bilirubin (mg/dl) : _________________________________

19. SGPT (IU/L) : _________________________________

20. SGOT (IU/L) : _________________________________

21. S. Alkaline phosphatase (KA unit) : _________________________________

22. S. proteins (gm/dl) : _________________________________


23. Blood urea (mg/dl) : _________________________________

24. S. Creatinine (mg/dl) : _________________________________


106



CASE REPORT FORM V-CONSOLIDATED DATA ON PERIODICALOBSERVATIONS


1. Centre: ………………..……….







Sl. Subjective/ objective 0 day/BT 8th day 15th day/ATNo Parameters Dt. Dt. Dt.

1. Jvara (Fever)

2. Vivarnata (Discoloration)

3. Shoola (Abdominal pain)

4. Hridroga (Cardiac disorders)

5. Sadana (Fatigue)

6. Bhrama (Giddiness)

7. Bhaktadwesha (Anorexia)

8. Atisara (Diarrhoea)

9. Swasakrichhrata (Dyspnea)

10. Hrillasa, Chhardi (Nausia,Vomiting)

11. Avipaka (Indigestion)

107

12. Anaha (Tympanitis)

13 Karshya (Cachexia)

14. Adverse reaction

Burning sensation in abdomen

Nausea

Diarrhoea

Skin rashes

Any other

15. TC (Cells/Cmm.)

16. DC P _____% P _____% P _____%L _____% L _____% L _____%E _____% E _____% E _____%M _____% M _____% M _____%B _____% B _____% B _____%

17. ESR (mm / 1st hour.)

18. Hb(g/dl)

19. Ova(A. lumbricoids) in thestool

20. Liver function tests

S. Bilirubin (mg/dl)

SGPT (IU/L)

SGOT (IU/L)

S. Alkaline phosphatase(KA unit)

S. Proteins (gm/dl)

21. Renal function tests

Blood urea (mg/dl)

S. Creatinine (mg/dl)

108

Overall clinical assessment


Overall impression of well being by the Subject:


Status of the Subject :

Continuing (1)

Drop out (2) Reason: ______________________________

Died (3) Cause: _______________________________


109

Drug: Study Code:


CLINICAL EVALUATION OF VIJAURA NIBU SWARASALONGWITH SAINDHAVA, KALAMI SHORA ANDNAUSADARA IN ONE GROUP VIS-A-VIS PATHAR

CHATTI SWARAS ALONGWITH IKSHUARAKA ANDKALI MIRCH IN THE MANAGEMENT OF

PITTASHMARI (GALL STONE)


110

Blank

111

I. BACKGROUND

Ayurvedic literature describes ‘Ashmari’ primarily as a disease of urinary tract. Vataj, Pittaj,Kaphaj and Shukraj these four types of Ashmaris are described in general. No specific etiology ortreatment has been mentioned Pittashmaris. However, the existence of ‘Pitteshu Iva Rochna go’ isconsidered Sushruta in Nidana Sthana Chapter III and Chikitsa Sthana Chapter VII describesAshmaris etiology and treatment respectively. The entire description belongs to the Ashmaris orurinary tracts. Gall stones are usually found in the gall bladder, but in 20 percent of cases, stonesmay be present in the bile duct. Most of the times, it is the one sone amongst which isresponsible for patient’s sufferings (Bailey & Love’s)1.

The factors responsible for the formation of gall stones may be:

- Metabolic

- Infective

- Bile Stone

The effects and complications of gall stones may be:

(i) Stone in gall bladder

- Silent stones

- Flatulent dyspepsia

- Gall stone colic

- Acute cholecystitis


CLINICAL EVALUATION OF VIJAURA NIBU SWARAS ALONG WITHSAINDHAVA, KALAMI SHORA AND NAUSADARA IN ONE GROUP VIS-A-VISPATHAR CHATTI SWARAS ALONG WITH IKSHUARAKA AND KALI MIRCH

IN THE MANAGEMENT OF PITTASHMARI (GALL STONE)

References

1. Harisson’s Principles of internal medicine, Volume-1, 14th Edition, International Editions, 1998,Published by McGraw-Hill Companies Inc .pp1208-1209


112

- Chronic cholecystitis

- Carcinoma

(ii) In the bile ducts

- Obstructive jaundice

- Acute/recurrent poncreatitis

- Cholangitis

(iii) In the intestine

- Acute intestinal obstruction

TYPE OF GALL STONES

The gall stones may be:

- Cholesterol

- Pigment stones (12% of gall stones)

- Mixed stones (majority 80-82% of gall stones)

A fat fertile, female of forty is an easy victim to the disease.

The incidence of gall-stone rises with diabetes mellitus, raised serum triglycerides,pregnancy, obesity, patients taking clofibrate, oestrogen replacement therapy and contraceptivepills. Patients with cirrhosis liver and hemolytic anemia have more chances of pigment stones.

Modern therapy advocates surgery/lithotripsy in most of the cases. Howeverchenodeoxycholic acid (10-15 mg./Kg./day) or Ursodeoxycholic acid 8-10 mg./Kg./day) may begiven to dissolve gall stone in 50-70% of the cases within 2 years. Recurrence can occur ondiscontinuation of the therapy.

The patient of cholelithiasis-cholecystitis may present as acute cholecystitis or chroniccholecystitis. The patients to be taken for Ayurvedic research may be of chronic cholecystitis.

II. OBJECTIVE

No significant contribution has been made to the treatment of Pittashmari (Gall Stone) inAyurvedic science, yet there are different claims. It has been considered worthwhile to find out theeffect of some claimed and popular Ayurvedic medicines, practiced to remove stone. The presentstudy is launched with a view to:

Study the disease incidence, Clinical picture and disease pattern of Pittashmari (GallStones).

113

See the effect of Vijaura Nimbu swaras + saindhava + Kalami Shora + Nausadara + Elacombination of radiologically/ultrasonographically proved cases of Pittashmari (Gall Stone).

See the effect of Pathar Chatti swaras + Ikshuraka Kshara + Kali Mirch in the diagnosedcases of Pittashmari (Gall Stone)

To study comparatively the effect of treatments in group (ii) and (iii).

III. CENTRE :

CCRAS identified Centres


No of Groups: 2

No of patients in each group: 20

(Patients to be randomly allocated to different treatment groups)

Treatment:

Group I: Vijaura Nibu swarasa — 750 ml.

Saindhava — 20 gm.

Kalami Shora — 10 gm.

Nausadara — 10 gm.

Ela — 10 gm.

Mixed and filtered — 20 ml. thrice a day for 30 days

Group II: Pathar Chatti swarasa — 10 ml

Ikshuraka Kshara — 1 gm.

Kali Mirch — 4 in number

(1 such thrice daily with water) for 30 days)

Type of Study: Single blind

Period of Study: 30 days

Follow up; For a period of 3 months on a regular interval of two weeks

114

V. CRITERIA OF INCLUSION

1) Age > 10 years < 60 years

2) Sex-either-sex

3) Chronicity: Disease note older more than 5-7 years.

4) Murphy’s sign: Pain/Catch in deep breath when the fingers are pressed below right coastalcartilage.

5) Patients of chronic cholecystitis/silent gall stones

6) Obese/non-obese

7) High lipid/normal lipid

8) Clinical feature of chronic cholecystitis with positive murphy’s sign.

9) Gall stone observed by definite investigative procedures e.g.

- Plain X-ray abdomen

- Oral cholecystogram

- Ultrasonography

- Endoscopic retrograde cholangiography and percutaneous hepatic cholangiography

VI. CRITERIA OF EXCLUSION

1. Acute cholecystitis

2. Acute pancreatitis

3. Carcinoma of gall bladder

4. Biliary enteric fistula

5. Diabetes mellitus

6. Pregnancy

7. Severe pain/fever/typhoid

8. Persistent

9. Jaundice

10. Empyema/septicaemia/shock

115

11. Patients on steroids

12. Patient with polyarteritis

VII. CRITERIA FOR WITHDRAWAL:

1. Discontinuation of treatment during the trial

2. Development of any complications

3. Aggravation of the disease symptoms

4. Any side effect of the drug


The full details of history and physical examination of the patients will be recorded as perthe proforma (Forms I & IA). Clinical and physiological assessment will be done before drugadministration and after every two weeks. The laboratory investigations- urine routine andmicroscopic, stool examination, blood sugar fasting & pp, lipid profile, x-rays: plain x-rayabdomen, oral cholecystogram, ultrasonography,endoscopic retrograde, cholangiography will berecorded before drug administration, at the end of treatment (Form-III)


Assessment will be done as per proforma after 3 months of regular treatment as per theproforma. However, the patients are to be reviewed after every two weeks.

1. Good Response: Complete disappearance of signs and symptoms with no complicationsand considerable regression in the size of the stone/complete disappearance of the stone.

2. Fair response: 50% and above relief in symptomatology with some regression in the sizeof the stone.

3. Poor response: 25% and above relief in symptomatology with no change in the size of thestone.




The progress of the trial will be monitored by CCRAS HQrs. New Delhi. Data analysiswill be undertaken at the Monitoring Unit CCRAS HQrs. New Delhi

116

XII. ETHICAL REVIEW

Each Institutional Ethical Committee (IEC) of participating centers should give clearancecertificate before the project is initiated. Patient’s information sheet and informed consent formshould be submitted along with project proposal for approval by IEC. Both should be maintainedin duplicate with one copy given to the patient at the time of entry to the trial.

117


CLINICAL EVALUATION OF VIJAURA NIBU SWARAS ALONGWITHSAINDHAVA, KALAMI SHORA AND NAUSADARA IN ONE GROUP VIS-A-VISPATHAR CHATTI SWARAS ALONGWITH IKSHUARAKA AND KALI MIRCH






Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included asa subject in the clinical trial on evaluation of vijaura nibu swaras alongwith saindhava,kalami shora and nausadara in one group vis-a-vis pathar chatti swaras alongwithikshuaraka and kali mirch in the management of pittashmari (gall stone).





Relationship ___________________________________


118






Research is going on to find a suitable natural product for the treatment of Pittashmari (Gllstone). You are invited to participate in such a study in which you will receive either Ayurvedictrial drugs or control drug for 30 days.

The aims of the present study are

• To see the effect of Vijaura Nimbu swaras + saindhava + Kalami Shora +Nausadara + Ela combination of radiologically/ultrasonographically proved cases ofPittashmari (Gall Stone).

• See the effect of Pathar Chatti swaras + Ikshuraka Kshara + Kali Mirch in thediagnosed cases of Pittashmari (Gall Stone)

• To study comparatively the effect of treatments in group (ii) and (iii

• Total 100 patients from this and other hospitals will be taking part in this study.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately six months to complete. After thisperiod, you are expected to visit the hospital every fortnight. The interval between the first andsecond visit will be around 15 days.

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination. ECG, Blood and urine samples will also be taken. This is to make sure thatyou are eligible for the study.

One week later, at your second visit, if you are eligible, you would be put on trial treatmentfor 30 days. You may receive either trial drug or control drug for 30 days. You should follow lifestyle modifications (Diets Advice, Exercise) as given along with information Sheet

From the first visit onwards, you will be required to fast overnight before attending each visit.Blood and urine samples will be taken at every visit. At each visit, you will be supplied withsufficient quantity of drug to last until your next visit.

119

What happens at the end of the study?

The trial treatment will be stopped at the end of 30 days. You will be put back on anappropriate treatment available in the market.

What are the alternatives?

Your doctor will be pleased to explain to you the available alternative treatment.

When you can leave the study?

Your participation in the study is entirely voluntary. You can choose to leave the study atany time. Your decision to leave the study will not affect your medical care or relationship withyour doctor.

Your doctor may decided that you should not continue in the study if, a) your blood sugarbecomes very high or very low, b) you start on insulin or other medication that affect blood sugar,c) you take part in any other trial.

What is the cost of the study?

All medication and tests to be done during the study will be free of charge.

If you do not want to participate, you are free to do so. It will not affect your medicalcare or relationship with your doctor in any way.

What happens now if you decided to take part?

You will asked to sign a consent form saying that you have been given information aboutthe study and you voluntarily agree to take part.

It is important to follow all instruction given by your doctor or doctor’s assistant carefully.




120



IN THE MANAGEMENT OF PITTASHMARI (GALL STONE).


BEFORE TREATMENT


1. Centre: ………………..……….





6. Address ……………………………………..………………………………………


1. Patient of chronic cholecystitis/Silent gall stone

2. Clinical features of chronic cholecystitis

3. Murphy’s sign positive

4. Chronicity < 5 – 7 years

5. Age > 10 yrs. < 60 yrs.

6. Sex – either sex

7. Obese/Non-obese

8. High lipid/Normal lipid

121


9. Acute cholecystitis

10. Acute pancreatitis

11. Carcinoma of gall bladder


13. Pregnancy

14. Colic/Typhoid/Jaundice

15. Biliary enteric fistula

16. Empyema/Septicaemia/Shock

17. Patient on steroids

18. Patients of polyarteritis


If Sl. No. 1-8 is ‘Yes’ and Sl. No. 9-18 are ‘No’

Date: ………………….. Signature of the Investigator: ………………………

122





1. Centre: ………………..……….


3. Name of the patient …………………………….....……… Age ………… Sex ………...

4. Address : ..............................................................................................................................

5. Date of Admission : Date of Discharge :

6. Group No. First (1) Second (2)

Third (3) Fourth (4)








9. Total income of the family (in Rupees)

Total family members:

Income per capita per month (in Rupees)

123

10. Religion Hindu (1) Muslim (2) Christian (3)

Parsi (4) Others (5)

11. Marital status Married (1) Unmarried (2) Divorcee/ (3)separated

CHIEF COMPLAINTS WITH DURATION (IN MONTHS)

Present (1) Absent (0) Duration

12. Pain abdomen

13. Dullache in Present hypochondrium

14. Distension (abdomen)

15. Fullness belching/retching

16. Nausea

17. Fever

18. Jaundice

HISTORY OF PRESENT ILLNESS

19. Onset of disease Acute(1) Insidious (2)

20. Duration of disease(in months)

21. Factors aggravating the disease/chief complaints: ……….………………………………...............……………………………………………………………………….……………

22. Factors relieving main complaints …………………………………………………………...........………………………………………………………………………………………

23. History of past illness, having relation with present illness

Yes (1) No (0)

If yes, specify…………………………………………………………….........……………

H/o Pancreatitis/Liver disease/Typhoid/Lipid disorders/Obesity

H/o Operation

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H/o Treatment-hepatotoxic drugs/oestrogens/steroids

FAMILY HISTORY IF ANY

Yes (1) No (0)

24. Carcinoma


26. Polyarteritis

27. Liver disease

28. Obese/Lipid disorders

If yes specify……………………………………......….…………………………………….

PERSONAL HISTORY

29. Diet Veg (1) Non-veg (2) Lacto-ova Veg (3)

30. Sleep Good(1) Disturbed (2) Insomnia (3)

31. Emotional Stress Yes (1) No (0)


If yes, specify………………………………………………………………………............

33. Sharirika Prakriti: Vataaj (1) Pittaj (2) Kaphaj (3)

Vataja-Kaphaj(4) Vataj-Pittaj (5) Pittaj-Kaphaj (6)

Sannipataj (7)

34. Manas Prakriti Sattava (1) Rajas (2) Tamas (3)

Sattava Rajas(4) Sattava Tamas(5) Rajas Tamas (6)

Sama (7)



125


37. Body weight (in Kg.)

38. Blood pressure (Systolic)

39. Blood pressure (Diastolic)

40. Pulse

41. Respiration rate

42. Anaemia Present (1) Absent (0)

43. Jaundice Present (1) Absent (0)

44. DIGESTIVE SYSTEM

P/A – Soft Yes (1) No (0)

Non-tender

Liver Yes (1) No (0)

Palpable

Tender

Gall Bladder Yes (1) No (0)

Palpable

Tender

Spleen Yes (1) No (0)

Palpable

SYSTEMIC EXAMINATION Normal (1) Abnormal (2)

45. C.V.S. (With Chest)

If abnormal, specify abnormalities……………………………………….............…………..

46. C.N.S

If abnormal, specify abnormalities………………………………………………...............

126


If abnormal, specify abnormalities…………………………………………………..

48. Uro-Genital system




SAMPRAPTI (PATHOLOGENESIS) OF THE DISEASE ACCORDING AYURVEDICCONCEPT

50. Dosa Vata (1) Pitta (2) Kapha (3)

51. Dushya (Involved) Rasa (1) Rakta (2) Mamsa (3)


Shukra (7) Ojas (8)

52. State of disease (Roga Kriya Kala)

Sanchaya(1) Prakopa(2) Prasar (3)

Sthansamshraya (4) Vyakti (5) Bheda (6)

RAKTA VAHA SROTAS Yes (1) No (0)

Pidika

Rakta Pitta (Bleeding)

Mukhapak

Vidradhi (Abcess)

Kamla

PURISHA VAHA SROTAS Yes (1) No (0)

Atibadha Purisha

Atidhrava Purisha

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Scantly stool

Excessive faecal matter

Painful defecation

Increased frequency of defecation

LAB INVESTIGATION

Microscopic

1. Urine

Routine

2. Blood

(i) Hb%

(ii) TLC

(iii) DLC

(iv) ESR

BIOCHEMICAL

Microscopic

(1). Urine

Routine

(ii) Lipid profile

(iii) HDL

(iv) LDL

(v) VLDL

(vi) S. CHOLESTEROL

(vii) Serum Triglycerides

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X-RAY

(i) Plain X-ray abdomen

(ii) Oral cholecystogram

(iii) Ultrasonography

(iv) Endoscopic retrograde cholangiography

Provisional Diagnosis

Final Diagnosis

Medical Management

Principal Drug Therapy

Dose

Vehicle

Diet

Summary of findings

Results Good Response (1) Fair Response (2)

Poor Response (2) No Response (4)

Drop out (5) LAMA (6)

Date: ……………… Signature of the Investigator: ………………………...

129




CASE REPORT FORM III– CLINICAL ASSESSMENT

1. Centre: ………………..……….


3. Name of the patient …………………………….....……… Age ………… Sex ………...

4. Address : ..............................................................................................................................

5. Date of Admission : Date of Discharge :


Third (3) Fourth (4)

CLINICAL PARAMETERS

(A). SUBJECTIVE YES (1) NO (0)

Pain abdomen

Fullness/belching/wretching

Nausea/Vomiting

Fever

Dullache in right hypochondrium

Abdominal distention/epigastric discomfort

(B). OBJECTIVE YES (1) NO (0)

Jaundice

Hyprochondriac tenderness

Date: _____________ Signature of the Investigator: _______________

130




CASE REPORT FORM IV – LABORATORY INVESTIGATION

1. Blood Sugar: Fasting

Post Prandial

2. E.S.R.

3. Lipid Profile

- HDL

- LDL

- VLDL

- S. Cholesterol

- Serum Triglycerides

4. X-RAYS Before treatment After treatment

- Plain X-ray abdomen

- Ultrasonography

- Oral Cholecystogram

Date: ______________ Signature of the Investigator: ______________________

131

Drug: Study Code:


CLINICAL STUDY ON SERO CONVERSION OF HBsAg (CARRIERS) WITH CODED AYURVEDIC

FORMULATION ‘AYUSH-LIV’


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I. BACKGROUND

Hepatitis B1 is one of the major diseases of mankind and is a serious global public healthproblem. It is preventable with safe and effective vaccines that have been available since 1982.Hepatitis B Virus (HBV) is the most versatile of the hepatotropic Viruses. HBV can produce (1)Acute hepatitis (2) Chronic non progressive hepatitis (3) Progressive chronic disease ending incirrhosis (4) Fulminant hepatitis with massive liver necrosis and (5) an a symptomatic carrier withor without progressive disease. It has been documented by the WHO that world wide, there areover 400 million hepatitis ‘B’ carriers, of which 42 million are in India alone. These carriers are at200 times greater risk of developing serious liver complication including cirrhosis and liver cancer.

An HBV carrier is one who had hepatitis B in his blood for more than six months. Acarrier usually has no signs or symptoms of HBV but remains infected with the virus for years orfor a life time and is capable of passing the disease on to others. Sometimes HBV carriers willspontaneously clear the infection from their bodies, but most will not. Any one who has not clearedthe virus after six months and has elevated liver enzymes is considered to have chronic hepatitis.This means, the virus is infecting living liver cells and damaging them. Scar tissue called cirrhosisreplaces the damaged cells. The build up of Cirrhosis causes the liver to become hard and bumpyand distorts the blood flow through this vital organ.

Characteristics of a HBs Ag Carrier state:

Carriers usually have no history of acute hepatitis and no clinical features of liver disease.All of them have HBs Ag in blood. Some have HBe Ag and Anti HBe. Most of them havenormal liver function tests. Prognosis is uncertain. Virus can be carried for years. Some developchronic hepatitis and others are at increased risk of developing cirrhosis and hepato cellularcarcinoma.

Transmit ion of infection:

Hepatitis B Virus is transmitted by contact with blood or body fluids of an infected personin the same way as human immuno-deficiency Virus (HIV). However HBV is 50 to 100 timesmore infectious than HIV.


CLINICAL STUDY ON SERO CONVERSION OF HBs Ag (CARRIERS) WITHCODED AYURVEDIC FORMULATION ‘AYUSH-LIV’

References

1. Harrison’s Principle of Internal Medicine 15th Edition

134

The Hepatitis B Virus (HBV) gets transmitted through

1. Prenatal (From mother to baby at the birth)

2. Child to child transmission

3. Unsafe injections and transfusions

4. Sexual contact

Hepatitis B virus is not spread by contaminated food or water and cannot be spreadcasually in the work place.

Viral markers:

Chronic HBV infection is marked by the presence of HBs Ag) in the blood. At times theHbe Ag and Anti Hbe is also present. Presence of Hbe Ag indicates active viral replication.Presence of Anti Hbe implies that replication is occurring at much lower level or that viral DNAhas become integrated into host Hepatocyte DNA.

PCR: Polymerase chain reaction can show HBV DNA in the blood, implying that viralreplication is occurring. This is essentially needed for formulating the treatment protocol..

As per Ayurvedic texts several plant drugs are known for its hepato protective, antihepatotoxic and anti-viral properties. A coded drug Ayush-Liv with four herbal ingredients havingabove mentioned properties is selected to explore the possibilities of these drugs in combination inthe clearance of Hepatitis-B Virus.

II. OBJECTIVES

1. To study the efficacy of the Ayush-Liv formulation to get the viral marker, Hbs Ag seronegative.

2. To study the efficacy of Ayush-Liv formulation in maintaining the liver parameters withinnormal limits.

III. CENTERS



Sample size: 30 cases

Type of Study: Open trial

Trial Drug /Dosage /Duration

Group I - Allopathic drug + placebo (60 days)

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Group II - Allopathic drug + AYUSH-LIV (two Caps, 550mg each twicea day after food with water).

Type of study: Placebo controlled study

Period of study: Two months for each case and Post study surveillance screeningfor one month. Total duration will be two years to complete thestudy.

Follow Up : One follow up will be carried out after three months of completionof the treatment.


1. Age between 18-60

2. HBs Ag positive in blood (Eliza test) for past 6 months.

3. ALT/SGPT > 1.5 ULN (Upper Limit Normal)

4. HBV DNA > 105 Viral copies/ml.

5. Compensated liver disease.


1. Age below 18 and above 60 years.

2. Past history of Jaundice

3. Negative for HBsAg

4. ALT/SGPT > 10 x ULN

5. Positive for IgM anti HBc

6. History of decompensated liver disease

7. Co-infection with HDV, HCV (or) HIV

8. History of Drug / Alcohol addiction

9. Any other serious systemic ailments


i) If any substantial increase in LFT parameters is observed in subsequent investigations thecase will be withdrawn.

ii) A case will be withdrawn from the study if there is development of any major ailments orclinical symptoms of Jaundice.

136

iii) Patients failure to report for follow up or irregular medication (discontinuation for sevendays or above)

Patients withdrawn from the study will be managed by the Investigators.

VIII. ROUTINE EXMINATION AND ASSESSMENT

The full details of history and physical examination of patients will be recorded as per theProforma (Form I &IA). Clinical assessment will be done before drug administration, everyfortnightly till the completion of the treatment. The laboratory investigations will be recorded beforedrug administration, every month till the end of treatment and at the end of follow-up. [Form III].

Anti HCV, Anti HDV, IgM,Anti HBc, anti HBs, Anti HIV : At the time of inclusion

HBeAg and anti HBe, HBsAg, : Before treatment and every month till the end ofAnti HBs and LFT treatment and at the end of follow-up.


i) If HBs Ag becomes sero negative during treatment or after completion of the treatment itwill be considered a successful outcome of the treatment.

ii) Normalization of ALT levels and maintaining within normal levels.

X. STATISTICAL ANALYSIS


XI. TRIAL MONITORING AND DATA ANALYSIS


XII. ETHICAL REVIEW


B. Data and safety monitoring board: A Data and safety monitoring board(DSMB) at Hqrs. will carefully monitor the data and side effects during the period of study andput in a place where by prompt reporting of adverse events occur. The data will be reviewed as

137

every 20 participants entered the study and administered the trial drugs. The research team willreport immediately to the PI and Data Monitoring Board if, any life threatening conditions whetherthey are perceived to be study related or not. The Board decides whether the adverse effectswarrant discontinuation of the study protocol. Protocols will be written and approved for thetreatment of study related adverse events.


A consolidated amount of Rs.……. /- per visit will be paid to subject.





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CLINICAL STUDY ON SERO CONVERSION OF HBs Ag (CARRIERS) WITHCODED AYURVEDIC FORMULATION ‘AYUSH-LIV’





Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on healthy carriers of hepatitis ‘B’ with herbal compounds.





Relationship ___________________________________


139


PROTOCOL FOR CLINICAL STUDY ON SERO CONVERSION OF HBs Ag(CARRIERS) WITH CODED AYURVEDIC FORMULATION AYUSH-LIV



Hepatitis ‘B’ virus (HBV) is the most Versatile of the hepato tropic viruses. It canproduce acute or chronic; progressive or non progressive hepatitis and exists in a carrier statepermanently with or without progressive disease. It has been documented by the WHO thatworld wide there are over 400 million hepatitis ‘B’ carriers of which 42 million are in India alone.These carriers are 200 times greater risk of developing serious liver complication including cirrhosisand liver cancer. As per Ayurvedic literature several plant drugs are known for its hepatoprotective, anti hepato toxic and antiviral properties. So a few drugs such as Katuki (Piccrorhizakurroa), the present study is aimed to evaluate role of selected Ayurvedic drugs in clearance ofVirus B infection in healthy carriers. You are invited to participate in this study where you will beprovided this drug. The previous observations in clinical and experimental studies have shownpromising effect of these drugs in the treatment of Viral Hepatitis. About 100 healthy carriers fromthis hospitals and cases referred from other hospitals will be taking part in this study.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately three months to complete (two monthsfor treatment and another one month for follow-up study). During this period, you are expected tovisit the hospital three times. The interval between the first, second and third visit will be onemonth.

Before you start treatment, during the first visit to the OPD, you will undergo a completephysical examination, Blood and urine samples will also be taken and also tested for all the viralmarkers for Hepatitis ‘B’. This is to make sure that you are eligible for the study.

If you are found eligible, you would be put on trial treatment for two months. The dailydosage will be two Caps of 550mg each twice daily. At each visit, you will be supplied withsufficient quantities of drugs to last until your next visit.


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BEFORE TREATMENT


1. Centre: ………………..……….





6. Address ……………………………………..………………………………………

CRITERIA FOR SELECTION Yes (1) No (0)

1. Age between 18-60

2. HBs Ag positive in blood (Eliza test) for past 6 months.

3. ALT/SGPT > 1.5 ULN (Upper Limit Normal)

4. HBV DNA > 105 Viral copies/ml.

5. Compensated liver disease.



7. Past history of Jaundice

8. Negative for HBsAg

9. ALT/SGPT > 10 x ULN

10. Positive for IgM anti HBc

141

11. History of decompensated liver disease

12. Co-infection with HDV, HCV (or) HIV

13. History of Drug / Alcohol addiction

14. Any other serious systemic ailments


If Sl.No. 1 - 5 is ‘YES’ and Sl.No. 6 - 14 are ‘No’

If admitted: Subject’s Serial No. __________ No. of packets issued: ___________

Date: ____________ Signature of the Investigator: ______________________

142





1. Centre: ………………..……….






7. Address ……………………………………..……………..........…………………………





Housewife (3) Others (4)


10. Income

Total Members in the family : ___________________________________________

Total Income in the family : ___________________________________________

Per capita income : ___________________________________________

143

History of Past Illness Yes (1) No (0)

11. Jaundice

12. Major or minor surgery With blood transfusion

If yes, indicate amount of blood transfusion _____________________

13. I.V. Fluids

Any injection

14. Intramuscular

If yes, indicate number of injections taken_______________________

15. Intravenous

If yes, indicate number of injections taken_______________________

16. Any history of drug abuse

If yes, provide details about drugs and mode of consumption _______

17. Previous treatment for Jaundice

If yes, provide details regarding time and period of illness__________

Personal History

18. Marital status Married (1) Unmarried (2) Widow (3)

Widower (4) Divorced (5)

19. Sexual orientation Heterosexual (1) Homosexual (2)

Bi-sexual (3) Others (4)

Addiction

20. Alcohol No (0) Yes (1)

If yes specify (a) Quantity per week (ml) ______________


144

21. Any other, specify: ___________________________________________________


22. Height (cm) ____________

23. Weight (kg) ____________

24. Pulse (per min) ____________

25. Blood Pressure Systolic(mm Hg)____________

26. Blood Pressure Diastolic (mm Hg) ____________

27. Respiration rate( per min) ____________

Systemic examination Normal (1) Abnormal (2)

28. CVS

If abnormal details___________________________________________


If abnormal, details ___________________________________________

30. CNS






Clinical Symptoms Absent (0) Present (1)

33. If any

If Present, specify____________________________________________

No. of packets issued: _______________________________________

Date:____________ Signature of the Investigator: ______________________

145


PROTOCOL FOR CLINICAL STUDY ON HEALTHY CARRIERS OFHEPATITIS ‘B’ WITH CODED AYURVEDIC FORMULATION AYUSH-LIV

(0th, 1st & 2nd Month)

CASE REPORT FORM III – CLINICAL ASSESSMENT

1. Centre: ………………..……….






7. Date of Assessment:

8. Period of Assessment: Initial (0) 1st Month (1) 2nd Month (2)

CLINICAL ASSESSMENT Yes (1) No (0)

9. Fever

10. Anorexia

11. Nausea

12. Vomiting

13. Yellow tint of the sclera

14. Dark coloured urine

15. Clay coloured stools

16. Malaise

Date: __________ Signature of the Investigator__________________

146


PROTOCOL FOR CLINICAL STUDY ON SERO CONVERSION OF HBs Ag(CARRIERS) WITH CODECD AYURVEDIC FORMULATION AYUSH-LIV

(0, First & Second Month)

CASE REPORT FORM IV– LABORATORY INVESTIGATIONS

1. Centre: ………………..……….







8. Period of Assessment: Initial (0) 1stMonth (1) 2ndMonth (2)

Urine Examination (Microscopic)

9. Sugar: ___________________

10. Albumin: ___________________

11. Deposits: ___________________

Blood

12. TLC (Cells/Cmm.)_____________________

13. DLC: P (%)________ L (%)________ E (%)________M (%)________ B (%)________

14. Hb(g/dl): ________________

15. ESR (1st hour.)(m.m.): ________________

16. Blood Sugar-Fasting (mg/dl): ________________

147

17. Blood Sugar – PP (mg. /dl): ________________

18. S.Cholesterol (mg./dl): ________________

19. HDL (mg. /dl): ________________

20. LDL (mg. /dl): ________________

21. Triglycerides (mg. /dl): ________________

22. B. Urea (mg. /dl): _______________

23. S.creatinine (mg. /dl): _______________

24. SGOT (IU/L) : _______________

25. SGPT (IU/L) : _______________

26. Serum bilirubin total (mg/dl) : _______________

27. Serum bilirubin direct (mg/dl) _______________

28. Serum bilirubin indirect (mg/dl) _______________

29. Alk.Phosphatase (IU/L) _______________

30. Total protein (gms/dl) _______________

31. Albumin (gms/dl) _______________

32. Globulin (gm/dl) _______________

Serology Routine (to be done at 0, 1st & 2nd month)

33. HBsAg _______________

34. HBeAg _______________

35. Anti HBe _______________

36. Anti HBs _______________

37. HBV DNA (viral load) _______________

Serology (to be done at 0 month)

38. IgM anti HBc _______________

39. Anti HCV _______________

148

40. Anti HDV _______________

41. Anti HIV 1 & 2 _______________

Physiological Parameters

42. Systolic Blood Pressure (mm of Hg) _______________

43. Diastolic Blood Pressure (mm of Hg) _______________

44. Weight (Kg) _______________

45. Any other Remarks

Date: ____________ Signature of the Investigator: ____________________

JOINT DISORDERS

SEC

TIO

N - III

150

Blank

151

Drug: Study Code:


COMPARATIVE CLINICAL EVALUATION OFPHANCHKARMA VERSUS PHYSIOTHERAPY IN

PATIENTS OF SANDHIVATA (OSTEOARTHRITIS) -KNEE JOINT


152

Blank

153

I. BACKGROUND

Panchakarma is a textual classical and authentic treatment procedure of Ayurveda. Ourancient sages and scholars like Charaka and Vagbhatta have attributed a lot of potential benefitsto Panchkarma practices. The aim of the study is to see the effect of Panchakarma in group Ipatients of Sandhivata (Osteoarthritis) and to compare the results with known physiotherapytreatment in the patients of group II. This Physiotherapy treatment is usually referred to by doctorsof various Systems of Medicines1.

II. OBJECTIVE

Comparative clinical evaluation of Panchkarma versus Physiotherapy in patients ofSandhivata (Osteoarthritis) - knee joint, with selected clinical parameters.

III. CENTRES

CCRAS identified centers


Type of study : Open trial

Level of study : OPD/IPD

Number of Groups : Two Groups

Sample Size : 30 (15 patients in each group)

COMPARATIVE CLINICAL EVALUATION OF PHANCHKARMA VERSUSPHYSIOTHERAPY IN PATIENTS OF SANDHIVATA (OSTEOARTHRITIS)-

KNEE JOINT

References

1. Charaka Samhita with Ayurveda Dipika commentary of Chakrapanidatta, Chikitsa Sthana, Chapter – 28,Chaukhambha Sanskrit Sansthan, 5th edition, Varanasi, 2001

2. Clare Jinks, Kelvin Jordan Measuring the population impact of knee pain and disability with theWestern Ontario and McMaster Universities Osteoarthritis Index. Pain 2002: 100, 55-64.

3. Gail D Dyele, Stephen C Allison, Robert L Matekel. Physical Therapy treatment effectiveness forosteoarthritis of the knee: A randomized comparison of supervised clinical exercise and manual therapyprocedures versus a home exercise program. Physical Therapy 2005: 85, 12, 1301-1317.

4. Effects of repetitive shortwave diathermy for reducing synovitis in patients with knee osteoarthritis: Anultrasonographic study Physical therapy 2006: 86, 2, 236-244.

154

Drug/Dosage/Duration:

Group-I Panchkarma Group:

• Local application of Pancaguna Taila 10-15 ml each joint, thrice a day

• Nadi Sweda with Dashmoola Kwatha for 15 minutes, followed by rest for 15minutes.

The above mentioned Panchkarma treatment will be given for 4 weeks in the hospitalfollowed by 2 weeks Pancaguna Taila application at home.

Group-II Physiotherapy Group:

• Exercise Protocol for 4 weeks continuously in the hospital which will consist ofManual Therapy, Stretching, Strengthening, and Range of Motion Exercises, followedby exercises at home for another 2 weeks.

• Associated with above treatment, shortwave diathermy (a type of thermal therapy) forinitial 2 weeks (6 days/ week).

Duration of treatment : 4 weeks in both the groups

Follow up period : After 2 wks



2. Sex-Either sex

3. Patients with Primary Osteoarthritis – knee joints (single or both knees)

4. Kellgren Lawrence (Radiological scale) of e” 2.

Note: Patients taking Ayurvedic/Allopathic NSAIDs orally may be included in the study but thetreatment may be considered as basal treatment and it should not be altered during the trial.


1. Age less than 40 years or more than 70 years.

2. Patients with skin allergies/skin diseases

3. Patients with Pott’s spine/infections/other systemic diseases

4. Patients with systemic conditions such as Gouty Arthritis, Rheumatoid Arthritis PsoriaticArthritis, SLE.

5. Patients with Diabetes/Hypertension

155

6. Bed ridden patients

7. Patients using local Anti-inflammatory medicine other than the research drugs.

8. Patients taking active Allopathic/Homeopathic treatment.

9. Low backache with or without radiation to legs.

10. Patients with metallic implants.

11. Subjects having any deformity of knee, hip or back.

12. History of bony or soft tissue injury to knee joint.


During the course of treatment, if any serious condition or any serious adverse eventsoccurs or pain/stiffness/swelling increases, or if subject himself/herself wants to withdraw from thestudy, such subjects may be withdrawn from the study.

VIII. ROUTINE EXAMINATION/ASSESSMENT:-

Inclusion into study - 0 day

1st assessment - 14th day

2nd assessment - 28th day

3rd assessment - 42nd day

Assessment Chart – annexed in case record form.

(Based on visual analogue scale).

Radiography-I

To diagnose the patients (at or before day 0) at the time of inclusion.

Radiography-II

To be compared with Radiography-I at the time of final assessment i.e. 45th day.

However much radiographical changes are not expected.

Result expectations:

30 to 35% improvement is expected in treatment groups.

However 10 to 20% improvement may also be there in placebo group.


Clinical symptoms and laboratory parameters will be analyzed using appropriate statisticalmethods.

156

X. TRIAL MONITORING

Monitoring unit of CCRAS Headquarters, New Delhi will monitor the progress of the trial.Data analysis will be undertaken by the Monitoring unit at CCRAS headquarter.

XI. ETHICAL REVIEW

A. Institutional Ethical Committee (IEC): The proposal will be placed before EthicalCommittee (IEC) of trial center for getting clearance certificate before the project is initiated.Patient’s information sheet and informed consent form will be submitted along with projectproposal for approval by EC. Both will be maintained in duplicate with one copy given to thepatient at the time of entry to the trial.

B. Data and Safety Monitoring Board (DSMB): A Data and safety monitoring board(DSMB) at Hqrs. will carefully monitor the data and side effects during the period of study andput in a place where by prompt reporting of adverse events occur. The data will be reviewed asevery 20 participants entered the study and administered the trial drugs. The research team willreport immediately to the PI and Data Monitoring Board if, any life threatening conditions whetherthey are perceived to be study related or not. The Board decides whether the adverse effectswarrant discontinuation of the study protocol. Protocols will be written and approved for thetreatment of study related adverse events.

XII. TRAVELING EXPENSES FOR RESEARCH SUBJECTS

A consolidated amount of Rs……. /- per visit.

XIII. TRAINING TO INVESTIGATORS AND PERSONS INVOLVED

Short-term two-day training will be provided to the Investigators and Laboratorypersonnel involved in the multi-centric trial at CCRAS Hqrs. The investigators and technicians willbe detailed about the clinical trial conduct and laboratory procedures in order to maintain theuniformity.

XIV. LABORATORY INVESTIGATIONS


Counseling about life style:-

During the research period, the patient should maintain uniform life style or basal life style(what he was adopting in general). Over exercise, over strain, riding bicycle, going upstairs orsitting in squatting positions may seriously alter the results.

157

To Check the drug compliance

The packing of the oil should be proper with no mark over the bottle so as to avoid bias.At each visit, patient must bring his/her medicine bottle and submit it to the researcher so that theconsumption of medicine may be checked.

Expected medicine requirement for 42 days

Oil requirement for 6 weeks (42 days):

One application on one joint = 10-15 ml x 3 times a day

= 30-45 ml.

In case of two joint involved 60 - 90ml per day.

Let us take average of 50ml per day per patient.

Thus total oil requirement for 42 days for 15 patients will be = 50 x 42 x 15

= 32 liters

Medicine requirement for 4 weeks (28 days):

Dashmoola required per day per patient = 50 gms

Requirement for 28 days for 1 patient = 50 x 28

= 1400 gms

Thus total medicine required for 28 days for 15 patients = 50 x 28 x 15

= 21kg

PHYSIOTHERAPY TREATMENT

1. Patient Exercise Program: Strengthening Exercises

Exercise Performance Repetitions

Static quadsets in kneeextension

Perform dailyPatient is positioned fully supine orsupine supported on elbows with theknee in full extension. Patient contractsthe quadriceps femoris muscle andpushes the knee down while maintainingthe foot in full dorsiflexion.

Hold each contraction for 6 swith a10-s rest between repetitionsRepeat 10X

158

Standingterminal kneeextension

Closed-chainprogression,ordered fromleast tomostchallen-ging

1. Seatedlegpresses

2. Partialsquats weightlessenedwitharm supportas needed

3. Step-ups

Perform 3 X per weekPatient stands with a resistive band or acuff from a weighted pulley mechanismbehind a slightly flexed knee. Patientcontracts the gluteal and quadricepsfemoris muscles to fully straighten the hipand knee

Patient performs one of the followingactivities 3X per week.Patient should progress to the mostchallenging activity that he or she cansuccessfully complete with minimal or nopain

Patient is seated holding a resistive bandin both hands. Patient places his or herfoot against the band, then straightensthe knee by pushing the foot down andforward by contracting the gluteal andquadriceps femoris muscles

Patient stands with arm support asneededPatient performs a partial squat, keepingthe knees centered over the feet. Returnto standing by contracting the quadricepsfemoris and gluteal muscles

Patient stands in front of a low step.Patient places foot of involved leg onstep and brings body over foot to standon the step. Use as little push-offassistance from the contralateral foot aspossible. Step down with thecontralateral foot

Hold each contraction for 3 s.Repeat 10XIncrease resistance astolerated

Hold each contraction 3 swith knee as straight aspossible. Slowly return tostarting position and repeat fora 30 s bout.Progress to bands ofincreasing resistance andadditional bouts

Hold each contraction 3 swith hips and knees asstraight as possible. Repeat for30 s Progress to full bodyweight withoutsupport and additional bouts

Slowly repeat for 30 sProgress to increased height ofthe step and additional bouts.Alternate legs if both kneesare involved

159


Standing calfstretch

Supinehamstringmuscle stretch

Pronequadricepsfemorismuscle stretch

Perform dailyPatient stands with the heel of the footon the ground behind the patient; thetoes point straight ahead. The patientleans forward until a moderate pull isperceived in the calf musculature. Thepatient may use his or her arms forsupport against a wall or furniture asneeded

Perform dailyPatient is positioned supine with thecontralateral lower extremity maintainedas straight as possible. The ipsilateral hipis flexed to 90°The knee is straightened and theproximal lower leg supported with thehands until a moderate pull is perceivedin the posterior thigh and calf Theipsilateral ankle should be dorsiflexed

Perform dailyPatient is positioned prone with bothhips and knees. A strap is placed aroundthe ipsilateral ankle and broughtposteriorly and superiorly over theipsilateral shoulder. The patient graspsthe strap in the ipsilateral hand andbends the knee by straightening his orher elbow and pulling on the strap. Theknee is progressively flexed until a gentlestretch is perceived in the anterior thigh

Hold for 30 s and repeat 3X

Hold for 30 s and repeat 3XClinical observation: ifradicular symptoms areproduced, decrease oreliminate the ankle dorsiflexionor the intensity of the stretch

Hold for 30 s and repeat3XClinical observation:hamstring muscle crampingmay occur if the patientattempts to actively bend theknee; to reduce this possibility,always use the strap topassively flex the kneeMaintain a gentle stretch andcomfortable position for thelumbar spine. Hard stretchingwill frequently create lumbarsymptoms in this population

2. Patient Exercise Program: Stretching Exercises

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3. Patient Exercise Program: Range of Motion Exercises


Knee in mid-flexion to full-extension

Knee in mid-flexion to full-flexion

Stationerybicycle

Perform dailyPerformed once dailyPatient is positioned supine or supinesupported on elbows Knee is broughtto 45° of flexion with the ipsilateral footsliding on the surface that the patient islying on. The knee is then fully extendedwith a strong quadriceps femoris musclecontraction against any limitation to fullknee extension.

Performed once dailyPatient is positioned supine or supinesupportedon elbows Knee is brought to full flexionwith assistance of the upper extremitiesor a strap A gentle challenge to end-range flexion is sustained.

Performed once dailyKnees should be at nearly full extensionat bottom of pedal stroke

Two 30-s bouts with 3-s holdat end rangeClinical observation: theseexercises work best ifperformed on a smoothsurface such as a hardwoodor linoleum floor or if a slidingboard is used

Two 30-s bouts with 3-s holdat end range.Clinical observation: pain withend-range knee flexion maybe due to degenerativemeniscal tearsOver-pressure to end rangeshould be applied withcaution.

5 min, increase time astoleratedClinical observation: somepatients are intolerant of thestationary bicycle, and clinicaljudgment is required tocontinue the activity.

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4. Common Knee Impairments Addressed by Manual Therapy

Impairment Manual Intervention Typical Delivery

Loss of kneeextension

Loss of kneeflexion

Loss ofpatellar glides

Muscletightness

Manual mobilization through range ofmotion (ROM) and knee extension atend rangeKnee extensionKnee extension with valgus or abductionKnee extension with varus or adduction

Manual mobilization through ROM andknee flexion at end rangeKnee flexionKnee flexion plus medial (internal)rotation

Manual mobilization of the patella in 5°–10° of knee flexionMedialLateralCaudalCephalad

Manual stretches at end length of themuscleQuadriceps femoris

Mobilization grades III andIV to III++ and IV++ 2–6bouts of 30 s per manualtechniqueClinical observation: thismanual intervention mayprovide near-immediatedecrease of symptoms andmay be approached withrelatively more vigor thanknee flexion

Mobilization grades of III-and IV- to III+ and IV+ 2–6bouts of 30 s per manualtechniqueClinical observation: pain withend-range knee flexion maybe due to degenerativemeniscal tears; end-rangetechniques should beutilizedwith caution.

Mobilization grades of IV toIV++ 2–6 bouts of 30 s permanual technique.Clinical observation: somepatients may be intolerant ofeven slight compressive forcesover the patella; therapisthand placement is Important.

Sustained manual stretches of12–30 s duration repeated 1–3 times per muscle.

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Soft tissuetightness

HamstringsGastrocnemiusAdductorsIliopsoasTensor fasciae latae and the iliotibialband

Soft tissue mobilizationSuprapatellar and peripatellar regionsMedial and lateral joint capsulePopliteal fossa.

Clinical observation: thelumbar spine should bemanually stabilized andprotected during all extremitystretches, particularly hipflexor stretches; many ofthese patients also will havearthritic changes in the spine,and symptoms can beincreased without care inpositioning.

Circular fingertip and palmpressure mobilization at thedepth of the capsule orretinaculum for 1–3 bouts of30 s per area.Clinical observation: the softtissue work in the poplitealfossa seems to work bestwhen performed slowly withoccasional sustained positionsof 10–12 s, this techniqueworks well when combinedwith the manual mobilizationsinto knee extension.

5. Method of Delivery of Short Wave Diathermy

Position of patient: supine lying with a pillow below the knee joint.

Method used: capacitive method using pad electrodes.

Electrode placement: Contra planar across the medial-lateral aspect of the knee.

Intensity: the intensity should be adjusted to produce a sensation of mild warmth in thepatient. Patient is made to appreciate the warmth by asking him/ her to blow at the hand.The degree of warmth felt at the knee should be same as that felt at the hand.

Duration: 20 minutes.

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KNEE JOINT

INFORMED CONSENT FORM




Name: ____________________________

CONSENT BY SUBJECT

The attending physician, the purpose of the clinical trial and the nature of drug treatmentand follow-up have informed me to my satisfaction, including the laboratory investigations to beperformed to monitor and safeguard my body functions.


I, exercising my free power of choice, hereby give my consent to be included as a subjectin the “Comparative clinical evaluation of phanchkarma versus physiotherapy in patients ofsandhivata (osteoarthritis)-knee joint”.





Relationship ___________________________________


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KNEE JOINT



Panchakarma is a textual classical and authentic treatment procedure of Ayurveda. Ourancient sages and scholars like Charaka and Vagbhatta have attributed a lot of potential benefitsto Panchkarma practices. The aim of the study is to see the effect of Panchakarma in groupIpatients of Sandhivata (Osteoarthritis) and to compare the results with known physiotherapytreatment in the patients of group II. This Physiotherapy treatment is usually referred to by doctorsof various Systems of Medicines.

Expected duration of the subject participation

An Ayurvedic physician along with a physiotherapist will take a brief history of the subjectand reveal him/her the facts about the benefits and side effects of the procedure. The volunteerwill be subjected to:

Local application of Pancaguna Taila 10-15 ml each joint, thrice a day, Nadi Sweda withDashmoola Kwatha for 15 minutes followed by rest for 15 minutes in group I.

The above mentioned Panchkarma treatment will be given for 4 weeks in the hospitaland then followed by 2 weeks Pancaguna Taila application at home.

In group II, Exercise Protocol for 4 weeks continuously in the hospital (consisting ofManual Therapy, Stretching, Strengthening, and Range of Motion Exercises), followed byexercises at home for another 2 weeks.

With above treatment, shortwave diathermy (a type of heat- therapy) for initial 2 weeks (6days/ week) will be associated.

The benefits that might be expected from the out come of the research to the subject

The patients suffering from Sandhivata / OA, selected from CRIA will serve the cause ofscience by participating in the study. We may be able to re-establish the facts and science ofAyurveda already in use by our ancestors for last 2000 years. This treatment is expected to reducepain and swelling of the affected joints. The additional benefits that the subject may get that his/herrelated investigations will be done free of cost .Apart from this the functional status of the patientwill improve.

165

Any risk to the subject associated with the study

Though the side effects are not very common, however in rare cases patient might developallergy with the oil. At times local irritation/ skin burn may happen during heat application.

Maintenance of the confidentiality of records

The records of the study will be kept confidential to protect volunteer’s privacy.

Compensation of subjects for disability or death resulting from injury

Not applicable

Freedom of individual to participate and to withdraw from research at anytimewithout penalty or loss of benefits to which the subject would otherwise be entitled

Subjects will be free to withdraw from the study at any stage without assigning any reason,without penalty or loss of benefits to which he/she would otherwise be entitled.


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CASE REPORT FORM – 1 SCREENING

Before Treatment

(Please tick � wherever is applicable)

1. Centre: ………………..……….





6. Address ……………………………………..………………………………………




2. Sex-Either sex

3. Patients with Primary Osteoarthritis – knee joints(single or both knees)

4. Kellgren Lawrence (Radiological scale) of ≥ 2.


8. Age less than 40 years or more than 70 years.

9. Patients with skin allergies/skin diseases

10. Patients with Pott’s spine/infections/other systemic diseases.

167

11. Patients with systemic conditions such as GoutyArthritis, Rheumatoid Arthritis Psoriatic Arthritis, SLE.

12. Patients with Diabetes/Hypertension

13. Bed ridden patients

14. Patients using local Anti-inflammatory medicine otherthan the research drugs.

15. Patients taking active Allopathic/Homeopathictreatment.

16. Low backache with or without radiation to legs.

17. Patients with metallic implants.

18. Subjects having any deformity of knee, hip or back.

19. History of bony or soft tissue injury to knee joint.

A patient is eligible for admission for treatment

If Sl. No. 1 – 4 is ‘Yes’ and Sl. No. 5 – 19 are ‘No’

If admitted, Sr. No. of the Subject: __________________

Date: ___________ Signature of the Investigator: ___________________

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KNEE JOINT

CASE REPORT FORM – II HISTORY

Before Treatment


1. Centre: ………………..……….






7. Address ……………………………………..……………..........…………………………








Constant sitting/standing for long hour (5)


11. Family income per months in Rs.

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12. Total family members:

13. Marital status: Single (1) Married (2) Separated (3)

Widow (4) Widower (5)

History of present illness

14. Onset of disease Acute (1) Insidious (2)

15. Duration of disease (in months)

16. Factors aggravating the disease/chief complaints __________________________

17. Factors relieving main complaints ______________________________________

18. History of past illness, having relation with present illness : Yes (1) No (0)

If yes, Specify______________________________________________________

History of past illness:

19. History of trauma/ Injury Yes (1) No (0)

If yes, specify: ________________________________________________________

20. Undergone Treatment before Yes (1) No (0)

Family History:

21. Diet: Veg (1) Non-veg (2) Lacto-ova veg(3)

Fish-veg (4)



Sannipataj (7)

23. Manas Prakriti : Sattva (1) Rajas (2) Tamas (3)

Sattva-Rajas(4) Rajas-Tamas(5) Sattva-Tamas (6)

Sama (7)

170

Chief complaints with duration:

24. PAIN

Name of joints involved:

Duration

Increased by exertion Yes/ No Yes (1) No (0)

Relieved by taking rest Yes/ No Yes (1) No (0)

Pain at rest Yes/No Yes (1) No (0)

Radiating to other parts Yes/No Yes (1) No (0)

25. STIFFNESS


Duration

Morning stiffness Yes (1) No. (0)

Lasting for an hour or so Yes (1) No. (0)

26. SWELLING


Duration

27. RESTRICTED MOVEMENTS


Duration

Crepitus Yes/No Yes (1) No. (0)

Duration

28. VARIATION IN PAIN

Climate

Season

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Day/night

Rest/movement

Walking/exertion

Other relations if any

GENERAL EXAMINATION OF THE PATIENT

29. G.C.: _____________________________

30. Pulse: _____________________________

31. B.P. : _____________________________

32. Respiratory Rate: _____________________________

33. Body weight: _____________________________

34. Pallor Present/Absent

35. Icterus Present/Absent

36. Oedema Present/Absent

37. Lymphadenopathy Present/Absent

38. Pigmentation Present/Absent

39. Deformity Present/Absent

SYSTEMIC EXAMINATION OF THE PATIENT

40. Gastro Intestinal System: _____________________________

41. Cardio Vascular System: _____________________________

42. Respiratory System: _____________________________

43. Central Nervous System: _____________________________

44. Genito Urinary System: _____________________________

45. Reticulo Endothelial System: _____________________________

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Samprapti (pathogenesis) of the disease according to Ayurvedic concept:

46. Dosa Vata (1) Pitta (2) Kapha (3)

Anubandhya dosha

Anubandh dosha

Avaraka dosha

Ksheen dosha

47. Dushya (Involved) Rasa (1) Rakta (2) Mamsa (3)


Shukra (7) Ojas (8)


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KNEE JOINT

CASE REPORT FORM – III LABORATORY INVESTIGATION


1. Centre: ………………..……….


3. Sr. No. of the subject: …………………………….........…………………………………





9. Date of Assessment :

INVESTIGATIONS PROFORMA

10. Blood Pathology

• TLC: _________________________

• DLC: _________________________

• ESR: _________________________

• Hb %: _________________________

11. Blood Bio-chemistry

• RA Factor: _________________________

• Serum calcium: _________________________

• Serum Alkaline phosphatase: _________________________

174

• Blood Urea: _________________________

• Serum Uric Acid: _________________________

• Blood-Sugar Fasting/PP: _____________/____________

• Others: _________________________

12. Radiology

• Soft Tissue swelling: _________________________

• Effusion: _________________________

• Osteoporosis: _________________________

• Erosion Cart/Bony: _________________________

• Deformity: _________________________

• Ankylosis: _________________________

• Reduced joint space: _________________________

DRUG TREATMENT GROUP-I/II

Medicine Dose & frequency Duration

SIDE EFFECTS/UNTOWARD EFFECTS IF ANY

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ASSESSMENT OF TRIAL

Grade 0 = No Symptoms

Grade 1 = Mild Symptoms

Grade 2 = Symptoms Sufficient to Cause Distress/Difficulty in performing routine work

Grade 3 = Symptoms very severe/ patient unable to perform his routine work.

Symptoms Before Treatment After Treatment(Severity Grades) (Severity Grades)

0 1 2 3 0 1 2 3

Pain

Tenderness

Swelling

Stiffness

Fatigue

Restricted Movement

Deformity

Before Treatment After Treatment

Walking Time(Seconds)

Grip Power (mm/Hg)

Pressing Power(mm/Hg)

ESR(mm/Hr)

Hb (Gm %)

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WOMAC OSTEROARTHRITIS INDEX

SECTION A

PAIN

How much you have had …………………..

1. When walking on a flat surface?

Visual Analogue Scale

1 2 3 4 5 6 7 8 9 10

2. When going up or down stairs?


1 2 3 4 5 6 7 8 9 10

3. At night while in bed? (i.e. – pain that disturbs your sleep)


1 2 3 4 5 6 7 8 9 10

4. While sitting or lying down?


1 2 3 4 5 6 7 8 9 10

5. While standing?


1 2 3 4 5 6 7 8 9 10

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SECTION B

STIFFNESS


6. How severe has your stiffness been after you first woke up in the morning?


1 2 3 4 5 6 7 8 9 10

7. How severe has your stiffness been after sitting or lying down or while resting leter in theday?


1 2 3 4 5 6 7 8 9 10

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SECTION C

PHYSICAL FUNCTION


8. When going down the stairs?


1 2 3 4 5 6 7 8 9 10

9. When going up the stairs?


1 2 3 4 5 6 7 8 9 10

10. When getting up from a sitting position?


1 2 3 4 5 6 7 8 9 10

11. While standing?


1 2 3 4 5 6 7 8 9 10

12. When bending to the floor?


1 2 3 4 5 6 7 8 9 10

179

13. When walking on a flat surface?


1 2 3 4 5 6 7 8 9 10

14. Getting in or out of a car, or getting on or of a bus?


1 2 3 4 5 6 7 8 9 10

15. While going shopping?


1 2 3 4 5 6 7 8 9 10

16. When putting on your socks or stockings?


1 2 3 4 5 6 7 8 9 10

17. When getting out of bed?


1 2 3 4 5 6 7 8 9 10

18. When talking off your socks or stockings?


1 2 3 4 5 6 7 8 9 10

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APPENDIX



KNEE JOINT

KELLGREN– LAWRENCE RADIOGRAPHIC GRADING SCALE OFOSTEOARTHRITIS OF TIBIO FEMORAL JOINT.

Grade of osteoarthritis Description

0 No radiographic findings of osteoarthritis.

1 Minute osteophytes of doubtful clinical significance.

2 Definite osteophytes with unimpaired joint space.

3 Definite osteophytes with moderate joint space narrowing.

4 Definite osteophytes with severe joint space narrowing andsubchondral sclerosis.

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Drug: Study Code:


CLINICAL VALIDATION OF GUGGULU, SHUNTI &GUDUCHI IN RHEUMATOID ARTHRITIS


184

Blank

185

I. BACKGROUND

Rheumatoid arthritis1 is a chronic multisystem disease characterized by persistentinflammatory synovitis, usually, involving peripheral joints in a symmetric distribution. The potentialof synovial inflammation to cause cartilage destruction and bone erosions & subsequent changes injoint integrity is the hallmark of the disease.

Exact etiology is unknown. Although recent work has focused on the possible role ofsuper antigens produced by a number of microorganism including staphylococci, streptococci andmycoplasma arthritidis, other possible etiology mechanism in RA include a breakdown in normal selftolerance leading to reactivity to self antigens in the joint such as type-II collagen or loss ofimmuno regulatory control mechanism resulting in polyclonal ‘T’ cell activation. Superantigens areprotein with the capacity to bind to HLA-DR molecules and particular V

â segments of the

heterodimetric T cell receptor and stimulate specific T cell expressive the Vâ gene products.

Of all the potential environmental triggers, the one only clearly associated with thedevelopment of RA is cigarette smoking. Rheumatism arthritis effect females in three times morethan males it generally occurs in late third or fourth decade of their life spans.

The Ayurvedic treatment of Amavata - Rheumatoid arthritis is being increasingly recognizedas an alternate approach to its treatment. The modern treatment of this disease is not verysatisfactory and is often attended with serious reactions. As such efforts are being persistentlymade for this dreadful disease. An important aspect of Ayurvedic treatment is its easy availabilityand abundance of its ingredients.

According to Ayurveda some of etiological factors such as Viruddhahara (Improper &irregular dietary habits), Viruddhachesta (Improper Physical and Psychological activities),Mandagni, Sedentary habits and exercise immediately after food are said to be responsible forthe origin of Amavata.


CLINICAL VALIDATION OF GUGGULU, SHUNTI & GUDUCHI INRHEUMATOID ARTHRITIS

References

1. Harrison’s Principle of Internal medicine: 15th Edition Page: 2083, Vol-II.

2. Madhav Nidana, Chapter 25,

186

Various studies on Amavata-Rheumatoid arthritis have been published in the JRAS andother scientific journals. Some of the important publications dealing with development of diseases,the Ayurvedic concepts of its etiopathogenesis, the dietetic management and effect of certaintherapies are presented in this compilation on Amavata.

The Agnimandhya-Grahani Dosa has been considered to be the main factor in pathogenesisof this disease in Ayurveda. Certain studies have been conducted and reviewed to assess thegastro-intestinal function. The findings indicate impaired secretion of gastric acid secretion, derangedliver function and reduced intestinal absorption.

The cardinal features of Amavata are swelling and pain like scorpion bite over the jointslike hands and legs (especially knee, ankle wrist, metacarpals and metatarsals). Based on thecardinal feature and other associated features, many effective regimens are described in Ayurvedicclassics.

Owing to the gravity of the situation, a need is felt for searching the safe /effectiveAyurvedic formulations to reduce the symptoms. Keeping all these view in consideration and thepublic health needs, the council intends to initiate scientific studies on well known and safe classicalAyurvedic formulation that is being successfully prescribed by Ayurvedic physicians without anyside effects since centuries.

For the present study, coded Ayurvedic drug like AYUSH-RA tab. and AYUSH-RA oilhave been taken to assess its clinical safety and efficacy.

II. OBJECTIVES

To study the effect of Guggulu, Shunti & Guduchi in rheumatoid arthritis

III. CENTRES



Sample Size : 50 cases in each center

Trial period : 18 months

Design of the study : Open observational Trial.

Drug & dosage : Tab. AYUSH-RA 2gm twice daily after food andAYUSH - RA oil for external application 2 to 3time daily.

Duration of the study : 45 days drug therapy with a follow up for 15days without drug.

187

Study period : 1 year to complete study.

Follow – Up : The follow-up will be carried out after 15 days oftreatment.


• Age between 35 - 65 years of either sex

• Presence of any four of the following seven criteria (according 1987, revised criteria ofAmerican College of Rheumatology)

(a) Morning stiffness: Stiffness in and around joints lasting one hour before maximalimprovement (More than 6 week’s duration).

(b) Arthritis of three or more joints (at lest three joint area, observed by Physiciansimultaneously having pain with soft tissue swelling or joint effusion, not just bonyover growth) (More than 6 weeks duration).

(c) Arthritis of Hand joints (More than 6 weeks duration).

(d) Symmetric arthritis (More than 6 week’s duration).

(e) Presence of Rheumatoid Nodules

(f) Serum Rheumatoid factor- positive

(g) Typical Radiographic changes of arthritis on PA view of hand & wrist radiographthat must include erosions or unequivocal bony decalcification adjacent to involvejoints.



2. Patients who develop secondary complication of RA e.g. Pleuro-pericardial disease,severely damaged joint with bed ridden patients.

3. Any other serious illness e.g. Hepatic/ renal failure.

4. Patient with diagnosed other arthritis like Gouty arthritis, tuberculosis arthritis etc.

5. Patient receiving any other method of treatment.


The cases with following complications will be withdrawn from the study.

1. Aggravation of the disease during the course of the trial period.

2. Discontinuation of the treatment during trial.

188

3. Development of any serious complications requiring change in the treatment.


• The full details of history and physical examination of the patients will be recorded as perthe proforma (Forms I & IA).

• Clinical assessment will be done and recorded on ‘0’ day, 15th day, 30th day, 45th dayand 60th day.

• Laboratory investigation will be done before and after treatment i.e. on ‘0’and 45th day.

IX. METHOD OF ASSESSMENT OF TREATMENT

The changes in the subjective and objective parameters before and after the treatment shallbe considered for assessment of the safety and efficacy the drug.

1. Clinical Assessment

Clinical assessment will be done (symptoms graded from 0 to 3) and recorded on thezero day (i.e. one day before administering the trial drug), after completion of the treatment period(i.e. on 45th day of the treatment) and on the final day of the follow-up (i.e. on 60th day).

Joint pain:

Sl. Severity of Pain Grade Score

1 No pain Zero 0

2 Pain occasional, can be managed I 2without drug

3 Pain frequent and can be managed II 4with some pain killer

4 Pain persistent and unmanageable III 6even with drugs

Morning stiffness:

Sl. Morning stiffness Grade Score

1 No stiffness Zero 0

2 Early morning stiffness upto 30 minutes I 2

3 Early morning stiffness more than 30minutes and less than 45 minutes II 4

4 Morning stiffness more than 45 minutes III 6

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Swelling:

The circumference of swollen Proximal inter Phalangeal joints (PIPj) and big / major jointsare measured with simple measuring methods (soft & thin tape). (only a maximum of 3 PIPj & 3major joints are to be measured indicating the names of the joints measured for the follow-up)

Tenderness:

Sl. Tenderness Grade Score

1 No tenderness Zero 0

2 Tender but bearable I 2

3 Tender and winced II 4

4 Tender winced and withdraw III 6

Swelling:

Sl. Severity of Swelling Grade Score

1 No swelling/not making the bony Zero 0land marks of joints

2 Just covering the bony prominences I 2

3 Considerably above the land marks II 4may be with positive fluctuation.

4 III 6

Sl. Name of the involved Measurement in mm.

joint Zero day 45th day 60th day

1

2

3

4

5

6

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2. Functional assessments

Apart from this walking time in seconds, gripping power, pressing power using inflated mercurymanometer and writing time before treatment and once in every 15 days would be recorded tillthe completion of the treatment.

a) Functional tests: To have an objective view of the improvements in the functions of theaffected joints, periodical functional tests have been done (Loxton, et al. 1952 and By-waters et.al.,1950)

• Walking time: Patients were asked to walk a distance of 150 ft. and time taken hasbeen recorded.

Sl. Walking time in seconds

Zero day 45th day 60th day

1

2

3

4

5

Sl. Walking time in seconds Grade Score

1 Zero 0

2 I 2

3 II 4

4 III 6

5 IV 8

191

• Grip power: Patients were asked to squeeze the inflated cuff up to 50 mmHg of thesphygmomanometer and the grip power has been recorded in m.ms. of mercury dependingupon the rise of mercury column.

Sl. Grip power (in mm Hg.)

1 Right hand Left hand

2 Zero day 45th day 60th day Zero day 45th day 60th day

3

4

Sl. Grip power Grade Score

1 If the scale shows between Zero 050-55 mmHg

2 between 56 - 65 mmHg I 2

3 between 66 - 75 mmHg II 4

4 between 76 - 85 mmHg III 6

5 86 mmHg & above IV 8

• Pressing power: Similarly when the patient presses the same inflated cuff up to 50 mmHgagainst a table then it is recorded as pressing power.

Sl. Pressing power (in mm Hg.)

1 Right hand Left hand

2 Zero day 45th day 60th day Zero day 45th day 60th day

3

4

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Sl. Grip power Grade Score

1 If the scale shows between Zero 050-55 mmHg

2 between 56 - 65 mmHg I 2

3 between 66 - 75 mmHg II 4

4 between 76 - 85 mmHg III 6

5 86 mmHg & above IV 8

ASSESSMENT ON BIO-CHEMICAL CHANGES

ESR and C-reactive proteins will be done before, monthly and after the treatment.

Sl. ESR (mm/1st hr) Grade Score

1 <20 Zero 0

2 21 to 40 I 2

3 41 to 60 II 4

4 61 to 80 III 6

5 >80 IV 8

ASSESSMENT OF SEROLOGICAL CHANGES

R.A. test (Latex fixation test) and Serum C-reactive protein will be done before monthlyand after treatment. The radiological changes will be assessed before and after treatment.

Sl. R.A. factor Grade Score

1 Negative Zero 0

2 Positive I 2

3 Strongly positive II 4

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Data of clinical symptoms, physiological parameters and laboratory parameters will betabulated and analyzed by using appropriate statistical methods. The data of each case will haveto be communicated on completion of trial therapy to the Statistical Officer of CCRAS through e-mail for analysis


The progress of the trial will be monitored through field visits by monitoring unit ofCCRAS. Data analysis will be undertaken at the Monitoring Unit of CCRAS.

XII. ETHICAL REVIEW


B. Data and safety monitoring board: A Data and safety monitoring board (DSMB)at Hqrs will carefully monitor the data and side effects during the period of study and put in aplace where by prompt reporting of adverse events occur. The data will be reviewed as every 20participants entered the study and administered the trial drugs. The research team will reportimmediately to the PI and Data Monitoring Board 1) any life threatening conditions whether theyare perceived to be study related or not. The Board decides whether the adverse effects warrantdiscontinuation of the study protocol. Protocols will be written and approved for the treatment ofstudy related adverse events


A consolidated amount of Rs. ………. /- per visit will be given i.e., on the 1st day ofrecruitment after screening, 15th day, 30th day 45th day and 60th day.


Short-term two-day training will be provided to the Investigators involved in themulticentric trial at CCRAS Hqrs. New Delhi. The investigators will be detailed about the clinicaltrial conduct and laboratory procedures in order to maintain the uniformity.



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CONSENT FORM




Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical validation of guggulu, shunti & guduchi in rheumatoid arthritis.





Relationship ___________________________________


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Arthritis is a vague and common terminology which literally means inflammation of thejoints. There are many types of arthritis which are generally grouped into three i.e. infective,immunological and Degenerative. Arthritis is a global problem since the generation of mankind.The incidence is on increase as a consequence of the fact developing science and technology,which makes the man immobile even in midst of his comforts. The sedentary life style predisposesmore. India is no exception. Rheumatoid arthritis falls under immunological disorders. It s adisabling disease and the disability is so great that suffers become physically crippled and becomesinvalid in family and society. It occurs in all climates, on all ethnic groups in the world indeveloping countries it is estimated that 3% of the population is suffering. It affects the femalethree times more than males. It generally occurs in late third or fourth decade of their life spansand finally cripples the sufferers with deformities. Ayurvedic system also recognizes this clinicalentity as Amavata.

The coded drug AYUSH-RA tab. and AYUSH-RA oil are to be tried in Rheumatoidarthritis.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 60 days. During this period, you areexpected to visit once in a 15 days during drug treatment and follow up period.

Before you start the treatment, clinical assessment and the Biochemical tests will be carriedout. If your diagnosis is confirmed and if you are a fit case you will be subjected to this study forthe period of 60 days. You will be supplied with the sufficient quantity of medicines to last untilyour next visit i.e. once in every 15 days. The clinical assessment and the laboratory investigationswill be done before and after treatment for the therapeutic efficacy of the drug.


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CASE RECORD FORM I – SCREENING

BEFORE TREATMENT


CASE REPORT FORM-I: SCREENING

1. Centre: ………………..……….





6. Postal Address ………………………….....………..………………………………………


1. Age between 35 - 65 years

2. Presence of any four of the following seven criteria(according 1987, revised criteria of AmericanCollege of Rheumatology)

(a) Morning stiffness: Stiffness in and around jointslasting one hour before maximal improvement(More than 6 week’s duration).

(b) Arthritis of three or more joints (at lest three jointarea, observed by Physician simultaneously havingpain with soft tissue swelling or joint effusion, notjust bony over growth) (More than 6 weeks duration).

(c) Arthritis of Hand joints (More than 6 weeks duration).

(d) Symmetric arthritis (More than 6 weeks duration).

197

(e) Presence of Rheumatoid Nodules

(f) Serum Rheumatoid factor- positive

(g) Typical Radiographic changes of arthritis on PAview of hand & wrist radiograph that must includeerosions or unequivocal bony decalcification adjacentto involve joints.



4. Patients who develop secondary complicationof RA e.g. Pleuroperi cardial disease, severelydamage joint with bed ridden patients.

5. Any other serious illness e.g. Hepatic/ renal failure.

6. Patient with diagnosed other arthritis like Gouty arthritis,tuberculosis arthritis etc.

7. Patient receiving any other method of treatment.

If Yes to Sl. No. 1 & 2 and No to Sl. No. 3 to 7 above, admit the subject to the trial.

If admitted, subject serial No. __________________


Date:____________ Signature of the Doctor _______________________

198




1. Centre: ………………..……….






7. Address ……………………………………..……………..........…………………………








Total income of the family (in Rs.) ...........................................................

199

HISTORY OF PRESENT ILLNESS:

Chief complaints with duration (in days)

Yes (1) No (0) Duration(in days)

10. Pain in Joints

If present, specify three major and three minor joints

11. Swelling in joints


12. Morning stiffness

13. Tenderness

14. Fever

FUNCTIONAL ASSESSMENT

15. Walking time (in seconds) __________________

16. Grip power in mm Hg:

Left hand Right hand

17. Pressing power in mm Hg



19. Previous episodes Yes (1) No (0)

20. Duration of disease (in days)

Personal History:

21. Diet: Veg (1) Non-veg (2) Lecto-veg (3)

200

Addiction

22. Smoking Yes (1) No (0)

If yes specify: (a) Quantity [packs] _____________________

(b) Total Duration in years ________________

23. Tobacco Yes (1) No (0)

If yes specify: (a) Quantity_______________________

(b) Total Duration in years____________

24. Alcohol Yes (1) No (0)

If yes specify: (a) Quantity (ml) _________


25. Any other (specify) ________________

26. Menstrual history: Regular (1) Irregular (2)

If irregular, Specify___________________________

27. Duration of menstruation: Up to 5days (1) 5-7 days (2)

More than 7 days(3)

28. Quantity Normal (1) Abnormal (2)

If abnormal, Specify__________________________________

29. Prakriti: Vata (1) Pitta (2) Kapha(3)

Vata-Kaphaj (4) Vata-Pittaja (5) Pittaja-Kaphaja(6)

Sannipataj (7)


30. Height: ___________________

31. Weight: ___________________

201

32. Pulse (per min) ____________

33. Blood Pressure (mm Hg) ___________

34. Body temperature (o F) _____________

35. Respiration rate (per min) _____________

36. Abnormal breathing sounds, specify____________


37. CVS

If abnormal, details_____________________________________________

38. CNS






41. Urogenital system


42. Vision


Date: ______________ Signature of Investigator: ______________________

202




(On 0th Day)

1. Centre: ………………..……….










8. Pain in Joints





11. Tenderness

12. Fever

203



14. Grip power in mm Hg




Date: ______________ Signature of Investigator: _________________________

204




(On 15th Day)

1. Centre: ………………..……….









7. Pain in Joints

8. If present, specify three major and three minor joints




12. Tenderness

13. Fever

205








206




(On 30th Day)

1. Centre: ………………..……….









7. Pain in Joints





12. Tenderness

13. Fever

207








208




(On 45th Day)

1. Centre: ………………..……….









7. Pain in Joints





12. Tenderness

13. Fever

209








210




(On 60th Day)

1. Centre: ………………..……….









7. Pain in Joints





10. Tenderness

11. Fever

211








212



FORM IV – LABORATORY INVESTIGATIONS

(0th day)

1. Centre: ………………..……….







8. Stage of Assessment

Initial 4th week 8th week 12th seek

9. Urine Examination:



Routine _____________ Microscopic____________

Ova/Cyst____________ Occult Blood____________

Blood Examination

11. TC (Cells/Cmm.): ______________________

12. DC P (%)______ L(%) ______ E(%)______M (%)_____B(%)______

13. Hb (g/dl) ____________________________

213

14. ESR (1st hour.)(mm) ____________________

15. Blood Sugar – PP (mg./dl): _______________

16. B.Urea (mg./dl): _____________________

17. S.Creatinine (mg./dl) _______________

18. Uric acid (mg./dl) ______________

19. C. Reactive protein _____________

20. RA factor (Latex fixation test)_____________

21. SGOT _________________

22. S.G.P.T _________________

23. S. Alkaline phosphatase ________________

24. Serum Bilirubin. ________________

25. X-ray chest PA view_________________

26. ECG 12 leads _________________

27. X-ray hand/foot/ limbs (before & after treatment) _________________

28. Any other Remarks _________________________________________________

214



FORM IV – LABORATORY INVESTIGATIONS

(60th day)

1. Centre: ………………..……….







8. Stage of Assessment

Initial 4th week 8th week 12th seek

9. Urine Examination:



Routine _____________ Microscopic____________


Blood Examination

11. TC (Cells/Cmm.): ______________________

12. DC P (%)______ L(%) ______ E(%)______M (%)_____B(%)______

13. Hb (g/dl) ____________________________

215

14. ESR (1st hour.) (mm) ____________________

15. Blood Sugar – PP (mg./dl): _______________

16. B.Urea (mg./dl): _____________________

17. S.Creatinine (mg./dl) _______________

18. Uric acid (mg./dl) ______________

19. C. Reactive protein _____________

20. RA factor (Latex fixation test)_____________

21. SGOT _________________

22. S.G.P.T _________________

23. S. Alkaline phosphatase ________________

24. Serum Bilirubin. ________________

25. X-ray chest PA view_________________

26. ECG 12 leads _________________

27. X-ray hand/foot/ limbs (before & after treatment) _________________

Any other Remarks _________________________________________________

216



CASE RECORD FORM V

CONSOLIDATED DATA ON PERIODICAL OBSERVATIONS

1. Centre: ………………..……….






Sl Subjective/ 0 day/BT 15th day 30th day 45thday 60th dayTobjective Dt. Dt. Dt. Dt. Dt.Parameters

Yes No Yes No Yes No Yes No Yes No(1) (0) (1) (0) (1) (0) (1) (0) (1) (0)

1. Pain in joints

2. Swelling injoints

3. Morningstiffness

4. Tenderness

5. Fever

6. Walking time(in second)

7. Grip powerin mm Hg

217

8. Pressing powerin mm Hg

9. Other Associated Symptoms if Any [Specify]

10. Adverse reactions

11. Burning Notsensation in applicableabdomen

12. Nausea Notapplicable

13. Diarrhoea Notapplicable

14. Skin rashes Notapplicable

15. TC (Cells/Cu.mm.)

16. DC (%) 13. P 13. P14. L Not Not Not 14. L15. E applicable applicable applicable 15. E16. M 16. M17. B 17. B

17. ESR (mm / Not Not Not1st hour.) applicable applicable applicable

18 Hb (g/dl)(Cyanomethamoglobinmethod)

19. C. Reactiveprotein

20 RA factor (Latexfixation test)


22. S. Bilirubin

218

23. Total (mg/dl)

24. Direct (mg/dl)

25. SGPT (IU/L)

26. SGOT (IU/L)

27. S. Alkaline Not Notphosphatase Applicable Applicable(U/L)

28. S. Proteins(Total) (g/dl)

29. Albumin (g/dl)

30. Globulin (g/dl)


32. Blood urea Not Not(mg/dl) applicable applicable

33. S. Creatinine(mg/dl)


Routine Not NotAlbumin (g/dl) applicable applicableGlobulin (g/dl)

MicroscopicRBC Not NotPus Cells applicable applicableEpithelial Cells

35. Stool Examination

Occult Blood Not Notapplicable applicable

Ova/Cyst Not Notapplicable applicable

MicroscopicRBC Not NotPus Cells applicable applicableEpithelial Cells

219






Continuing: (1)

Drop out (2) Reason: _____________________________

Died (3) Cause: _______________________________

Date: ______________ Signature of the investigator ___________________

Name of the investigator ______________________

220


DRUG COMPLIANCE REPORT FORM – I


(To be filled by the trial participant)

(To be issued on 1st visit – 0 day and taken back on 2nd visit –15th day)

Registration No. of participant .....................................................................................................

Name of the participant ..................................................................................................................

Please come for next visit on ................................. (Date and time is to be filled by the Investigator)

Instructions to trial participant

• Please take tab. AYUSH-RA 2 gm. twice a day after food with a glass of luke warm water(approx. 250 ml.) maintaining 12 hours gap in between.

• Please return the empty strip after taking medicine along with the compliance report dulyfilled.

• Please come with empty stomach and bring breakfast along with you during next visit.

Day Date Morning dose (around 9 AM) Evening dose (around 9 PM)

Please put � Please enter Please put � Please entermark after the time mark after the timetaking the taking themedicine medicine

1.

2.

3.

4.

5.

221

Name of the participant .....................................................................

Date: ...........................................

Signature or Thumb impression of the participant ........................................

Signature of the Investigator with date ..........................................

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

222


DRUG COMPLIANCE REPORT FORM – II



(To be issued on 2nd visit – 16th day and taken back on 3rd visit –30th day)










16.

17.

18.

19.

20.

223


Date: ...........................................



21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

224


DRUG COMPLIANCE REPORT FORM – III



(To be issued on 3rd visit – 31st day and taken back on 3rd visit –45th day)










31.

32.

33.

34.

35.

225

36.

37.

38.

39.

40.

41.

42.

43.

44.

45.


Date: ...........................................



226


DRUG COMPLIANCE REPORT FORM – IV



(To be issued on 3rd visit – 46th day and taken back on 4th visit – 60th day)










46.

47.

48.

49.

50.

227


Date: ...........................................



51.

52.

53.

54.

55.

56.

57.

58.

59.

60.

229

Drug: Study Code:


PROTOCOL FOR DOUBLE BLIND CLINICAL TRIALFOR THE TREATMENT OF OSETOPOROSIS


230

Blank

231

I. BACKGROUND

Pommer coined the term osteoporosis in 1885, which literally means increased porosity ofBones.

It is described as a systemic skeletal disease characterized by low bone mass and microarchitectural detoriation of bone tissues with a consequent increase in bone fragility and susceptibilityto fracture. The magnitude of the problem has not been fully understood and the incidence ofosteoporosis is highly increased due to increased life span and greater awareness of the diseasesince 1980 (Rosen et al, 1997). In recent study the following observations were made.

1) Osteoporosis1 occurs both in males and females in India.

2) Osteoporotic fractures occur more commonly in Indian males than females.

3) Osteoporotic fractures occur 10-20 years earlier in Indian men and women compared towest (Wali, T.P. etal)

Certain factors like Genetic, personal life style factors like smoking, alcoholism lowerintake of calcium, non-exposure to sunlight and certain diseases predispose this disease.

In Ayurveda under the heading “Asthi kshaya” many signs and symptoms described canclosely be correlated with this clinical entity. This has also been treated with herbal and herbominerals since very remote past. In recent years the advancement in the field of Phytochemistryand clinical trials, it has been evinced the role of certain herbals like Cissus quardrangularis in thetreatment of bone fracture. The phytochemical studies have also established the presence ofphytosterol, phytoestrogen and calcium. Embica officinalis is an anti-oxidant and thereby stabilizesVitamine-D metabolites or their conjugates present in the primary ingredient. Further it isconsidered to promote collagen metabolism by virtue of its Vitamine-C like activity. Nowcombination of Asthi Shrankhala( Cissus quardrangularis) and Amalki( Embica officinalis ) isbeing taken up for study.


PROTOCOL FOR DOUBLE BLIND CLINICAL TRIAL FOR THETREATMENT OF OSETOPOROSIS

References

1. Harisson’s Principles of internal medicine, Volume-1, 14th Edition, International Editions, 1998, Publishedby McGraw-Hill CompaniesInc.pp1208-1209

2. Bhaisajya Ratnavali, Chaukhamba Sanskrit Samsthan, Varanasi

232

In modern medicine this disease is managed with, Hormone replacement therapy and alsowith calcium and Vitamin ‘D’ which is considered as anti resorptive and stimulator of Bone turnover. But these drugs do have side effects like nausea, vomiting and diarrhea. In this contest thenatural calcium, which is safe, less toxic, and does not have any side effect will be taken forstudy.

II. OBJECTIVES:

To assess the therapeutic efficacy of an Ayurvedic coded trial drug AYUSH B-caps in thetreatment of osteoporosis in comparison with standard control drug Calcium with Vitamin- D3.

III. CENTRES



Groups : Two – trial and control [50 (25 male and 25 female) casesin each group (Control drug will be made similar to trialdrug and one placebo draggee will be prescribed afterdinner)

Group-I : Trial drug

Group-II : Control drug

Trial Design : Double blind randomized

Drug/Dosage/Duation:

Trial drug : Coded drug AYUSH B –Two caps 500 mg each twice aday.

Control drug : Control drug 500 mg twice a day.

Duration of : One yearTreatment

Period of Study : One year for each case.

Total duration : will be Two years to complete the study.


1. Age: Patients of both sexes above 45 years and up to 70 years.

2. B.M.D. T. Score below – 1.5

233

The cases for carrying out BMD T Score will be screened with the following targetedpatients:

1. Post menopausal woman with early menopause (40 years and below) and familialprevalence.

2. Patients with osteopenia or spinal deformities on spine-x-rays.

3. Patients on long-term cortico steroids for more than six months.

4. Patients with history of osteoporosis related fractures.


1. Age below 45 and above 70

2. T. Score below –1.5

3. Primary Hyper parathyroidsim

4. Thyrotoxicosis

5. Addison’s disease

6. Cushing syndrome

7. Rheumatoid arthritis

8. Malabsorption syndrome

9. Chronic liver diseases

10. Organ transplantation

11. Chronic renal failure

12. Prolonged immobilization

13. Diabetes (Uncontrolled)

14. Cases undergoing treatment for osteoporosis

15. Cases undergoing treatment for any other serious illness.


During the course of the trial there may be certain potential adverse threats like Kidneystones, hypocalcaemia with renal insufficiency (milk alkali syndrome) and interference of calciumwith other essential nutrients. If any other side effects and other symptoms are observed then thetrial drugs will be withdrawn and will be treated symptomatically.

234


Clinical assessment will be done (O), at the end of 1st, 2nd and every subsequent monthtill the completion of treatment (Form 2). The Lab investigations (Biochemical markers) will berecorded before drug administration (O month) and after every two months till the completion oftrial (0, 2nd, 4th, 6th, 8th, 10th and 12th months i.e. the end of the treatment). The B.M.D. will bedone before and after the completion of the treatment.

IX. CRITERIA FOR ASSESMENT

30% or more in B.M.D. T. Score (above –1.5 level) increase will be considered assignificant improvement. .


Data on BMD T-Score will be analyzed using appropriate statistical tools. (NullHypothesis: There is no significant difference between the BMD T-score in the treated group andcontrol group).


CCRAS, HQ’s Office New Delhi will monitor the progress of the trial

XII. ETHICAL REVIEW

Clearance certificate from Institutional Ethical Committee (IEC) or Head of the Institutionshould be obtained before the Project is initiated. IEC/Head of the Institution should submitpatient’s information sheet and informed consent form along with project proposal for approval.Both of these forms should be maintained in duplicate with one copy given to the patient at thetime of entry to the trial.

The change between two BMD can be expressed in the form of (%) percentage between two measurementsor by absolute change in gm/cm between two measurements.

Percentage change is calculated as I BMD – II BMD x 100

I BMD

= (%) percentage change.

Absolute change is calculated as I BMD – II BMD

Absolute change

235


A consolidated amount of Rs. ___________ per visit.


Short-term two-day training will be provided to the Investigators and Laboratorypersonnel involved in the trial at CCRAS Hqrs. The investigators and technicians will be detailedabout the clinical trial conduct and laboratory procedures in order to maintain the uniformity.



236


PROTOCOL FOR DOUBLE BLIND CLINICAL TRIAL FOR THETREATMENT OF OSETOPOROSIS





Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the “Double blind clinical trial for the treatment of Osetoporosis”.





Relationship ___________________________________


237


DOUBLE BLIND CLINICAL TRIAL FOR THE TREATMENT OFOSETOPOROSIS



Osteoporosis is characterized by increased fragility and susceptibility to fracture. It is adisease very common and there is increase in its incidence due to increased life span andadvancement in health delivery system. Osteoporotic fractures occur 10-20 years earlier in Indianmen and women compared to west. The life style changes have also bearing on the predispositionof this disease. In Ayurveda system also the management is done through herbal medicines andthis clinical entity can be correlated with Asthi Kshaya. The drugs which are used for the treatmentof Osteoporosis some time causes side effects. In Ayurveda the efficacy of herbal drugs like AsthiShrankhala and Amalki have been observed in clinical trials.and now these drugs are being takenupfor study with modern medicine calcitrol in 100 cases (50 each group)


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately one year to complete. During thisperiod, you are expected to visit the hospital thirteen times. The interval between the first andsecond visit will be around one month. After it, you are required to visit once in a month till thecompletion of the treatment.

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination, BMD Test (Bone Mineral Density). This is to make sure that you are eligiblefor the study.

If you were found eligible, you would be put on trial treatment for one year. The dailydosage will be 500mg twice. At each visit, you will be supplied with sufficient quantities of drugsto last until your next visit. On completion of the treatment B.M.D. will be done again to asses theeffect of the treatment. Bio-chemical investigations will also be carried out one in every twomonths.


238


DOUBLE BLIND CLINICAL TRIAL OF AYURVEDIC FORMULATION INTHE TREATMENT OF OSETOPOROSIS



1. Centre: ………………..……….





6. Address ……………………………………..………………………………………


1. Age between 45 and 70 years of either sex

2. Bone Mineral Density (B.M.D.)

CRITERIA OF EXCLUSION Yes (1) No (0)

3. Age below 45 and above 70

4. Primary hyper parathyroidsim

5. Thyrotoxicosis

6. Addison’s T. Score >-1.5 and <.4

7. Cushing syndrome

8. Rheumatoid Arthritis

9. Mal-absorption syndrome

10. Chronic liver diseases

239

11. Organ Transplantation

12. Chronic renal failure

13. Prolonged immobilization

14. Uncontrolled Diabetes

15. Cases undergoing treatment for osteoporosis

16. Cases undergoing treatment for any other serious illness

If ‘Yes’ to 1 and 2 & ‘No’ to 3 – 16 above, admit the subject to the trial. If admitted,

Subject serial No. ____


Date:____________ Signature of the Doctor ___________________

240


DOUBLE BLIND CLINICAL TRIAL OF AYURVEDIC FORMULATION IN THE

TREATMENT OF OSETOPOROSIS


1. Centre: ………………..……….






7. Address ……………………………………..……………..........…………………………








Addiction No (0) Yes (1)

10. Smoking

If yes specify: (a) Quantity (packs) _______________

(b) Total Duration in year’s _________

241

11. Tobacco

If yes specify: (a) Quantity ________________

(b) Total Duration in year’s _________

12. Alcohol

If yes specify: (a) Quantity (in ml/day) _________--_____

(b) Total Duration in year’s _________--_____

13. Prakriti: Vata (1) Pitta (2) Kapha (3)

Vata-Kaphaj(4) Vata-Pittaja(5) Pittaja-Kaphaja(6)

Sannipataj (7)


14. Height (cm) ____________

15. Weight (kg) ____________

MEDICAL HISTORY No (0) Yes (1)

16. Pathological Fracture(After the age of 40 yrs or more)

If yes indicate: Date_______ Site__________ History of pain before fracture_________

17. Family History of Osteoporosis

If yes indicate relationship_______________________________________

18. Spinal Deformity

If yes indicate site_________ Date from which suffering__________

Menstrual History (For female patients): No (0) Yes (1)

19. Age in years at Menarche

20. Duration of menstrual period in days

21. Interval of menstrual period

22. Age in years at onset of menopause

242

SURGICAL HISTORY No (0) Yes (1)

23. Abdominal Surgery

24. Hysterectomy

25. Oophorectomy

26. Orthopedic Surgery

Drugs used (having bearing on Osteoporosis) No (0) Yes (1)

27. Steroids

If yes indicate duration (in months) _______ Doses_______

28. Anti convulsive

If yes indicate duration (in months) _______ Doses________

29. HRT Heparin/Warfarin

If yes indicate duration (in months) _______ Doses________

Clinical Symptoms No (0) Yes (1)

30. Skeletal Pain

If yes indicate Region______________ Duration in months ________

31. Kyphosis

32. Other clinical symptoms

If yes, specify (Symptoms & Duration) ________________________________________

33. Type of pain Acute (1) Chronic (2)

Date:_______________ Signature of the Investigator_________________

243


DOUBLE BLIND CLINICAL TRIAL OF AYURVEDIC FORMULATION IN THE

TREATMENT OF OSETOPOROSIS


1. Centre: ………………..……….







8. Month of Assessment :

Initial (0) 1st month (1) 2nd month (2)

3rd month (3) 4th month (4) 5th month (5)

6th month (6) 8th month (7) 9th month (8)

10th month (9) 11thmonth (10) 12th month (11)

Clinical Symptoms No (0) Yes (1)

9. Skeletal Pain

If yes indicate Region______________ Duration in months ________________

10. Kyphosis

11. Other clinical symptoms

If yes, specify (Symptoms & Duration) _______________________________________

12. Type of pain Acute (1) Chronic (2)

Date: ___________ Signature of the Investigator _______________________

244


DOUBLE BLIND CLINICAL TRIAL OF AYURVEDIC FORMULATION IN THETREATMENT OF OSTEOPOROSIS

CASE REPORT FORM IV-A – LABORATORY INVESTIGATIONS

1. Centre: ………………..……….








Initial (0) 2nd month (1) 4th month (2)

6th month (3) 8th month (4) 10th month (5)

12th month (6)

9. Serum Calcium__________________________________(mEg / 100 cc)

BONE TURNOVER

10. Alkaline phosphate________________________________(King & Amstrong units)(Bone specific)

11. Osteo calcin (BGP) ________________________________(King & Amstrong units)

12. Procollagen peptides________________________________

BONE RESORPTION

13. Pyridinium cross links and some of________________________________

Type – I Collagen Break down products in serum

14. Serum Tartarate resistant________________________________________

Acid phosphatase

Date: _____________ Signature of the Investigator: ______________

245

ANORECTAL DISORSERS

SEC

TIO

N - IV

246

Blank

247

Drug: Study Code:


MULTI CENTRIC OPEN CLINICAL TRIAL ON THEMANAGEMENT OF FISSURE-IN-ANO (PARIKARTIKA)


248

Blank

249

I. BACKGROUND

An Anal Fissure is a tear in the skin around the opening of the Anus1. It can cause sharppain, especially when opening the bowels. Anal Fissure is thought to be a common disorder forwhich many people do not seek medical advice. The internal anal sphincter is thought to play akey role in the development of an Anal Fissure. This is one of two muscles that control theopening of the anus. Both muscles need to relax in order to pass a stool. Unlike the exterior analsphincter, which can be tensed or relaxed voluntarily, there is no voluntary control of the internalsphincter. Because of the pain of a fissure, the internal anal sphincter may go into spasm - causinga raised pressure within the anus. This excess pressure makes it harder to pass a stool, makingconstipation worse, and contributing to a vicious circle. The spasm of the internal anal sphinctercan also restrict the blood supply to the anal skin, which reduces its ability to heal.

The condition Parikartika has been mentioned in the Ayurvedic literature as one of thefifteen kinds of disorders which may result from an injudicious use of purgatives owing to theignorance of the physician or of the patient. Improperly done virechana karma (purgatives)aggravates the Vata & Pitta that gives rise to a sort of cutting, sawing pain in the anus, penis,umbilical region and the neck of the bladder (Vasti). The omission of flatus is arrested the Vayulies incarcerated in the abdomen and relish for food vanishes.

Application of Creams or Ointments that contain local anaesthetics (eg lidocaine) orsteroids (eg hydrocortisone) and an injection of outline toxin (Botox), anal dilatation,sphincterotomy, and fissurectomy (chronic fissure) are usually in practice. But these procedureshave sometimes associated with some complications like post operative anal stenosis, sphincterincontinence etc. To overcome such problems and to provide cheap, simple, ambulatory andeffective treatment, different treatment modalities have been kept on trial on the basis of thetreatment mentioned in the ancient literature and also based on the preliminary work done in themanagement. Earlier workers have tried Kaseesadi Taila Vasti, Jatyadi Ghtrita per rectalapplication, hot sitz bath and a laxative, taking lead from the ancient classics especially descriptionsdescribed about the use of Picchavasti and Anuvasana Vasti in the treatment of parikartika.Though different regimens have proved to be efficacious in the treatment of fissure-in-ano, patients


MULTI CENTRIC OPEN CLINICAL TRIAL ON THE MANAGEMENT OFFISSURE-IN-ANO (PARIKARTIKA1)

References

1. Charak Siddhi sthana 6/29

250

feel difficulty in pushing of Kaseesadi Taila in to the anal canal. Sometimes there was animmediate spillage of oil after pushing due to spasm of the sphincter. More over it was founddifficult to assess which procedure was more effective in the combined therapy of pushing of oiland application of ghee manually per rectally. In order to see the efficacy of various proceduresindividually, it was thought to try different therapeutic regimens in present study beside thedevelopment of a novel method of dilatation of anal canal to see the effect of different procedures/ drugs in the management of fissure-in-ano.

II. OBJECTIVES

• To provide symptomatic relief in shorter duration

• To provide healing to the fissure-in-ano

• To find out a simple, amble, safe & cost effective therapeutic regimen or procedure in themanagement of fissure-in-ano

III. CENTRES

CCRAS identified Centers.



Trial Drug /Dosage :

Group: I

• Triphala churna; 5gm with warm water daily at bedtime for 28 days

• A novel method of Anal dilatation for 07 days

• Hot Sitz bath for 28 days Anal dilatation:

A self retaining Foley’s rubber catheter no. 18 is smeared with 2% lignocaine jelly andinserted in the anal canal up to 4 cm. from the tip and on the first day the bulb is inflated with 5ml of water and gently pull the catheter downward till it sustains maximum resistance and thecatheter is allowed to stay in position for one minute. Then the water is withdrawn from the bulband the catheter is removed from the anal canal. After removing the catheter the patient is givenhot sitz bath for two minutes. The catheter is sterilized properly and reused in the same patient fornext sittings.

The procedure remains unchanged except in the increase in the volume of the water from5ml to different volumes as indicated below:

Day 1 : 5ml

251

Day 2 : 7ml

Day 3 : 10ml

Day 4 : 15ml

Day 5 : 20ml

Day 6 : 20ml

Day 7 : 20ml

Group: II

• Triphala churna; 5gm with warm water daily at bed time for 28 days

• Anal dilatation with Jatyadi Ghrita for 07 days

• Hot Sitz bath for 28 days

Anal dilatation:

Take sufficient quantity of Jatyadi Ghritam in a sterile bowl. Initially the little finger (goved)is well smeared with the Ghritam and gently inserted in the Anal Canal watching the resistanceproduced by the sphincter. Care should be taken to push the finger always against the non-ulcerwall of the Anal Canal and inwards. After the little finger is inserted in to the canal allow to remainthe finger in the canal for one minute. Then the finger is withdrawn slowly and then index finger isinserted following the same principle and wait for two minutes. Then index and middle fingers areinserted together and kept for three minutes in the canal. Care should be taken that the fingersand the anal canal are well lubricated with the Ghritam. After the procedures are completed thepatient is allowed hot sitz bath for three minutes. The same procedure is to be carried out forseven days.

Group: III

• Triphala Churna; 5gm with warm water daily at bed time for 28 days


• Application of Jatyadi Ghrita (P/R) (without dilatation) for 07 days

Application of Jatyadi Ghrita (P/R)

The patient is first asked to take hot sitz bath then with the help of gloved little finger theJatyadi Ghritam is applied gently in the Anal Canal without applying much pressure in the Canal.The same procedure is to be carried out for seven days.

252

Duration of the trial : Total six weeks: (28 days as per the schedulegiven under each group and last two weeksfollow-up without any medication.

Design of the Study : Open trial


Selection of cases : Any age of either sex with complains of Pain with or withoutbleeding per rectum during and/or after the defecation with or without other symptoms like, itching,discharge, constipation, with /or without pain are examined and confirmed by peri-analexamination are admitted for the study.

The cases are randomly selected irrespective of age, sex, chronicity, Prakriti and type offissure.


The cases associated with malignancy were excluded from the study.

VII CRITERIA FOR WITHDRAWAL

During the course of the trial treatment, if any serious condition or any serious adverseevents which requires urgent treatment or if patients themselves want to withdraw from the study,such subjects may be withdrawn from the trial.


The full details of screening, history and physical examination of the subjects will berecorded as per case record form I & II. Clinical and physiological assessment in form III andlaboratory investigations in forms IV will be done regularly.

IX. CRITERIA OF ASSESSMENT

Since the pain is the main symptom in Fissure-in-ano, a total number of days taken toheal the ulcer with alleviation of pain and associated symptoms are noted and results are assessedin the following manner.

Sl. Response Response DescriptionDuration

1 Complete < 7 days When there is complete relief in pain during/afterResponse defecation without any bleeding within 7 days of the

therapy started. No recurrence thereafter up to 6 weeksof the follow-up.

253

2 Partial 08 – 14 When there is complete relief in pain during/afterResponse days defecation without bleeding after 7 days but before 14

days of the therapy and no recurrence thereafter up to 6weeks of the follow-up.

3 Poor 15 – 21 Complete relief in pain after 14 days but before 21 daysResponse days of the treatment without bleeding and recurrence

thereafter up to 6 weeks of the follow-up.

4 No 22 days & When there is any relief in pain or partial relief or reliefResponse above in pain after 22 days of the therapy and/or recurrence

thereafter.

5 Drop-out Drop-out Discontinuation of the treatment during the trial due todevelopment of any complications & aggravation of thedisease.


Data on intensity of pain, duration of pain will be tabulated and analysed by usingappropriate statistical methods.

However the data of each case will have to be communicated on completion of trialtherapy to the Statistical Officer of CCRAS through e-mail.


The progress of the trial will be monitored by field visits by monitoring unit of CCRAS.Data analysis will be undertaken at the Monitoring Unit of CCRAS.


A. Ethical Committee (IEC): The proposal will be placed before Ethical Committee(IEC) of trial center for getting clearance certificate before the project is initiated. Patient’sinformation sheet and informed consent form will be submitted along with project proposal forapproval by IEC. Both will be maintained in duplicate with one copy given to the patient at thetime of entry to the trial.

B. Data and Safety Monitoring Board: A Data and safety monitoring board (DSMB)at Hqrs. will carefully monitor the data and side effects during the period of study and put in aplace where by prompt reporting of adverse events occur. The data will be reviewed as every 20participants entered the study and administered the trial drugs. The research team will reportimmediately to the PI and Data Monitoring Board 1) any life threatening conditions whether theyare perceived to be study related or not. The Board decides whether the adverse effects warrant

254

discontinuation of the study protocol. Protocols will be written and approved for the treatment ofstudy related adverse events


A consolidated amount of Rs.______ /- per visit i.e., on the 1st day of recruitment afterscreening, 3rd week, & 6th week (3 times)




The Laboratory Investigations (Pathological/Biochemical, etc.), which are not available atresearch Institutes should be conducted at identified reputed Tabs /Government Institutes underintimation to this Council observing requisite codal formalities.

255





Date: _______________ Signature of the Investigator ___________

Name: ____________________________

CONSENT BY SUBJECT

I have been informed to my satisfaction, by the attending physician, the purpose of the

clinical trial and the nature of drug treatment and follow-up, including the laboratory investigations

to be performed to monitor and safeguard my body functions.

I am also aware of my right to opt out of the trial at any time during the course of the trial

without having to give the reasons for doing so. I am willing to undergo any risk for inclusion in

this study.

I, exercising my free power of choice, hereby give my consent to be included as a subject

in the clinical trial on “Multi centric open Clinical trial on the management of Fissure-in-

ano (Parikartika).”





Relationship ___________________________________


256


MULTI CENTRIC OPEN CLINICAL TRIAL ON THE MANAGEMENT OFFISSURE-IN-ANO (PARIKARTIKA)


What is the study about? What is an Anal Fissure?

An anal fissure is a small tear in the lining of the Anal Canal. This type of tear maydevelop in adults from passing hard or large stools during bowel movements. Anal Fissure is alsocommon in infants between 6 and 24 months. Anal Fissures are less likely to develop in olderchildren.

An Anal Fissure may cause you to experience pain and bleeding. More than 90 percentheal without surgery, and you can use topical creams or suppositories to provide relief as theyheal. Anal fissures that fail to heal may become chronic and cause considerable discomfort. CertainAyurvedic formulations and procedures were proved to be effective in the management of fissure-in-ano.

What are signs and symptoms of an anal fissure?

The main signs and symptoms of an anal fissure include:

• Pain or burning during bowel movements that eases until the next bowel movement

• Bright red blood on the outside of the stool or on toilet paper or wipes after abowel movement

• Itching or irritation around the anus

• A visible crack in the skin around the anus

When to see a doctor?

See your doctor if you have pain during bowel movements or blood on stools or toiletpaper after a bowel movement.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately six weeks. During treatment period,you are expected to visit the hospital daily from day one to seven days then on 14th, 21st, 28th,35th & 42nd day.

257


If you are found eligible, you would be put on trial treatment for six weeks.

At each visit, you will be supplied with sufficient quantities of drugs to last until your nextvisit. If any adverse reactions like skin allergy, nausea, vomiting and palpitation/tremor etc., noticedduring the treatment period, this should be noticed to the doctor who is treating you.


258



CASE RECORD FORM I – SCREENING

BEFORE TREATMENT


CASE REPORT FORM-I: SCREENING

1. Centre: ………………..……….





6. Address ……………………………………..………………………………………


1 Pain or burning sensation during or after defaecation

2 Bleeding per rectum during or after defaecation

3 Associated with Itching or irritation around the anus

4 A visible crack in the skin around the anus (Fissure-in-ano)

5 Bright red blood on the outside of the stool or on the toilet paper

6 Constipated bowels

CRITERIA OF EXCLUSION:

7 History of malignancy


If Sl. No. 1 – 6 is ‘Yes’ and Sl. No. 7 are ‘No’

If recruited, subject serial No: ______________

Date: __________________ Signature of the investigator: _______________________

259





1. Centre: ………………..……….







8. Address ……………………………………..……………..........…………………………

9. Educational status: Illiterate 1 Read and Write 2 Primary School 3

Middle School 4 High School 5 College 6

Other (specify) 7 I.N.A. 8

10. Occupation: Desk work 1 Field work 2

Field work with physical labour 3

Field work with intellectual 4


11. Family income per month in Rs. Rs. Income per capita in Rs.

12. Religion: Hindu 1 Muslim 2 Sikh 3

Christian 4 Parsi 5

13. Dietary Pattern: Vegetarian Non-Vegetarian

260

14. Likes: __________________________________________________________________

15. Habits: Smoking Drinking Chewing Pan

Tobacco

HISTORY Yes (1) No (0) Duration(in days)

16. Chronic illness:

17. Allergy:

18. Surgery:

19. Communicable diseases

FAMILY HISTORY

20. Type of family: Nuclear No. of persons:

Joint: No. of persons:

Yes (1) No (0)

21. Diseases: Chronic illness:

Hypertension:

Diabetes:

Genetic disorders:

If yes, specify: __________________________________________________

Psychiatric disorder:

Other:

22. History of recent delivery (in case of female): ___________________________________

HISTORY OF PRESENT COMPLAINTS Yes (1) No (0)

23. Pain or burning sensation during or after defaecation

24. Bleeding per rectum during or after defaecation

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25. Associated with Itching or irritation around the Anus

26. A visible crack in the skin around the Anus (Fissure-in-ano)

27. Bright red blood on the outside of the stool or onthe toilet paper

28. Constipated bowels

29. Medication: Yes (1) No (0)

a. Whether received any treatment previously

b. Any surgical interventions made for any disease

CLINICAL EXAMINATION Yes (1) No (0)

General Examination

30. Blood Pressure: TPR:

31. Height

32. Weight

33. Chest : Auscultation: Heart: Lungs:

34. Abdomen:

35. Extremities - Inspection: Clubbing of fingers

Pedal Oedema: Varicose veins:

Local / Peri-anal Examination:

1. Condition of skin around anus:

2. Condition of the fissure :

Acute Chronic

Presence of Sentinel pile : Yes / No

Position of the fissure o clock position:

No. of fissures :60

120

90 30

262

3. Digital examination

Tenderness Present / Absent

Sphincter tone:

Hyper tonic /Normal /Hypo tonic

Any mass palpated in the canal

4. Anoscope/Proctoscopic examination (not in Acute cases)

Treatment:

Group: I

• Triphala churna: 5gm with warm water daily at bed time for 28 days

• A novel method of Anal dilatation for 07 days

• Hot Sitz bath for 28 days Anal dilatation:

A self retaining Foley’s rubber catheter no. 18 is smeared with 2% lignocaine jelly andinserted in the Anal canal up to 4 cm. from the tip and on the first day the bulb is inflated with 5ml of water and gently pull the catheter downward till it sustains maximum resistance and thecatheter is allowed to stay in position for one minute. Then the water is withdrawn from the bulband the catheter is removed from the Anal canal. After removing the catheter the patient is givenhot sitz bath for two minutes. The catheter is sterilized properly and reused in the same patient fornext sittings.

The procedure remains unchanged except in the increase in the volume of the water from5ml to different volumes as indicated below:

Day 1 : 5ml

Day 2 : 7ml

Day 3 : 10ml

Day 4 : 15ml

Day 5 : 20ml

Day 6 : 20ml

263

Day 7 : 20ml

Group: II


• Anal dilatation with Jatyadi Ghrita for 07 days


Anal dilatation:

Take sufficient quantity of Jatyadi Ghritam in a sterile bowl. Initially the little finger (goved)is well smeared with the Ghritam and gently inserted in the Anal canal watching the resistanceproduced by the sphincter. Care should be taken to push the finger always against the non-ulcerwall of the Anal canal and inwards. After the little finger is inserted in to the canal allow to remainthe finger in the canal for one minute. Then the finger is withdrawn slowly and then index finger isinserted following the same principle and wait for two minutes. Then index and middle fingers areinserted together and kept for three minutes in the canal. Care should be taken that the fingersand the anal canal are well lubricated with the Ghritam. After the procedures are completed thepatient is allowed hot sitz bath for three minutes. The same procedure is to be carried out forseven days.

Group: III



• Application of Jatyadi Ghrita (P/R) (without dilatation) for 07 days

Application of Jatyadi Ghrita (P/R)

The patient is first asked to take hot sitz bath then with the help of gloved little finger theJatyadi Ghritam is applied gently in the Anal canal without applying much pressure in the canal.The same procedure is to be carried out for seven days.

Remarks:

Signature of the Investigator

264





(From day one to seventh day and subsequently on 14th, 21st, 28th, 35th &42nd day)



1. Centre: ………………..……….






7. Day of Assessment: 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 14th, 21st, 28th, 35th & 42nd day

CLINICAL ASSESSMENT CHART: (Mention ‘Y’ for Yes, ‘N’ for No)

FOLLOW UP

Symptoms & Signs: Initial First month Second month Third month

Abdominal pain-Day of onset-Intensity-Relief after passageof clots-Nature of pain

-Toda

265

- Bheda- Sula

Low back pain-Day of onset-Intensity-Relief after passageof clots-Nature of pain

-Toda- Bheda- Sula

Pain in lower limbs

Nausea / Vomiting

Constipation

Giddiness

Tenderness on palpation

Breast tenderness

Diarrhea

Headache

Fainting

Drug Compliance Chart: 100% 75-99% 50-74% <50%

1.

2.

3.

Complications if any:

Outcome of Trial:


Completed:

Drop out: Reason: ____________________________

Died: Cause______________________________

Date: Signature of the Investigator

266


MLTI CENTRIC OPEN CLINICAL TRIAL ON THE MANAGEMENT OFFISSURE - IN ANO (PARIKARTIKA)

CASE REPORT FORM IV - A - LABORATORY INVESTIGATIONS

(On Day 1)

(Enter a �in the appropriate box)

1. Centre: ………………..……….




5. Address ................................................................................................................................



Routine: _______________________ Microscopic: ___________________


Routine: _______________________ Microscopic: ___________________

Occult Blood: __________________ Ova/Cyst: ___________________

Blood Examination

9. TLC (Cells/Cmm.): _______________

10. DLC: P _____ (%) L _____ (%) E ______ (%) M _____ (%) B ______(%)

11. ESR (mm / 1st hour.) __________

12. Hb (g/dl) (Cyanmethaemoglobin method) ____________________

13. General Blood Picture for morphology of RBC ______________________

Normocytic Normochromic /Microcytic Hypochromic /Macrocytic Normo/hypochromic

267


14. S. Bilirubin (mg/dl)

15. SGPT (IU/L)

16. SGOT (IU/L)

17. S. Alkaline phosphatase (KA unit)

18. S. proteins (gm/dl)



20. S. Creatinine (mg/dl)

Date: _____________ Signature of investigator _______________________________

268



(On Day 35)

CASE RECORD FORM IV-PERIODICAL OBSERVATION AND ASSESSMENT

FORM IV-B – LABORATORY INVESTIGATIONS


1. Centre: ………………..……….






7. Address: ...............................................................................................................................


9. Hb (g/dl) (Cyanomethaemoglobin method) ____________________


Normocytic Normochromic /Microcytic Hypochromic /Macrocytic Normo/hypochromic

Date: _____________ Signature of investigator _______________________

269



CASE RECORD FORM V-CONSOLIDATED DATA ON PERIODICALOBSERVATIONS


1. Centre: ………………..……….






7. Address: ...............................................................................................................................


Sl Subjective/ objective 0 day/BT 15th day 30th day 45thday/ATParameters Dt. Dt. Dt. Dt.

1. M.C.V. (Fl)

2. Serum iron (ìg/dl)

3. Serum ferritin (ìg/dl)

4. Hb (g/dl) (Cyanomethaemoglobin method)

5. PCV (%)

6. General Blood Picturefor morphology ofRBCNormocyticNormochromic

270

Microcytic Hypochromic

Macrocytic Normo/hypochromic


S. Bilirubin (mg/dl)

SGPT (IU/L)

SGOT (IU/L)

S. Alkaline phosphatase(KA unit)

S. Proteins (gm/dl)


Blood urea (mg/dl)

S.Creatinine(mg/dl)


Improved No change Deteriorated



Status of the patient:

Continuing

Drop out Reason: _____________________________

Died Cause: _______________________________

Date: ______________ Signature of investigator _________________________

271

Drug: Study Code:


COMPARATIVE CLINICAL EVALUATION OF SELECTAYURVEDIC TREATMENT MODALITIES IN THE

MANAGEMENT OF ARSHA


272

Blank

273

I. BACKGROUND

Concept of Arsha as described in Ayurveda is quite wider. ‘Arsha’ includes a variety ofconditions pertaining to Ano-rectal and other parts/organs of the body. Present study includesconditions pertaining to Ano-rectal Arsha. Only Sushruta has described four fold methods oftreatments of Arsha (Su. Ci. 6), which are Bheshaja, Kshara, Agni and Shastra. Bheshaja i.e.Medical/conservative treatment includes various Ayurvedic medicines which decrease intra-abdominal pressure, act as mild laxatives and thus give relief in the particular situation. Some otherOils/like Kashishadi taila when used locally (Lekhana) imparts relief in Arsha. The commonly usedmedicines are – Abhayarishta, Draksharishta, Satsakara churna, Triphala churna, Satpushpadichurna etc. Locally Kashishadi tila and inflammatory conditions Jatyadi taila are prescribed.

In certain other cases Ksarakarma and Ksharasutra are used effectively. Plain threadligation of prolapsible internal haemorrhoids is also a popular method of treating the haemorrhoidson OPD basis (Sharma, 1999). Raktavasecana, Agnikarma and Shastrakarma are some othermethods. However the Shastrakarma needs general/spinal anaesthesia. Bheshaja (Medicine)treatment is the most suitable treatment in the Arsha of:

• Rectal origin

• History of mild/moderate bleeding

• Small, negligible or invisible haemorrhoidal mass

• Associated with diarrhoea/dysentery


COMPARATIVE CLINICAL EVALUATION OF SELECT AYURVEDICTREATMENT MODALITIES IN THE MANAGEMENT OF ARSHA

References

1. Baily and Love – Short practice of surgery, 24th Edition, 2004, Arnold Publication, London

2. Charaka Samhita, Chikitsa Sthana, Arsha Chikitsa, Chapter–15, Vidyotini Hindi Vyakhya by Pt.Kashinath, Choukhamba Orientalia, Varanasi


4. Ambika Dutta Sashtri(1989) Susruta samhita (text with Hindi commentary) Nidana Arshonidana2nd Chapter, Chi. 6th Chapter, VIIth Edition Chaukhamba Sanskrit Series Office, Varanasi.

274

It is safe and easily available method to prescribe medicines and patient’s acceptability isgood. Bheshaja chikitsa can however be mixed with other techniques or therapeutic measures.Piles (haemorrhoids – internal haemorrhoids arise in the upper Anal Canal and lower rectum formthe internal various haemorrhoidal plexus. They enlarge to involve the skin-lined lower Anal Canaland the external haemorrhoidal venous plexus to become visible externally.

Bright red bleeding is common as is prolapse of the piles on defecation, discomfort,mucuous discharge and partial incontinence. The patient is investigated by proctoscopy and tehnby sigmoidoscopy to ensure that no other lesion is responsible for the bleeding. Symptomatic pilesare treated on an out patient basis by injection of sclerosant or by rubber band ligation.Haemorroide ctomy is reserved for more severe cases.

II. OBJECTIVE

Bhesaja, Ksarakarma, Raktavasecana, Agnikarma and Sastrakarma are the measureadopted to treat Arsha Roga (Haemorrhoids) as described in Ayurvedic texts. The present studyis aimed at reducing the effect of some Ayurvedic medicines oral and local upon Gudarsh (Piles)in various groups for comparison. The therapy so planned is non-invasive and may give relief toa patient while keeping him active (at O.P.D. levels).

III. CENTRES:

Identified centres of CCRAS,New Delhi .

IV. SAMPLE SIZE AND METHODS:

Sample Size : 90 patients (30 patients in each group)

Trial Drug/Dosage/Duration

Group I : Kankayan Vati : 500 mg thrice a day

Triphala Churna : 5 gm at bed time

Kaseesadi Taila : 2 ml locally before defecation

Group II : Kravyadi Rasa : 500 mg thrice a day

Triphala Churna : 5 gm at bed time


Group III : Kankayan Vati : 500 mg thrice a day

Kravyadi Rasa : 500 mg thrice a day along with

Abhayarishta : 15 ml thrice a day


275

Diet

Normal diet

Design of the study – Single blind open trial.

Duration of the Study - 21 days drug therapy with a follow up for every 15 days upto 3months


1) Age > 5 years

2) Sex-either-sex

3) Fresh/previously operated

4) Painful/painless

5) Bleeds/does not bleed

6) Ano-rectal Arsha only/pertaining to Ano-rectal

7) Pile mass palpated/seen by P/R exam or proctoscopy

VI. CRITERIA OF EXCLUSION

1) Patients with malignancy

2) Incontinence of stool

3) Corrhosis liver-portal hypertension

4) Tuberculosis/Diabetes/Systemic disease

5) Bleeding diathesis

6) Multiple haemorrhoids/externo-internal haemorrhoids


(i) Discontinuation of treatment during trial

(ii) Development of any complication

(iii) Aggravation of the disease symptoms

(iv) Any side effect of the drug


The full details of screening, history and physical examination of the subjects will berecorded as per case report form I & II. Clinical and physiological assessment in form III and

276

laboratory investigations i.e. Urine Routine & Microscopic, Stool Routine & Microscopic, TLC,DLC, ESR, Hb%, B.T., C.T., P.T., Blood Sugar Fasting &PP, Proctoscopy, Sigmoidoscopy willbe done.


Assessment will be done as per proforma after three months of regular treatment. Howeverthe patients are to be reviewed after every 15 days.

Good Response

Complete disappearance of known symptomatology in absence of any other complicationwith considerable regression in the size of pile mass.

Fair response

50% and above relief in presenting symptomatology of the disease with no/negligiblechange in the size of pile mass.

X. TRIAL MONITORING AND STATISTICAL DATA ANALYSIS

Progress of the study can be mentioned by the clinicians by P/R exam or proctoscopy.Improvement in symptoms can also be assessed and the data analyzed statistically.

XI. ETHICAL REVIEW:

Institutional Ethical Committee (IEC): The proposal will be placed before InstitutionalEthical Committee (IEC) of trial center for getting clearance certificate before the project isinitiated. Patient’s information sheet and informed consent form will be submitted along with projectproposal for approval by IEC.


A consolidated amount of Rs.…… /- per visit.


Short-term training will be provided to the Investigators and Laboratory personnelinvolved in the multi-centric trial at CCRAS Hqrs., New Delhi. The investigators and technicianswill be detailed about the clinical trial conduct and laboratory procedures in order to maintain theuniformity.


The Laboratory Investigations (Pathological/Biochemical, etc.), which are not available atresearch Institutes should be conducted at identified reputed labs /Government Institutes underintimation to this Council following Codal formalities.

277






Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “Comparative Clinical Evaluation of select Ayurvedic TreatmentModalities in the Management of Arsha”.





Relationship ___________________________________


278





Concept of Arsha as described in Ayurveda is quite wider. ‘Arsha’ includes a variety ofconditions pertaining to Ano-rectal and other parts/organs of the body. Present study includesconditions pertaining to Ano-rectal Arsha. Only Sushruta has described four fold methods oftreatments of Arsha (Su. Ci. 6), which are Bheshaja, Kshara, Agni and Shastra. Bheshaja i.e.Medical/conservative treatment includes various Ayurvedic medicines which decrease intra-abdominal pressure, act as mild laxatives and thus give relief in the particular situation. Some otheroils/like Kashishadi taila when used locally (Lekhana) imparts relief in Arsha. The commonly usedmedicines are – Abhayarishta, Draksharishta, Satsakara churna, Triphala churna, Satpushpadichurna etc. Locally Kashishadi tila and inflammatory conditions Jatyadi taila are prescribed.

In certain other cases Ksharakarma and Ksharasutra are used effectively. Plain threadligation of prolapsible internal haemorrhoids is also a popular method of treating the haemorrhoidson OPD basis (Sharma, 1999). Raktavasecana, Agnikarma and Shgstrakarma are some othermethods. However the Shastrakarma needs general/spinal anaesthesia. Bheshaja (Medicine)treatment is the most suitable treatment in the Arsha of:

• Rectal origin

• History of mild/moderate bleeding

• Small, negligible or invisible haemorrhoidal mass

• Associated with diarrhoea/dysentery

It is safe and easily available method to prescribe medicines and patient’s acceptability isgood. Bheshaja chikitsa can however be mixed with other techniques or therapeutic measures.Piles (haemorrhoids – internal haemorrhoids arise in the upper Anal Canal and lower rectum formthe internal various haemorrhoidal plexus. They enlarge to involve the skin-lined lower anal canaland the external haemorrhoidal venous plexus to become visible externally.

Bright red bleeding is common as is prolapse of the piles on defecation, discomfort,mucuous discharge and partial incontinence. The patient is investigated by proctoscopy and tehnby sigmoidoscopy to ensure that no other lesion is responsible for the bleeding. Symptomatic pilesare treated on an out patient basis by injection of sclerosant or by rubber band ligation.Haemorroide ctomy is reserved for more severe cases.

279


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 90 days. During treatment period,you are expected to visit the hospital six times i.e. on 15th, 30th, 45th, 60th, 75th and 90th day forclinical and physiological assessment.





280




1. Name of the patient ....................................................... Age .................. Sex ...................

. Address: ............................................................................................................................................................................................................................................................

2. Centre


4. Group No. First Second

Third Fourth

CRITERIA FOR INCLUSION YES NO

5. Age > 5 years

6. Ano-Rectal Arsha (Haemorrhoids)

7. Arsha seen on P/R proctoscopy

8. Bleed/does not bleed

9. Painful/Painless

10. Fresh/Previously operated

CRITERIA FOR EXCLUSION YES NO

11. Patient with malignancy

12. Incontinence of stool

13. Cirrhosis liver-portal hypertension

14. Tuberculosis/Diabetes/Systemic disease

15. Bleeding diathesis

281

16. Multiple haemorrhoids/externo internal haemorrhoids

17. Cardiac disease/neurological disease


If Sl. No. 5 to 10 is ‘Yes’ and Sl. No. 11 to 17 are ‘No’

Date: _______________ Signature of the Investigator: ____________________

282





2. Address: ..............................................................................................................................

3. Date of Admission Date of Discharge

4. Centre



Third Fourth

7. Educational status: Illiterate Read and write Primary

Middle school High school College

Others (specify) INA

8. Occupation Desk work Field work

Field work with physical labour

Field work with intellectual

Indicate nature of work…………………………….................................

9. Total income of the family (in Rupees)

10. Total family members

11. Income per capita per month (in Rupees)

12. Religion Hindu Mulsim Christian

Parsi Others

283

13. Marital status Married Unmarried Divorcee/ separated

Chief complaints with duration (in months)

Present Absent Duration

14. Pain

15. Swelling

16. Tenderness

17. Itching

18. Indurations

19. Bleeding Mild Moderate

Before defecation With defecation

After defecation

20. Type of pain Pricking Cutting Throbbing

Burning Itching Mixed


21. Onset of disease Operated Non-operated

22. Duration of disease

23. Location of pile mass O’clock position

24. Size of pile mass

25. Sentinel tag/Thrombotic pile

FAMILY HISTORY, IF ANY YES NO

26. Hypertension


28. Piles

284

29. Tuberculosis

30. Others

If yes specify………….......………………………….…………………………………….

PERSONAL HISTORY Yes No

31. Smoking

32. Obesity

33. Non-vegetarian

34. Alcoholic

35. Spices intake

36. Emotional stress

37. Bowel habit

38. Sharirik Prakriti

Vataja Pittaja Kaphaja

Vata Kaphaja Vata Pittaj Pitta Kaphaj

Sannipataj

39. Manas Prakriti

Sattva Rajas Tamas

Sattva-Rajas Sattva-Tamas Raja-Tamas

Sama


40. Built Lean Medium Heavy



285


44. Pulse

45. Respiration


46. Pulse rate

47. Oedema C.V.S.

GASTRO INTESTINAL TRACT Present Absent

48. Hepatomegaly

49. Sleenomegaly

50. Tumour/Lump

51. Portal hypertension

SAMPRAPTI (PATHO GENESIS) OF THE DISEASE ACCORDING AYURVEDICCONCEPT

52. Dosh Vata Pitta Kapha

53. Dushya Rasa Rakta Mamsa

Meda Asthi Majja

Shukra

54. State of disease (Roga kriya kala)

Sanchaya Prakopa Prasar

Sthanasamshraya Vyakti Bheda

Date: _______________ Signature of the Investigator: _________________________

286



CASE REPORT FORM III -PERIODICAL OBSERVATION AND CLINICALASSESSMENT

(On Day 0, 15 days, 30 days, 45 days, 60 days, 70 days and 90 days)



1. Code No. (of clinical trial)_____________________

2. Centre________________________________

3. Sl. no. of the subject ____________________

4. Name __________________________________________Age________ Sex_________

5. Date of Assessment _________________________

Chief complaints with duration (in days) Present Absent Duration

6. Pain

7. Swelling

8. Tenderness

9. Itching

10. Indurations

11. Bleeding Mild Moderate

Before defecation With defecation

After defecation

12. Type of pain Pricking Cutting Throbbing

Burning Itching Mixed

If yes, specify_________________________

Date: _______________ Signature of the Investigator: ___________________

287



CASE REPORT FORM IV- LABORATORY ASSESSMENT

1. Code No. (of clinical trial)_____________________

2. Centre________________________________

3. Sl. no. of the subject ____________________

4. Name __________________________________________Age________ Sex_________

5. Date of Assessment _________________________


Routine Microscopic


Routine Microscopic

Occult Blood Ova/Cyst

Blood

8. TLC (Cells/Cu. mm.) _______________

9. DLC - P _____ (%) L _____ (%) E ______ (%) M _____ (%) B ______(%)

10. ESR (mm / 1st hour.) __________

11. Hb (g/dl) (Cyanomethamoglobin method) ____________________


12. S. Bilirubin

• Total (mg/dl)

• Direct (mg/dl)

288

13. SGPT (IU/L)

14. SGOT (IU/L)

15. S. Alkaline phosphatase (U/L)

16. S. Proteins (Total) (g/dl)

• Albumin (g/dl)

• Globulin (g/dl)



18. S.Creatinine (mg/dl)

19. Blood Sugar

• Fasting

• Post prondial

20. S. Cholesterol

Special Tests

(i) Proctoscopy

(ii) Sigmoidoscopy

Date: _____________ Signature of investigator _________________________

289



CASE REPORT FORM I – SCREENING OF THE CASES

1. Name of the patient…………………………....…….. Age …………….. Sex ……...........

2. Centre


4. Group No.

INITIAL During Treatment

15 Days 30 Days 45 days 60 days 70 days 90 days

CLINICAL PARAMETERS

Pain

Swelling

Tenderness

Itching

Indurations

Bleeding

LAB INVESTIGATIONS

Stool for occult blood

Note: Severity of the symptoms may be graded as I, II and III grades as per positively inincreasing order (mild 1, moderate 2 and severe 3)

* To be done at the beginning and at the end of the study.

290

Blank

291

Drug: Study Code:


COMPARATIVE CLINICAL EVALUATION OFKSHARASUTRA VIS-À-VIS APPLICATION OF KSHARA

VATI IN THE MANAGEMENT OF BHAGANDARA(FISTULA-IN-ANO)


292

Blank

293

I. BACKGROUND

Bhagandara1 (Fistula in ano), Arsha (haemorrhoids) and Gudavidara (Parikartika) are someano rectal torturesome diseases. Among these, Bhagandara is one of the most painful diseases. Itis a disease of ano rectum which is characterized in humans by single or multiple sinuses withpurulent discharge. It is an obnoxious condition.

This is a field where modern surgery could not help much as extensive excision of thefistulous tract result into a wide open wound with slow healing rate. Chances of wound infection,non-healing and recurrences are high. Application of Ksharasutra in the management of fistula-in-ano showed encouraging results (Deshpande et al 1989). The patients can abstain frompsychological trauma and extensive surgery.

Patients can undergo treatment without paralyzing their routine work.

Kshara Vati is also found to help in such cases. Thus it is important to evaluate the resultafter a comparative study.

II. AIMS AND OBJECTIVE

Medical management of diseases in Ayurveda is quite popular. However, there are diseaseswhich can be treated by para-surgical methods in better way. Management of Bhagandara byKsharasutra is one such example. Thus the present study is proposed with a view to:

1. Study the disease pattern of Bhagandara (Fistula in ano)

2. To evaluate the effect of Ksharasutra application in the management of Bhagandara(Fistula in ano)

3. To compare it with the effect of Kshara Vati (applied 7 times in 21 days) in themanagement of Bhagandara (Fistula in ano)

COMPARATIVE CLINICAL EVALUATION OF KSHARASUTRA VIS-À-VISAPPLICATION OF KSHARA VATI IN THE MANAGEMENT OF

BHAGANDARA (FISTULA-IN-ANO)

References

1. Sushruta Nindan 4th cheptar.

294

III. SAMPLE SIZE AND METHODS

Sample Size : 60 cases

No of Groups : 2 (30 patients in each group) (Patients to be randomlyallocated to different treatment groups)

Type of Study : Single blind

Level of Study : O.P.D.

Period of Study : 21 days in Kshara Vati

In Ksharasutra group according to disease

Dose Schedule

(i) Ksharasutra application depends upon the severity and depth of fistula.

(ii) Kshara Vati will be applied seven times at the interval of every two days.

Note: Renewal of Ksharasutra will be decided by the research workers lookingafter the problem.

Diet

Normal diet

IV. CRITERIA OF INCLUSION

1) Age preferably above 8 to 10 years

2) Sex-either-sex

3) Fresh/previously operated

4) Painful/painless

5) Discharging/non-discharging

6) Purulent/non-purulent

7) Tender/non-tender

8) All cases of fistula in ano

V. CRITERIA OF EXCLUSION

1) Patients with malignancy

2) Incontinence of stool/stricture of anus

3) Tuberculosis/Diabetes/Systemic disease/infections

295

4) Bleeding diathesis

5) Fistula connected with other organs like urethra vagina etc.

VI. CRITERIA FOR ASSESSMENT

Assessment will be done as per proforma after 21 days of regular treatment in grouptreated with Kshara Vati. However in case of Ksharasutra application it depends upon the diseaseand physicians perception.

VII. CRITERIA FOR ASSESSMENT OF RESULTS

1. Good Response:

Complete disappearance of known symptomatology

• absence of any other complication

• Normal healing of the wound

2. Fair response:

50% and above relief in presenting symptomatology of the disease

• Absence of complications

• Healing of the wound more than 75%

3. Poor response:

25% to 50% relief in symptomatology + some improvement in the wound

4. No response

No relief in symptomatology or otherwise

VIII. CRITERIA FOR WITHDRAWAL

(i) Discontinuation of treatment during trial

(ii) Development of any complication

(iii) Aggravation of the disease symptoms

(iv) Any toxicity/local reaction of Sutra/Vati


Data of clinical symptoms, physiological parameters and laboratory parameters will betabulated and analyzed by using appropriate statistical methods. The data of each case will haveto be communicated on completion of trial therapy to the Statistical Officer of CCRAS through e-mail for analysis

296

X. TRIAL MONITORING AND DATA ANALYSES

The progress of the trial will be monitored through field visits by monitoring unit ofCCRAS. Data analysis will be undertaken at the Monitoring Unit of CCRAS.

XI. ETHICAL REVIEW:

Ethical Committee (IEC): The proposal will be placed before Ethical Committee(IEC) of trial center for getting clearance certificate before the project is initiated.Patient’s information sheet and informed consent form will be submitted along withproject proposal for approval by EC. Both will be maintained in duplicate with one copygiven to the patient at the time of entry to the trial.


A consolidated amount of Rs.……. /- per visit i.e., on the 1st day of recruitment afterscreening and at the end of 7th, 14th, 21st and 30th day of months. (5 times)


Short-term two-day training will be provided to the Investigators and Laboratorypersonnel involved in the multi-centric trial at CCRAS Hqrs., New Delhi. The investigators andtechnicians will be detailed about the clinical trial conduct and laboratory procedures in order tomaintain the uniformity.


Microscopic

Urine

Routine

Microscopic

Stool Cyst

Routine

Ova

Stool: - For Occult Blood

Sputum: - A.F.B. (To exclude Koch’s if required)

297

Fasting

Blood Sugar

PP

Blood: - TLC, DLC, ESR, Hb%, B.T., C.T., P.T.

X-rays: - Barium enema (as required)

- Fistulo-graphy

Special test: - Proctoscopy

- Sigmoidoscopy

298








Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “Comparative clinical evaluation of ksharasutra vis-à-vis applicationof kshara vati in the management of bhagandara (fistula-in-ano)”.





Relationship ___________________________________


299






Bhagandara (Fistula in ano), Arsha (haemorrhoids) and Gudavidara (Parikartika) are someano rectal torturesome diseases. Among these, Bhagandara is one of the most painful diseases. Itis a disease of ano rectum which is characterized in humans by single or multiple sinuses withpurulent discharge. It is an obnoxious condition.

This is a field where modern surgery could not help much as extensive excision of thefistulous tract result into a wide open wound with slow healing rate. Chances of wound infection,non-healing and recurrences are high. Application of Ksharasutra in the management of fistula-in-ano showed encouraging results (Deshpande et al 1989). The patients can abstain frompsychological trauma and extensive surgery.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 21 days. During treatment period,you are expected to visit the hospital three times i.e. on 0, 8th, 15th and 22nd day for clinical andphysiological assessment.





300




2. Address: ..............................................................................................................................

3. Centre



Third Fourth

CRITERIA FOR SELECTION YES NO

1. Age above 8 – 10 years

2. Either sex

3. Fresh/Previously operated

4. Painful/Painless

5. Discharging/Non-discharging

6. Purulent/Non-purulent

7. Tender/Non-tender

8. All cases of fistula in ano

CRITERIA FOR EXCLUSION YES NO

9. Patient with malignancy

10. Incontinence of stool/stricture of anus

11. Tuberculosis/Diabetes/Systemic disease/Infections

12. Bleeding diathesis

301

13. Fistula connected with other organs like Urethra vagina etc.



Date: _______________ Signature of the investigator: ___________________

302



BHAGANDARA (FISTULA IN ANO)



2. Address: ..............................................................................................................................

3. Date of Admission Date Discharge

4. Centre



Third Fourth








Total iincome of the family (in Rupees)

Total family members

9. Income per capita per month (in Rupees)

10. Religion Hindu Mulsim Christian

Parsi Others

303

11. Marital status Married Unmarried Divorcee/ separated



12. Pain

13. Burning

14. Swelling

15. Tenderness

16. Itching

17. Indurations


18. Onset of disease Acute Insidious

19. Duration of disease (in months)

20. Factors aggravating the disease/chief complaints………….....……………………………...

......…………………………………………………………………………………………

21. Factors relieving main complaints…………………………………………………………...

..……………………………………………………………………………………………

22. History of past illness, having relation with present illness

Yes No

If yes, specify…………………………………………………………………………

Treatment given so far: Modern Ayurvedic Any other

VARIOUS SURGERY DONE YES NO

23. Open + Drainage

24. Drainage + Saucerization

304

25. Excision

26. Saucerization + Wiring

27. Excision + Grafting

No. of times surgery done: Once Twice more than twice

Date of last surgery

FAMILY HISTORY IF ANY YES NO

28. Hypertension


30. Ano Rectal disease

31. Tuberculosis

32. Others

If yes specify…………………………….......……….…………………………………….

32. Sharirik Prakriti

Vataja Pittaja Kaphaja

Vata-Kaphaja Vata-Pittaj Pitta-Kaphaj

Sannipataj

33. Manas Prakriti

Sattva Rajas Tamas

Sattva Rajas Sattva Tamas Rajas Tamas

Sama



35. Gait Normal Abnormal

305




39. Pulse

40. Respiration

Present Absent

41. Anaemia

42. Jaundice

43. Lymphadenopathy


Normal Abnormal

44. C.V.S. (With Chest)


45. C.N.S








306

SAMPRAPTI (PATHO GENESIS) OF THE DISEASE ACCORDING AYURVEDICCONCEPT

49. Dosha Vata Pitta Kapha

50. Dushya Rasa Rakta Mamsa

Meda Asthi Majja

Shukra

51. State of disease (Roga kriya kala)


Sthanasamshraya Vyakti Bheda

LOCAL EXAMINATION

52. Inspection

1). Condition of skin near fistula YES NO

Normal

Inflamed

Indurated

External piles/tags

Discolouration of skin

2). Opening

No. Position (Clockwise) Distance from anal verge in Cm.

3). Digital Examination

Fissure Yes No

Thrombotic piles Yes No

Sphincteric tone Normal

Hypertonic

307

Hypotonic

Prostate Normal Enlarged

4). Type of discharge

(i) Blood (ii) Pus (iii) Faecal material (iv) Urine (v) Gas

5). Probing

Location of Fistula Towards

Depth of Fistula Cms.

Character of Fistula

(i) Blind ext. (ii) Blind int.

(iii) Complete (iv) Bilateral

(v) Radial (vi) Curved

(vii) Horse shoe (viii) Straight

6). Proctoscopy YES NO

1. Presence of pile

2. Inflammation

3. Location of int. opening

7). Sigmoidoscopy

1. Done 2. Not done

If done then………………………………………………………………………….

Yes No

A. Ulceration

B. Bleeding

C. Mucous

308

8). Biopsy

1. Done 2. Not done

CLASSIFICATION OF FISTULA

53. Modern view

1. Low cutaneous

2. Sub. Mucous

3. Low anal

4. High anal

5. Ano rectal

6. Pelvi rectal

54. Ayurvedic view

1. Shataponak (Vataja)

2. Ushragreeva (Pittaja)

3. Parisravi (Kaphaja)

4. Shambukartava (Sannipataja)

5. Unmargi (Agantuja)

Provisional Diagnosis

Final Diagnosis

Principal Drug Therapy

Date: ………………….. Signature of the Investigator: ………………………..

309





1. Centre………………………………………………………………………………………


3. Patient No.

4. Group No.

INITIAL Days after starting therapy

7th day 14th day 21st day 30th day

5. Pus-discharge

6. Induration

7. Inflammation

8. Pain

9. Burning sensation/itching

10. Bleeding

ASSESSMENT OF UNIT CUTTING TIME OF FISTULOUS TRACT

UNIT CUTTING TIME TOTAL NO. OF DAYS

INITIAL LENGTH IN CMS.

(OF FISTULA)

Date: ………………………... Signature of the Investigator: ………………

310




CASE REPORT FORM IV– INVESTIGATION

1. Centre………………………………………………………………………………………


3. Patient No.

4. Group No.

Investigation Time of after 7 days after 14 days after 21days after monthAdmission

Microscopic

5. Urine

Routine

6. Urine Glucose

Microscopic

7. Stool Cyst

Routine

Ova

8. Stool: for Occult blood

9. Haematology: TLC

DLC

ESR……………(1 Hr.)…………..mm. (2 Hr.)…………..mm.

311

10. Biochemistry

Fasting

11. Blood Sugar

PP

Bariumenema (if required)

Fistulogram

Proctoscopy

Sigmoidoscopy (if required)

Date: ………………………... Signature of the Investigator: ………………………..

312

Blank

NERVOUS SYSTEM

SEC

TIO

N - V

314

Blank

315

Treatment modalities : Study Code:


DOUBLE BLIND CLINICAL TRIAL OF AYURVEDICTREATMENT IN THE MANAGEMENT OF

PAKSHAGHATA


316

Blank

317

I. BACKGROUND

Paksaghata (hemiplegia) is a major disabling disease of mankind. The terms Paksaghata,Parsavadha and Ekangaroga are synonyms of the same disease and are used in classicaltreatises in various contexts. Caraka has classified it as Nanatmaja vata vyadhi caused due tovitiation of Vata dosa and considered it as a Maharoga from the point of prognosis – difficult tocure. According to the concept, the disease affects the Madhyama roga marga and disrupting thefunctions of Sira, Snayu, Kandara etc. According to modern terminology, hemiplegia is thesequelae of pathological events which take place in the central nervous system, may be due todifferent factors such as cerebro-vascular accidents neoplasm, infections etc. where in paralysiswill be common symptom. Ayurveda has a definite pattern of treatment for such conditions. Theline of treatment includes Snehana, Svedana and Panchakarma therapy. The Snehana andSvedana therapy mentioned in the classics are used as preparatory mearues for Sodhana therapy.(Caraka Samhita Chikitsa 28-100, Susrut Chikitsa 5-19). This Council has taken up thisproblem for research and different methods of therapy used in clinical practice are taken up forintensive evaluation of their efficacy of samana therapy alongwith Panchakarma therapy. A seriesof clinical studies to evaluate the effect of herbo-mineral preparation and application of Sastikasalipindasveda with Brihat Masa Taila alongwith Panchakarma therapy has shown that thesetherapies are giving significant results and found effective in relieving hypertenic (stiffness) ofmuscles and to improve the functional ability of the affected limb (P.K.N. Namboodiri et al,2000, Management of Hemiplegia by Panchakarma & Samana therapy CCRAS). The objectiveof present study is to evaluate the effect of samana &panchakarma therapies with and withoutinternal medication in the management of Paksaghata1.

II. OBJECTIVES

To assess the efficacy of Ayurvedic treatment in the management of Pakshaghata.


DOUBLE BLIND CLINICAL TRIAL OF AYURVEDIC TREATMENT IN THEMANAGEMENT OF PAKSHAGHATA

References

1. Charak Chikitsa 28 Ch. (Vata Vyadhi Chikitsa)

318

III. CENTRE

CCRAS identified Centers.


Sample Size : 100 patients (50 in each in group, two groups)

Treatment

A. Sodhan Chikitsa

1. Snehapana - Murchita tila taila (maximum 7 days)

2. Svedana - Vaspa Sveda (3 days)

3. Virecana - Eranda Taila (1 day)

4. Samsarjana - 7 days

5. Abhyanga - Brihat masa Taila (7 days)

6. Yogabasti (8 days) (a) Anuvasana – Morchitataila (240ml) [1st, 3rd, 5th,7th, 8th] (Oil Enema –Dose 240ml)

(b) Asthapana – [2nd, 4th, 6th]

(Decoction Enema – Dose 960ml)

Erandamula Kvatha (480 ml.)

Morchitataila (240ml)

Honey – 180 ml

Satahva – 24 gm

Saindhava – 12 gm

** One Day Rest

7. Nasya Kshirabala taila - 3 times (Potency) (7 days)

** One Day Rest

B. Samana therapy

Internal _ Ekangavirarasa (250 mg twice daily)/ Placebo (250 mg.) BD.

Externally – 1. Morchitataila (50ml) (Abhayanga)

2. Sastikasali pinda Sveda – 14 days

319

Design of Study: Randomized double blind placebo controlled study.

1. All the patients will be provided with the Sodhana therapy for 35 days.

2. After completion of Sodhana therapy patients will be devided into two groups. One groupwill receive trial drug in the dose of 250 mg. twice daily for 30 days along withAbhyanga for 30 days and Sastikasasli pinda sveda for 14 days. The other group willreceive placebo in the dose of 250 mg. twice daily for 30 days along with Abhyanga for30 days and Sastikasasli pinda sveda – for 14 days. Oral drug as well as Abhyangaand Sastikasasli pinda sveda will run simultaneously.

Period of Study: Six months of each case. Total duration will be two and half years to completethe study.

Follow Up: One follow up will be carried out at the end of 6th month.


1. Age: More than 20 years and less than 70 years.

2. Duration of illness more than 6 months but less one year.

3. Patients of stable one time stroke with hemiparesis or hemiplegia with or without facialparalysis.

4. Patients with non-progressive neurological disease causing Para paresis (plegia) such as

- Compressive mydopathy (operated)

- Non-compressive (post-viral, denyclinating, post traumatic, vascular)

5. Motor deficit should be 3/5 or less (MRC Grade).

6. Spasticity of a scale of 3 or more (Ashwarth Scale)

7. Medically stable

8. Fully conscious and oriented

9. Normal Higher mental functions


1. Age less 20 and more than 70 years.

2. Progressive Neurological diseases.

3. Pregnancy & lactation.

4. Insulin dependent diabetis mellitus (IDDM)

320

5. Impaired sensorium

6. Recurrent strokes.

7. History of Renal and liver diseases

8. Cases undergoing treatment for any other serious illness.


A patient may be withdrawn from the study on account of the following.

1. Recurrent attacks of strokes.

2. Development of any major ailments, side effects necessitating institution of new modalitiesof treatment.

3. Worsening of symptoms.

4. Patient failure to report for follow-up or irregular medication.


The full details of history and physical examination of the patients will be recorded as perthe proforma (Forms I & II). Clinical assessment will be done before the therapy, at the end of5th week, end of 9th week, end of 6th month (Form III). The lab investigations will be recordedbefore therapy, end of 5th week, end of 9th week and at the end of follow up (6th month)(Form IV).

IX. CLINICAL ASSESSMENT:

MOTOR PARALYSIS

a). Clinical muscle strength testing – MRC Grading:

0. - Nil

1. - Flicker of movement.

2. - Movement with gravity eliminated.

3. - Movement against gravity.

4. - Movement against minimal resistance

5. - Movement against maximum resistance.

b). ADL (Activities of Daily Living) Score

c). Dynamometers – for measuring isometric strength.

321

Spasticity:

A. Clinical

a. -Ashworth Scale Score:

0. - No increase in tone

1. - Slight increase producing a catch when a joint is moved in flexion or extension.

2. - More marked increase in tone, but joint easily flexed

3. - Considerable increase and passive movements difficult.

4. - Affected part rigid in flexion or extension.

b. -Spasm Score:

0. - No spasms

1. - Mild spasms induced by stimulus

2. - Spasms occurring less than 1 per hour

3. - Spasms occurring more than 1 per hour

4. - Spasms occurring more than 10 per hour

c. - Reflex Score:

0 - Absent

1 - Flicker/elicitable only on reinforcement

2 - Diminished knee/normal other DTR (deep tendon reflexes)

3 - Normal knee/hyperreflexia of other DTR

4 - Clonus – illsustained

5 - Sustained clonus

B. Biomechanical Techniques:

Biomechanical techniques evaluate changes in the phasic and tonic reflex activity of themuscles across a joint.

- Wartenberg’s pendulum or the “drop” test.

- With an electrogoniometer to record the changes in the knee joint angle.

- Relaxation index.

322




The progress of the trail will be monitored by field visits by Monitoring unit of CCRAS.Data analysis will be undertaken at the Monitoring Unit of CCRAS

XII. ETHICAL REVIEW

A. Ethical Committee (IEC): The proposal will be placed before Ethical Committee (IEC)of trial center for getting clearance certificate before the project is initiated. Patient’sinformation sheet and informed consent form will be submitted along with project proposalfor approval by EC. Both will be maintained in duplicate with one copy given to thepatient at the time of entry to the trial.

B. Data and Safety Monitoring Board: A Data and safety monitoring board (DSMB) atHqrs. will carefully monitor the data and side effects during the period of study and put ina place where by prompt reporting of adverse events occur. The data will be reviewed asevery 20 participants entered the study and administered the trial drugs. The research teamwill report immediately to the PI and Data Monitoring Board if, any life threateningconditions whether they are perceived to be study related or not. The Board decideswhether the adverse effects warrant discontinuation of the study protocol. Protocols will bewritten and approved for the treatment of study related adverse events.

XIII. TRAVELLING EXPENSES

A consolidated amount of Rs……../- per visit will be paid to the subject.




The Laboratory Investigations (Pathological / Biochemical, Radiological / Sonography etc.)which are not available at research Institutes will be referred to any reputed/Government Institutesunder intimation to this Council following codal formalities.

323


DOUBLE BLIND CLINICAL TRIAL OF AYURVEDIC TREATMENT IN THEMANAGEMENT OF PAKSHAGHAT





Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the, “Double blind clinical trial of Ayurvedic treatment in the management of pakshaghat”.





Relationship ___________________________________


324


DOUBLE BLIND CLINICAL TRIAL OF AYURVEDIC TREATMENT IN THEMANAGEMENT OF PAKSHAGHAT



Pakshaghata (hemiplegia) is a major disabling disease of mankind. The terms Pakshaghata,Parsavadha and Ekangaroga are synonyms of the same disease and are used in classical treatisesin various contexts. Caraka has classified it as Nanatmaja vyadhi caused due to vitiation of Vatadosa and considered it as a Maharoga from the point of prognosis – difficult to cure. Accordingto the concept, the disease affects the Madhyama roga marga and disrupting the functions of Sira,Snayu, Kandara etc.

According to modern terminology, hemiplegia is the sequelae of pathological events whichtake place in the central nervous system, may be due to different factors such as cerebro-vascularaccidents neoplasm, infections etc. where in paralysis will be common symptom. Ayurveda has adefinite pattern of treatment for such conditions. The line of treatment includes Snehana, Svedanaand Panchakarma therapy. The Snehana and Svedana therapy mentioned in the classics are usedas preparatory mearues for Sodhana therapy. (Caraka Samhita Chikitsa 28-100, Susrut Chikitsa5-19). This Council has taken up this problem for research and different methods of therapy usedin clinical practice are taken up for intensive evaluation of their efficacy of samana therapyalongwith Panchakarma therapy. A series of clinical studies to evaluate the effect of herbo-mineralpreparation and application of Sastikasali pindasveda with Brhat Masa Taila alongwithPanchakarma therapy has shown that these therapies are giving significant results and foundeffective in relieving hypertenic (stiffness) of muscles and to improve the functional ability of theaffected limb (P.K.N. Namboodiri et al, 2000, Management of Hemiplegia by Panchakarma &Samana therapy Snamaa and Panchakarma, CCRAS). The objective of present study is toevaluate the effect of samana & panchakarma therapies with and without internal medication in themanagement of Paksaghata.

However, considering the eco- climatic changes traces of certain unwanted substances maylead to untoward effects. Thus this project is undertaken to assess the clinical safety in subjectsreceiving Ayurvedic preparations.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 1 month to complete. During thisperiod, you are expected to visit the hospital 3 times (0, 15 and 30 days) for clinical, biochemicaland physiological assessment.

325

Before you start treatment, during the first visit to the clinic, you will undergo acomplete physical examination, required objective tests and laboratory investigations willalso be done. If you are found eligible, you would be put on treatment for 1 month.

At each visit, you will be supplied with sufficient quantities of drugs to last untilyour next visit. If any adverse reactions like skin allergy, nausea, vomiting andpalpitation/tremor etc., noticed during the treatment period, this should be noticed to the

Date: ______________ Principle Investigator:____________________________________


326


DOUBLE BLIND CLINICAL TRIAL OF AYURVEDIC TREATMENT IN THEMANAGEMENT OF PAKSHAGHATA (HEMIPLEGIA)


BEFORE TREATMENT


1. Centre: ………………..……….





6. Address ……………………………………..…………..........……………………………

CRITERIA OF INCLUSION Yes (1) No (0)

1. Age: More than 20 years and less than 70 years

2. Duration of illness more than 6 months, but less one year

3. Patients of stable one time stroke with Hemiparesis or hemiplegia with or With out Facial Paralysis.

4. Patients with Non Progressive Neurological diseases

5. Motor deficit –3/5 or less[MRC Grade]

6. Spacticity of a scale of 3 or more (Ashworth scale)

7. Medically Stable, fully conscious & oriented

8. Normal Higher Mental Functions


9. Age less than 20 years and more than 70 years

327

10. Progressive Neurological diseases

11. Pregnancy & lactation

12. IDDM

13. Impaired Sensorium

14. Recurrent strokes

15. History of Renal & Liver Diseases




Dated:____________ Signature of the Doctor _________________________

328



CASE REPORT FORM II – HISTORY PROFORMA

1. Centre : ........................................


3. Sr. No. of the Subject : _______________________


5. Address: ..............................................................................................................................









9. Family income per month in Rs.

10. Total Family members :


Present (1) Absent (0) Duration(in months)

11. Paralysis/Weakness of upper limb

12. Paralysis/Weakness of lower limb

329

13. Difficulty for locomotion

14. Rigidity

15. Flacidity

16. Spasm

17. Numbness

18. Head ache

19. Difficulty in speech

20. Pain in either half of the body

21. Incontinence/retention of urine

22. Incontinence/retention of Motion

23. Facial Palsy

24. 26. Other complaints, if any (Specify) ______________________________

25. History of serious illness in the past (if any):___________________________

Personal History

26. Diet: Veg 1 Non-veg 2

27. Bowel habits Regular 1 Irregular 2

Addiction

28. Smoking No 1 Yes 2

If yes specify: (a) Quantity (packs per day) _______________

(b) Total Duration in year’s ______________

29. Tobacco No 1 Yes 2

If yes specify: (a) Quantity per day_________


330

30. Alcohol No 1 Yes 2

If yes specify: (a) Quantity per week (ml)_________


31. Any other(specify)________________

Family History No (0) Yes (1)

32. Hemiplegia

33. Hypertention

34. Cardio vascular disease

35. Other, specify____________________________________________________

36. Prakriti: Vata 1 Pitta 2 Kapha 3

Vata-Kaphaj 4 Vata-Pittaja 5 Pittaja-Kaphaja 6

Sannipataja 7

37. Physical Examination

38. Built Lean 1 Medium 2 Heavy 3

39. Gait Normal 1 Abnormal 2

40. Height (cm) ________________________

41. Weight (kg) ________________________

42. Pulse (per min) ________________________

43. Blood Pressure Systolic(mm Hg) ___________

44. Blood Pressure Diastolic (mm Hg) ___________

45. Respiration rate( per min) ______________

46. Body Temperature ______________

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47. CNS

If abnormal details_____________________________________________



49. CVS






Dated: ________________ Signature of the Investigator_________________

332




(0th, 5th, 9th Weeks and 6th Month)

1. Centre : ........................................




5. Address: ..............................................................................................................................

6. Date of Birth Age (in years)


8. Stage of Assessment: Initial 0 3rd Week 1

11th Week 2 6th Month 3

Clinical Symptoms Absent(0) Present(1)

9. Paralysis/Weakness of upper limb

10. Paralysis/Weakness of lower limb


11. Improvement in locomotion 0____________________________________10

12. Numbness(VAS) 0____________________________________10

13. Improvement in speech 0____________________________________10

14. Incontinence / retention of urine 0____________________________________10

15. Incontinence / retention of Motion 0____________________________________10

16. Facial Palsy 0____________________________________10

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OBJECTIVE PARAMETERS

MOTOR PARALYSIS

17. Clinical muscle strength testing – MRC Grading:

0. - Nil

1. - Flicker of movement.

2. - Movement with gravity eliminated.

3. - Movement against gravity.

4. - Movement against minimal resistance

5. - Movement against maximum resistance.

18. ADL (Activities of Daily Living) Score

19. Dynamometers – for measuring isometric strength.

20. Spasticity

CLINICAL PARAMETERS

21. Ashworth Scale Score:

0 - No increase in tone

1 - Slight increase producing a catch when a joint is moved in flexion or extension.

2 - More marked increase in tone, but joint easily flexed

3 - Considerable increase and passive movements difficult.

4 - Affected part rigid in flexion or extension.

22. Spasm Score:

0 - No spasms

1 - Mild spasms induced by stimulus

2 - Spasms occurring less than 1 per hour

3 - Spasms occurring more than 1 per hour

4 - Spasms occurring more than 10 per hour

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23. Reflex Score:

0 - Absent

1 - Flicker/elicitable only on reinforcement

2 - Diminished knee/normal other DTR (deep tendon reflexes)

3 - Normal knee/hyperreflexia of other DTR

4 - Clonus – illsustained

5 - Sustained clonus

BIOMECHANICAL TECHNIQUES

(Biomechanical techniques evaluate changes in the phasic and tonic reflex activity of the musclesacross a joint.)

24. Wartenberg’s pendulum or the “drop” test

25. With an electrogoniometer to record the changes in the knee joint angle.

26. Relaxation index.

27. Overall clinical assessment by the investigator:

Improved 1 No change 2 Deteriorated 3



Deteriorated 4


Continuing 1

Drop out 2 Reason: _____________________________

Died 3 Cause: _______________________________


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(0th, 5th, 9th week and 6th month)

1. Centre : ........................................




5. Address: ..............................................................................................................................



8. Stage of Assessment: Initial 0 3rd Week 1

11th Week 2 6th Month 3

Urine Examination

A. Routine:

9. pH _______

10. Specific gravity_________


11. Sugar

12. Albumin

13. Bile Salt

14. Bile pigment

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B. Microscopic ______________________________

Blood Examination

15. Hb (g/dl) _______________

16. ESR (1st hour)(mm) _______________

17. TC (Cells/Cmm.) _______________

18. DC: P(%)_____ L(%) _____ E(%)_____ M (%)_____ B(%)_____

19. PCV (%) _______________

20. Blood Sugar – PP(mg./dl)_______________

21. Cholesterol (mg./dl) _______________

22. HDL (mg./dl) _______________

23. LDL (mg./dl) _______________

24. S. Triglycerides (mg./dl) _______________

25. B. Urea (mg./dl) _______________


27. Uric acid (mg./dl) _______________

28. Total proteins (gm./dl) _______________

29. Albumin(gm./dl) _______________

30. Globulin(gm./dl) _______________

31. A/G Ratio _______________

32. SGOT _______________

33. SGPT _______________

34. Total Bilirubin _______________

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Serum Electrolytes

35. Na+ ______________________

36. K+ _______________________

37. Cl- ______________________

38. X-ray Chest: [0 Month only] ___________________________________

39. ECG [0 Month & 6 month] ____________________________________

40. CT Scan [0 Month only] ____________________________________


338

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Drug : Study Code:


ASSESSMENT OF THERAPEUTIC EFFICACY OFAYUSH-M NASAL DROPS AND AYUSH-M CAPSULE IN

THE MANAGEMENT OF MIGRAINE WITH OUTAURA (ARDHAVA BHEDAKA)


340

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341

I. BACKGROUND

Migraine1 (Ardhava Bhedaka) is as old as civilization, occupying 16% among clinicalclassification of headaches, has become a challenging problem to the present day physician1&2. Itis a paroxysmal disorder characterized in its fully developed form by visual and/or sensoryphenomena in an aura associated with or followed by unilateral headache and vomiting. While thisdefinition is satisfactory of ‘Classical’ Migraine, there are many patients who never experience anaura and in whom the headache is always bilateral; the single most characteristic and constantfeature is that migraine is a paroxysmal disorder, i.e., the headaches occur in attacks, separated byintervals of freedom. It is described as a separate clinical entity in the classics of Caraka andSusruta while Vagbhata included this condition in the classification of Vatajashiroroga. A clinicalstudy conducted on 20 cases migraine to evaluate the effect of Nasya Karma with fresh leaf juiceextracted from Acalypha indica Linn. (Haritamanjari,) along with internal medication ofPanchagavya ghrta (Astanga Hradya, Uttara Tantra 7/18) revealed significant clinicalimprovement.

II. OBJECTIVE

To evaluate the therapeutic efficacy of Ayush-M coded nasal drops and Ayush-M capsulein the management of Migraine without aura.


ASSESSMENT OF THERAPEUTIC EFFICACY OF AYUSH-M NASAL DROPSAND AYUSH-M CAPSULE IN THE MANAGEMENT OF MIGRAINE WITH

OUT AURA (ARDHAVA BHEDAKA)

References

1. Peter J Goadsby et al, Diagnosis and management of migraine, Selections from BMJ Vol.12 July,1996 pp 456-460.

2. Classification Committee of the International Headache Society. Classification and diagnosticcriteria for headache disorders, cranial neuralgias and facial pain, Cephalagia 1988 (suppl.7): 1-96.

3. Srikanth N. et al, Clinical study on the role of Nasyakarma and Ghritapana in the managementof Arddhavabhedaka vis-à-vis Migranous headaches, Aryavaidyan Vol.XIX, No.3, Fe-Apr.2001: 166-171.

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III. CENTRE

Central Research Institute (Ay.), New Delhi



Design of the study – Open trial

Treatment

a. Snehana: Local application of Til oil around nose followed by local mridu swedana(mildfomentation) as poorva karma

b. Ayush-M Nasal drops {containing equal parts of Acalypha indica Linn. (Haritamanjari,)and Glycyrrhiza glabra (Yasti madhu) – 3-drops in each nostril after poorva karma for7 days.

c. Ayush-M (Glycyrrhiza glabra (Yasti madhu)- Two capsules (500 mg) twice a day withwater for two months

Duration of the study- Two months drug therapy with a follow up for one month without drug.

Period of Study: Three months for each case. Total duration will be one year to complete thetrial.

Follow – Up: One follow-up will be carried out after one month of the completion oftreatment.


1. Age between 20 years and 60 years

2. Both the sex

3. Patient with five or more attacks of Migraine(headache) without Aura lasting for 4-72hours presenting with a) at least two of the features viz. i) unilateral, ii) Pulsating, iii)Moderate to severe, iv) Aggravated by movement and b)at least one of the features viz.i) Nausea, ii) Photophobia, iii) Phonophobia (Classification Committee of the InternationalHeadache Society. Classification and diagnostic criteria for headache disorders, cranialneuralgias and facial pain, Cephalagia 1988 (suppl.7): 1-96..}


1. Age below 20 and above 60 years

2. Less than five attacks of Migraine without Aura.

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3. Clinically diagnosed cases of

a.. Tension headache

b. Cluster headache.

c. Idiopathic stabbing headache

d. Exertional headache.

e. Headache due to systemic infection.

f. Drug induced headache

4. Organic brain lesions

5. Systemic disorders

6. Person undergoing treatment for any other serious illness


During the course of the trial treatment, if any serious condition develops/ symptomsaggravates, which requires urgent treatment, such subjects may be withdrawn from the trial andmanaged by the Principal Investigator accordingly.


The full details of history and physical examination of the patients will be recorded as perthe Performa (Forms I & II). Clinical assessment will be done before drug administration, at theend of 1st month, 2nd month during treatment and at the end of 3rd month during follow up (FormIII). Required laboratory investigations will be carried out to exclude cases as specified in thecriteria for exclusion. Form-IV)

IX. CRITERA FOR ASSESMENT OF RESULT OF TREATMENT

Disappearance of headache and presenting clinical features i.e. (i) Unilateral, (ii) Pulsating,(iii) Moderate to severe nature, (iv) Aggravated by movement, (v) Nausea, (vi) Photophobia &(vii) Phonophobia will be considered as significant improvement.


Data on clinical symptoms, duration of attack and frequency of attack will be tabulatedand analysed using appropriate statistical tools.



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XIII. ETHICAL REVIEW

A. Institutional Ethical Committee (IEC): The proposal will be placed before InstitutionalEthical Committee (IEC) of trial center for getting clearance certificate before the projectis initiated. Patient’s information sheet and informed consent form will be submitted alongwith project proposal for approval by IEC.

B. Data and safety monitoring board: A Data and safety monitoring board (DSMB) at Hqrswill carefully monitor the data and side effects during the period of study and put in aplace where by prompt reporting of adverse events occur and take appropriate steps incase of any adverse events occur. The data will be reviewed for every 20 participantsincluded into the study and administered the trial drugs. The research team will reportimmediately to the PI and Data Monitoring Board 1) any life threatening conditionswhether they are perceived to be study related or not. The Board decides whether theadverse effects warrant discontinuation of the study protocol. Protocols will be written andapproved for the treatment of study related adverse events


A consolidated amount of Rs……. /- per visit will be paid to subject selected for trial.


Short-term two-day training will be provided to the Investigators involved in the trial atCCRAS Hqrs. New Delhi. The investigators will be detailed about the clinical trial conduct andlaboratory procedures in order to maintain the uniformity.


The Laboratory Investigations (Hematological /Biochemical, etc.), which are not availableat research Institutes should be conducted at identified reputed labs /Government Institutes underintimation to this Council following codal formalities.

345



OUT AURA (ARDHAVA BEDHAKA)

CONSENT FORM




Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “Assessment of Therapeutic Efficacy of Ayush-M Nasal Drops and Ayush-M capsule in the management of Migraine with out Aura (Ardhava Bhedaka )





Relationship ___________________________________


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Migraine (Ardhava Bedhaka) is as old as civilization, occupying 16% among clinicalclassification of headaches, has become a challenging problem to the present day physician. Theeis no satisfactory treatment available, since no drug is clearly superior then its potential side effectare also considered A clinical study conducted on 20 cases migraine to evaluate the effect ofNasya Karma with fresh leaf juice extracted from Acalypha indica Linn. (Haritamanjari,) alongwith internal medication of Panchagavya ghrta (Astanga Hradya, Uttara Tantra 7/18) reveledsignificant clinical improvement. Keeping the potential of Ayurveda into consideration, the presentstudy is aimed at evaluating an effective and safe remedy for the management and prevention ofmigraine.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 3 months to complete (2 months fortreatment and another one month for follow-up study). During this period, you are expected to visitthe hospital three times, once in a month during drug treatment and once at the end of 3rd monthduring follow up.

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination, Blood and urine samples will also be taken. This is to make sure that youare eligible for the study.

If you are found eligible, you would be put on trial treatment for two months.Initially for seven days nasal drops will be given to you for installation in nostril as perguidelines issued by physicians. Daily dose of oral treatment consist of two 500 mg.capsules twice a day for two months.

At each visit, you will be supplied with sufficient quantities of drugs to last untilyour next visit.


347





1. Centre: ………………..……….





6. Address ……………………………………..…………..........……………………………


1. Age below 20 years & upto 60 years

2. Both the sex

3. Five or more attacks of migraine (headache) without Aura lasting for 4-72 hours

4. Presence of two or more of the following features

i) unilateral,

ii) Pulsating,

iii) Moderate to severe

iv) Aggravated by movement and

5. Presence of one or more of the following features

i) Nausea,

ii) Photophobia,

348

iii)Photophobia



7. Less than five attacks of Migraine without Aura

Clinically diagnosed cases of (S.No. 8 – 16)

8. Tension headache

9. Cluster headache

10. Idiopathic stabbing headache

11. Exert ional headache

12. Headache due to systemic infection

13. Drug induced headache

14. Organic brain lesions

15. Any systemic disorders



If Sl. No. 1 to 5 is ‘Yes’ and Sl. No. 6 to 16 are ‘No’

If admitted, Sr. No. of the Subject: _____________________

Date: _______________ Signature of the Investigator: ___________________

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CASE RFPORT FORM II - HISTORY

1. Centre : ........................................



4. Name of the patient .............................................................................................................

5. Gender Male 1 Female 2

6. Address: ..............................................................................................................................









Exposed to allergens like dust, chemicals : ..............................................

Field work with physical labor : ..............................................................

Indicate nature of work : .........................................................................


11. Income per capita per month in rupees :

350

Chief complaints with duration Present (1) Absent (0)

12. Five or more attacks of Migraine (headache) Aura lasting for 4-72 hours

13. Clinical features

14. Unilateral headache

15. Pulsating,

16. Moderate to severe

17. Aggravated by movement

18. Nausea

19. Photophobia,

20. Phonophobia

21. Average frequency of attacks of migraine per month

Zero One Two Three More than Three

22. Average duration of attacks of migraine (hours)

Less than five hours five to ten hours more than 10 hours

Personal History

23. Diet: Veg 1 Non-veg 2 Lecto-veg 3

24. Sleep: Normal (1) Duration in hours :____________

Abnormal (2) Duration in hours :____________

If Abnormal specify ______________________________________

No (0) Yes (1)

(a) Initiation:

(b) Maintenance:

(c) Freshness in the morning:

351

25. Anxiety

26. Constipation

Addiction


If yes specify: (a) Quantity [packs] ________________

(b) Total Duration in years ____________


If yes specify: (a) Quantity__________





30. Any other(specify)________________

31. Prakriti:

Vataj 1 Pittaj 2 Kaphaj 3

Vataja-Kaphaj 4 Vata-Pittaj 5 Pitta-Kaphaj 6

Sannipataj 7

32. Systemic examination: Normal 1 Abnormal 2

If abnormal, specify abnormalities __________________________________________

Date: _______________ Signature of Investigator: _________________________

352





[0, end of the Ist Month, IInd Month, IIIrd Month]

1. Centre : ........................................




5. Gender: Male 1 Female 2

6. Address: ..............................................................................................................................



Clinical Symptoms Present (1) Absent(0)

9. Unilateral headache

10. Pulsating headache

11. Nausea

12. Photophobia

13. Phonophobia

14. Frequency of attacks during last one month

Zero One Two Three More than Three

15. Duration of migraine attacks (hours):

Less than five hours five to ten hours more than ten hours

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16. Adverse reaction: Yes 1 No 2

If yes, details:_______________________




Continuing 1

Drop out 2 Reason: _____________________________

Died 3 Cause: _______________________________

Date: ________________ Signature of the Investigator: ______________________

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(BEFORE TREATMENT)

1. Centre : ........................................





6. Address: ..............................................................................................................................



9. Urine Examination: Routine____________ / Microscopic___________

10. TC (Cells/Cmm.)_____________________

11. DC: P (%)______ L (%)______ E (%)______ M (%)______B (%)______

12. Hb (g/dl) ______________

13. ESR (1st hour.)(mm) ______________

14. Blood Sugar – PP (mg./dl)______________

15. B. Urea (mg./dl) ______________


17. Uric acid (mg./dl) _______________

18. Lipid profile ______________

19. Liver function tests ______________

Date: ______________ Signature of Investigator _________________________

355

Drug : Study Code:


DOUBLE BLIND PLACEBO CONTROLLEDCLINICAL EVALUATION OF “AYURVEDIC CODED

DRUG (AYUSH MANAS)” IN THE MANAGEMENT OF“MANASA MANDATA (MENTAL RETARDATION)”


356

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357

I. BACKGROUND

Manasa mandata is a condition in which the normal growth of the child is affected andthis could be equated with mental retardation due to various reasons. According to Ayurveda thisdeficiency occurs due to beeja dosha where the parents of the child might have had incompatibleand improper diet and habits, during and before their conjugation. According to ayurvedicconcepts vata or vayu (bodily bioforce) is the self-generating and self-propagating energy, whichis responsible for the conduct, regulation and integration of all vital functions and the structures ofthe body. This vital force when imbalanced due to the above factors affects the development offetus and ends up with serious deformities to the child. Because if vata is in imbalanced stage,definitely child will become mentally and/or physically abnormal. Ayurveda has mentioned the roleof doshaja (both sareeraka & manasika) and ajantuja factors in development of the diseasepathogenesis. The rajoguna &tamoguna (manasika dosha) along with vata, pitta, & kapha(sareeraka dosha) will play an important role for the development of this disease.

Severity of Mental Retardation

Depending on the severity of intellectual impairment ICD –10 classifies the mentalretardation in to following degrees.

F 70 Mild mental retardation IQ of 50-69

F 71 Moderate mental retardation IQ of 35-49

F 72 Severe mental retardation IQ of 20-34

F 73 Profound mental retardation IQ < 20

The Intelligence quotient (IQ) score is used in the measurement of intelligence. IQ tests aredesigned in such a fashion that an average individual gets a score of 100. As mentioned earlier, anIQ of less than 70 is the criterion for falling in the range of mental retardation. Common IQ teststhat are used in India are Binet Kamat Test (BKT), Vineland Social Maturity Scale (VSMS),Development Assessments scale for Indian Infants (DAS II), Seguin Form Board (SFB) and MalinIntelligence Scale for Indian Children (MISIC).

II. OBJECTIVE

To study the efficacy of Ayush Manas for one year, in children with mental retardation interms of improving their intellectual function as measured by the IQ or SQ.


DOUBLE BLIND PLACEBO CONTROLLED CLINICAL EVALUATION OF“AYURVEDIC CODED DRUG (AYUSH MANAS)” IN THE MANAGEMENT OF

“MANASA MANDATA (MENTAL RETARDATION)”

358

III. SAMPLE SIZE &METHODS

Study design: 12 months prospective double blind placebo controlled design is proposed. Patientswhile e & f are optional / to selected patients.

Sample Size: Sample size would be 60 in active drug arm and 60 in the placebo group.

Drug/Dosage/ Duration

The subjects will be randomized to ayush Manas and placebo in a 1:1 ratio withapproximately 60 patients assigned to each group. Active treatment will be given for one year.

The drug Ayush Manas (250/tab) will be given at a dose of 2 tablets tid with water, whichcontains equal parts of brahmi, manduka parni, jyothishmathi and ashwagandha.

Study procedures

Subjects will visit the investigator six times during the trial. The initial visit is screening phase(visit 0), and subsequently after 1 to 4 weeks of initial wash out period (visit 1), after 3 months(visit 2), 6 months (visit 3), 9 months (visit 4), 12 months (visit 5) and 6th visit will be at 15th

month. Visit 0 will be considered as the screening, visit I will be considered, as the baseline visitwhere the trial begins and visit 5 will be the end of active treatment. On visit 1(base line visit), theinvestigator after ensuring compliance with inclusion and exclusion criteria will propose the study tothe patient and obtain informed consent for each subject from the parent or guardian. A completemedical history will be obtained. This will include patient demographics, significant past and presentillness or surgical procedures, concomitant medication data and VSMS – Malin’s version. Aphysical examination will be done and include the recording of height, weight heart rate and bloodpressure. Diagnosis of Mental Retardation will be made according to VSMS – Malin’s versioncriteria for Mental Retardation. Laboratory investigations will be done as per CRF (case recordingfile) at base line (visit 1), after 3 months (visit 2) and at the end of the active treatment (visit5).

IV. CRITERIA FOR INCLUSION

1. Children of either sex aged in between 6 to 13 years.

2. Children with mild to moderate Mental Retardation.

V. CRITERIA FOR EXCLUSION

Children with a history of peptic ulcer disease, any gastric or duodenal surgery,gasterointestinal (GI) bleeding or other GI disorders.

1. Children with severe infection and/or clinically significant hepatic, respiratory, renal, cardiacor hematological disorders.

2. Children with abnormal laboratory values at admission in to the study: serum creatinine 1.2mg/dl, SGOT, SGPT >2times uppr limit of normal; serum bilirubin or Alkaline phosphatase>1.5 times upper limit of normal.

359

3. Subject’s guardian who cannot be relied upon to comply with the test procedures or areunwilling to give informed consent.

4. The Children had any intramuscular, intra-articular or intravenous carticosteroids within 4weeks prior to study entry.

5. The Children has likelihood of requiring treatment during the study period with drugs notpermitted by the study protocol.

6. The Children with a history of recent and clinically significant drug abuse.

7. The Children with pre-existing blood dyscrasias, eg., bone marrow hypoplasia, leukopenia,thrombocytopenia etc.

8. The Children is unlikely to comply with protocol, eg., un cooperative attitude, inability toreturn for follow-up visits, and unlikelihood of complete study.

9. Children in whom another investigational drug was used with in 3 months prior to entry inthis study.

10. Children with mental retardation suffering with active epilepsy (H/o attack in last 3 months).

11. Children to whom Binet Kamat Test (BKT) can’t be administered for any reason such asspeech delay, severe hyperkinesias etc.

VI. CRITERIA FOR WITHDRAWAL

A discontinuation occurs when an enrolled subject ceases participation in the study,regardless of the circumstances, prior to completion of the study. The reason for withdrawalshould be recorded in the CRF, dated and signed. Efforts should be made to ascertain the reasonfor discontinuation.

Discontinuation can be due to:

1. Non-compliance with the study medications and specified visits

2. Serious clinical events requiring specific treatment

3. At subject’s/ guardian’s request.

The final evaluation required by the protocol at the end of the study, will be performed atthe time of study discontinuation.

VII. ROUTINE INVESTIGATION AND ASSESSMENT

The following laboratory tests will be performed on at base line (visit 1), after 3 months(visit 2) and at the end of the active treatment (visit5).

360

The laboratory tests include:

Hematology: Hemoglobin, haematocrit, RBC count, TLC, DLC, platelet count, erythrocytesedimentation rate (ESR), bleeding time, clotting time, prothrombin time.

Biochemistry: Total bilirubin, SGPT, SGOT, alkaline phosphotase, creatinine, blood sugar,serum protein and albumin.

Urinanalysis: Albumin, microscopic haematuria, Urine for abnormal metabolites.

The laboratory test results will be recorded in CRF.

VIII. CLINICAL ASSESSMENT

Using study instruments in each visit will assess all Children who fulfill the inclusion andexclusion criteria and whose parent/guardian provides written informed consent.

Instruments - a. Detailed clinical proforma for Mental Retardation

b. Binet Kamat Test (BKT)

c. Vineland Social Maturity Scale (VSMS) – Indian adaptation by Malin

d. Maladaptive Behavior Scale (Part II of ABS of AAMR)

e. Seguin Form Board (SFB)

f. Malin’s Intelligence Scale for Indian Children (MISIC)

a, b, c & d will be administered to all the patients while e & f are optional / to selected patients.

SAFETY RECORDING

a. Adverse Events

All adverse events observed or reported by patients will be recorded in the CRF withinformation about severity (i.e., whether mild, moderate or severe) and possible relation to thestudy medication. Any serious adverse effects must be notified immediately to the study monitor.

b. Safety Measures

Safety evaluation will perform by recording clinical adverse events at randomization(baseline) and at the subsequent clinical visits. Further adverse events will be classified accordingto their type, severity and possible relationship to treatment. At Visit 1 the subject’s medical historywill be recorded. At monthly visits vital signs (body temperature, pulse, blood pressure) will berecorded and a physical examination will be performed (Abnormal Lab reports listed in appendix3).

361

IX. TRIAL MONITORING AND DATA ANALYSIS

A qualified statistician will perform the statistical analysis. All available data will be used inthe analysis. In general all statistical tests will be performed at the 5% level of significance.

X. ETHICAL REVIEW

Ethics Committee: The study will be performed in accordance with the principles statedin the Declaration of Helsinki (enclosed Appendix 2). Ethical approval of the study protocol willbe obtained from the Ethics committee at institutions where the study will be conducted before thestudy is undertaken. The opinion of the Ethics Committee should be dated and given in writing.Whenever possible, the names and titles of the members attending the Ethics Committee meetingshould be appended. The approval must clearly identify the protocol and other documentssubmitted for review, by title and study code.

XI. TRAVELING EXPENSES FOR RESEARCH SUBJECTS

A consolidated amount of Rs.100/- per visit i.e., on the 1st day of recruitment afterscreening, 1st, 2nd, 3rd month (4 times)

XII. TRAINING TO INVESTIGATORS AND PERSONS INVOLVED


XIII. LABORATORY INVESTIGATIONS

The Laboratory Investigations (Haematological /Biochemical, etc.), which are not availableat research Institutes should be conducted at identified reputed labs /Government Institutes underintimation to this Council following codal formalities.

362


CLINICAL EVALUATION OF “AYURVEDIC CODED DRUG(AYUSH MANAS)” IN THE MANAGEMENT OF “MANASA MANDATA

(MENTAL RETARDATION)”



The research study in which patient participation is suggested aims to assess the efficacyand safety of a new drug called AYUSH MANAS, a herbal product.

Currently no available drug has proven efficacy to improve the overall intellectualfunctioning. Many patients seek alternative methods of treatment (complementary medicine). Thereis thus a definite need to scientifically assess some of these treatment modalities. Though there areno published data available on the efficacy of these herbs in mental retardation, the long claimedusage in complementary medicine in India, claimed efficacy in mental performance, the apparentsafety profile makes it worthwhile studying in a placebo controlled randomized double blind trial.

The individual components of AYUSH MANAS have been studied in India & abroad invarious institutes in open clinical trials for disorders of the nervous system, memory improvement,and development of immunity.

Explanation of procedures to be followed

Study procedure

I agree to return to this institute for examinations and evaluations of my child’s response totreatment. At this initial visit my child’s medical and psychiatric history, current condition andeligibility to enroll in this study will be evaluated. Approximately 5 more visits will be required toassess my child throughout this study. Visits will take approximately one or two hours.

During these visits, a complete clinical assessment including physical examination,psychological tests, & behavior rating scales, compliance with therapy and reporting of anyadverse reactions will be recorded.

Laboratory tests will be performed on first, second and last visits.

My child will be receiving either AYUSH MANAS or placebo (inactive drug). Neither myphysician nor I will know what medication my child is receiving. The physician will however beable to obtain this information, quickly if needed.

Expected duration of the study and number of patients expected to participate

My child will be one of 120 patients who will participate in this study. The studymedication will be administered orally daily for a period of one year.

Possible risks

Based on our clinical experience the drugs included in AYUSH MANAS have shown noside effects for short and long-term therapy.

363

Problems and side effects, which are not known at this time, could occur. I will be told ofany changes in the way the study will be done and of any newly identified risks to which my childmay be exposed.

I shall inform the physician about any illness that my child may have suffered in this studyperiod and the treatment required for it.

Patient participation

Participation in this study is entirely voluntary. If I do not desire to enroll my child for thestudy the child’s treatment will continue as per the routine of the institute.

Possible benefits of the study

The costs of the all tests, examinations and medical care required as a part of this studyare to be provided free of cost to me. My child may respond favorably to treatment and othersmay benefit from the overall conclusions to be drawn from the results of this study. There is noguarantee that my child will benefit from participating in this study.

Withdrawal from this study

The investigator in charge of this study can remove my child from the study without myconsent based on his/her judgment to improve my child’s medical care or my failure to follow thestudy schedule.

Compensation

If my child is injured as a direct result of taking part in this study, I understand thatmedical treatment and other related costs should be made available by CCRAS, New Delhi.

Right to withdraw from the study

I am free to leave this study at any time without giving any reason. My decision of notparticipating in this study or to leave the study in between shall not affect my child’s future medicalcare.

Confidentiality

The records obtained during the study as well as related health records will remain strictlyconfidential at all times. However, I understand that these will need to be made available toCCRAS, New Delhi, to other doctors/scientists of this study and if required to the drug regulatoryauthority. The information disclosed will remain confidential. The results of the treatment, includinglaboratory tests, photographs may be published for scientific purposes provided my child’s identityis not revealed.

Data protection: Use of data collected from this study

My child’s personal data, which may be sensitive, will be collected and processed only forresearch purposes in connection with this study. By taking part in this study, I agree not to restrictthe use of any data even if I withdraw.

364


CLINICAL EVALUATION OF “AYURVEDIC CODED DRUG(AYUSH MANAS)” IN THE MANAGEMENT OF “MANASA MANDATA

(MENTAL RETARDATION)”


(By parent/guardian of the patient)

I,…………………………………………………………………………………………Father/Mother/Guardian of………………………………………, exercising my free power of choicegive my consent on my as well as my child’s behalf to be included in this study on one-yearprospective double blind placebo controlled clinical evaluation of “Ayurvedic coded drug (AYUSHMANAS)” in the management of “Manasa Mandata (Mental Retardation)”. I have read, or hadread to me, the above information before signing this consent form. I have been provided ampleopportunity to ask questions and have received answers that fully satisfy those questions. I havebeen informed to my satisfaction by the attending physician the nature and purpose of the study.

I understand that the clinical details and information recorded as part of the study will bekept confidential.

I am also aware of my right to withdraw out of this study at any time during the course ofthe study without having to assign the reason for doing so.

Signature of the Father/Mother/Guardian Date: ________________

Signature of the Physician Date: ________________

Signature of impartial witness Date: ________________


365

CENTRAL COUNCIL FOR RESEARCH IN A YURVEDA AND SIDDHA

CLINICAL EVALUATION OF HERBOMINERAL PREPARATIONS IN THEMANAGEMENT OF MANASA MANDATA (MENTAL RETARDATION)

CASE REPORT FORM – I SCREENING


1. Name of the patient : ______________________________________________________

2. Address: ______________________________________________________________________________________________________________________________

3. Centre: _______________________________________________________________


5. Patient No. ______________________________________________________________


Third Fourth


1. Age between 5-16 years of either sex 1 0

2. Duration of disease up to 10 years 1 0

3. Presence of cardinal symptoms of diseases 1 0

CRITERIA OF EXCLUSION

4. Age below 5 and above 16 years 1 0

5. Duration more than 10 years 1 0

6. Patients with uncontrolled epilepsy, hyperkinesis, 1 0psychosis, tuberculosis and organicity

7. Others (specify)_________________________________________

A patient will be admitted for treatment,

If ‘Yes’ to 1 – 3 and ‘No’ to 4 – 7 above

No: _ _ _ _ _ _ _ _ _ _ _ _

Date: _____________ Signature of the Investigator _______________________

366




CASE RFPORT FORM II - HISTORY

1. Name of the patient : ______________________________________________________

2. Address : ______________________________________________________________________________________________________________________________


4. Centre : __________________________________________________________________

5. Code No. (of clinical trila) :

6. Patient No.

7. Group No. First 1 Second 2

Third 3 Fourth 4

8. Age in patient in years : _______________

9. Educational status:

Illiterate 1 Read and write 2 Primary 3

Middle school 4 High school 5 College 6

Others (specify) 7 INA 8

10. Occupation

Desk work 1 Field work 2




367

Total income of the family in rupees : .......................................................



Chief complaints with duration Yes (1) No (0)

13. Delayed milestones 1 0

14. Speech handicap 1 0

15. Seizures 1 0

16. Mental age not proportional with chronological age 1 0

17. Adaptive behavior Impaired 1 Not impaired 0

18. Hyperactivity present 1 absent 0

19. Maladaptive signs (tick if present)

Twitches & tics

Silly giggling

Dribbling of the saliva

Destructive & harmful

Inopportune laughing/crying/shouting

Fixed eyes

Lack of personal hygiene

History of present illness:

20. Onset of disease Acute 1 Insidious 2

21. Duration of disease ______________

22. Treatment given so far :

Ayurvedic medicine 1 Modern medicine 2 Unani 3

Homoeopathy 4 Siddha 5 Mixed 6

368

Medicines given ________________________ Results obtained ______________________

23. Factors aggravating the disease/chief complaints ___________________________________

24. Factors relieving main complaints_______________________________________________

25. History of past illness having relation with present illness

Yes 1 No 2

If yes, specify _____________________________________________________________

Family History if any Yes (1) No (0)

26. Mental disease 1 0

27. Mental retardation 1 0

28. Consanguineous marriage 1 0

Personal History

29. Diet: Veg 1 Non-veg 2 Lacto-ova veg 3

30. Sleep: Good 1 Disturbed 2 Insomnia 3

31. Emotional stress Yes 1 No 2

32. Bowel Habit Regular 1 Constipation 2 Loose motion 3

33. Addiction Yes 1 No 2

If yes, specify _____________________________________________________________

34. Prakriti


Vataja-Kaphaj 4 Vata-Pittaj 5 Pitta-Kaphaj 6

Sannipataj 7

369

35. Manas Prakriti

Sattva 1 Rajas 2 Tamas 3

Sattva-Rajas 4 Sattva-Tamas 5 Rajas-Tamas 6

Sama 7

Physical Examination:

Build Lean 1 Medium 2 Heavy 3

36. Body weight Kg: _________________

37. Blood Pressure (Systolic): _________________

38. Blood Pressure (Diastolic): _________________

39. Body temperature: _________________

40. Respiration: _________________


41. Cyanosais 1 0

42. Anaemia 1 0

43. Jaundice 1 0

44. Pigmentation 1 0

45. Clubbing of fingers 1 0

46. Deformities 1 0

47. Lymphadenopathy 1 0


48. CVS with chest 1 2

If abnormal, specify abnormalities_______________________________________________

49. CNS 1 2

If abnormal, specify abnormalities__________________________________

370

50. Digestive System 1 2


51. Urogenital System 1 2


Samprapti (Pathogenesis) of the disease

52. Anubandhyashareerikadosha Vata 1 Pitta 2 Kapha 3

53. Anubandhashareerika dosha Vata 1 Pitta 2 Kapha 3

54. Anubandhya manasika dosha Rajas 1 Tamas 2

55. Anubandhamanesika dosha Rajas 1 Tamas 2

56. Ksheena shareerika dosha Vata 1 Pitta 2 Kapha 3

57. Ksheena manasika dosha Rajas 1 Tamas 2

58. Stages of disease (Rogakriya kala)

Sanchaya 1 Prakopa 2 Prasara Sthanasamshraya 3

Vyakti 4 Bheda 5

SROTAS PAREEKSHA

59. Pran Vaha Srota

Alpa Alpa Swasa (Shortened Breathing) 1

Atisrama Swasa (Increased respiration rate) 2

Abhikshna Swasa (Chyne stroke breathing) 3

Kupita Swasa (Vitiated breathing) 4

Sashula swasa (Dyspnoea with pain) 5

60. Udakavaha Srota

Jihva sosha (Dryness of tongue) 1

371

Oustha sosha (Dryness of lip) 2

Talu shosha (Dryness of palate) 3

Kantha shosha (Dryness of throat) 4

Kloma shosha (Excessive thirst) 5

Trishna (Thirst) 6

61. Annavaha Srota

Anannabhilasha (Lack of desire for food) 1

Aruchi (Anorexia) 2

Avipaka (Indigestion) 3

Chhardi (Vomitting) 4

62. Ras Vaha Srotas

Mukha vairsya (Bad taste in mouth) 1

Arasajnata (Tastelessness) 2

Hrillasa (water brash) 3

Gaurava (Feeling of heaviness) 4

Tandra (Stupor) 5

Anga marda (Body ache) 6

Jwara (Fever) 7

Pandu (Anaemia) 8

Avsada (Depression) 9

Klaibya (Loss of libido) 10

Karshya (Emaciation) 11

Agnimandya (Diminished appetite) 12

372

63. Rakta Vaha Srotas

Pidika (Boils) 1

Rakta Pitta (Bleeding from any of the orifice) 2

Mukha paka (Stomatitis) 3

Vidradhi (Abscess) 4

Charma raga (Skin disease) 5

Kamala (Jaundice) 6

64. Mamsa Vaha Srotas

Arubuda (Tumour) 1

Aljee (Phlyctenular conjunctivitis) 2

Gandamalaa (cervical lynphadenitis) 3

Upjivihika (Epiglotitis) 4

Adhimamsa (Protruberance of flesh/cancer/cyst) 5

Putimamsa (decayed flesh/gangrene) 6

65. Medo Vaha Srotas -

Maladhykya (Excess of excreta) 1

Hastapada daha (Burning sensation in the palm and sole) 2

Hastapada suptata (Numbness of the palm and sole) 3

Tandra (Stupor) 4

Dehachikkanata (Greasiness of the skin) 5

Alasya (Lethargy) 6

66. Asthi Vaha Srotas -

Adhyasthii (Hypertrophy of bone) 1

373

Adhidanta (Redundant tooth) 2

Dantshoola (Toothache) 3

Asthi shoola (bone pain) 4

Kesha, lorna, nakha, samshru vikara 5(Any defects of hair, hair follicles, nails and mustaches)

67. Majja Vaha Srotas -

Parva shoola (Pain in the Interphalangeal joints) 1

Bhrama (Vertigo/Giddiness) 2

Moorchh (Syncope) 3

Mithyajnana (Illusion) 4

68. Shukra vaha srotas -

Klaivya (Sterility/impotence) 1

Aharshan (Loss of erection) 2

Garbha pata (Abortion) 3

Santana vikriti (Congenital deformity of the children) 4

69. Manovaha srotas

Manovibramsha 1

Budhivibramsha 2

Samjavibramsha 3

Smritivibramsha 4

Bhktivibramsha 5

Sheelavibramsha 6

Chesta vibramsha 7

Acharavibramsha 8

374

70. Artava vaha srotas -

Anartava (Amenorrhoea) 1

Vandhyatva (Sterlity) 2

71. Mutra-vaha srotas -

Bahumutrata (Polyuria) 1

Atibadhta (Urination with obstruction) 2

Prakop mutra (Defective Urination/Difficulty in micturition 3

Alpaalpa (Scanty urination) 4

Aabhikshna (Constant/repeated urination) 5

Bahulamutrata (Urine with prostatic secreation) 6

Sashoola mutrata (Painful micturition) 7

72. Pureeshavaha srotas -

Alpaalpa pureesha (Scanty defecation) 1

Sashoola pureesha (Painful defecation) 2

Atidrava pureesha (Diarrhoea) 3

Atigrathita yukta pureesha (Scybala) 4

73. Sweda vaha srotas -

Aswedan (Loss of perspiration) 1

Atiswedana (Profuse sweating) 2

Parushya (Roughness of the skin) 3

Lomaharsha (Thrill) 4

Aangaparidaha (Burning sensation in the body) 5

375

74. Investigations

Clinical assessment

75. Provisional diagnosis Final diagnosis

76. Medical management

77. Principle drug therapy

Drug Dose Vehicle Diet

Duration of treatment

78. Summary of findings

79. Results: Good response 1 Fair response 2

Poor response 3 No response 4

Dropout 5 LAMA 6

Death 7

Date:____________ Signature of Investigator___________________________

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CLINICAL EVALUATION OF HERBOMINERAL PREPARATIONS IN THEMANAGEMENT OF MANASA MANDATA (MENTAL RETARDATION)

CASE REPORT FORM – III INVESTIGATION

1. Name of the patient: ________________________________________________________

2. Address: ______________________________________________________________________________________________________________________________

3. Centre: __________________________________________________________________

4. Code No. (of clinical trial):

5. Patient No.


7. Age of patient in years: _____________________________________________________

Investigations

Investigations At the time of admission At the time of discharge

8. URINE: Routine & Microscopic

9. Stool: Macroscopic & Microscopic

HAEMA TOLOGICAL INVESTIGATIONS

10. HB %

11. T.L.C. (in thousands/Cmm)

12. D.L.C.

Polymorphs : . . . . . . . . . . %

Lymphocyte : . . . . . . . . . . %

Basophil : . . . . . . . . . . %

Eosinophil : . . . . . . . . . . %

377

13. E.S.R. : 1 Hr . . . . . . . mm

: 2 Hr . . . . . . . mm

Biochemistry:

14. Total proteins (gm % )

15. Alkaline phosphatase . . . . . . . . . IU/L

16. S.G.O.T . . . . . . . . . IU/L

17. S.G.P.T . . . . . . . . . IU/L

18. S. Bilirubins . . . . . . . . . mg/100 ml

19. Urea . . . . . . . . . mg/100 ml

20. S. Creatinine . . . . . . . . . mg/dl

Special Tests

21. Urinary catecholamines

22. CT Scan for Head

23. EEG

Note: Only such investigations are to be undertaken for which facilities exist in the Institutes/Centres/Units themselves, unless exempted.

24. Objective test

(i) Binet Kamat test

(ii) Seguin Form Board Test

(iii) Vineland Social Maturity Scale

385

Drug : Study Code:


SAMANA THERAPY VIS-A-VIS PANCHAKARMATHERAPY IN THE MANAGEMENT OF GRIDHRASI

(SCIATICA)


386

Blank

387

I. BACKGROUND

Pain starting from the gluteal region and spreading down the back of the lower limb andradiating upto the foot is the main symptom of the Gridhrasi (Sciatica). There will be a limp gaitand difficulty in sitting. If pain is severe, the patient may not be able to move from bed. The painincreases by coughing or sneezing. The patient suddenly seized with immobilizing and shooting paindown the leg, starting from lower back.

The disease mostly affects the early and middle aged people. Occupations like heavyweight lifting, continuous pressure on the back etc. are also main causative factors.

ETIOPATHOGENESIS

According to Ayurveda, in Gridhrasi1, the main vitiated Dosha is Vata. In AshtangaHridaya and Sushruta Samhita, the descriptions of Gridhrasi are identical. However, Caraka’sdescription differs. It classifies Gridhrasi into two types namely Vataja and Vatakaphaja.Caraka’s description is very much similar to modern concept. According to Ayurvedic conceptsalso, the origin of the disease is at Katipradesha (Lumbo - Sacral region).

Inspite of the fact that the spinal diseases are difficult to be cured, sciatic pain is not somuch harmful as other neurological conditions. Ayurvedic concept of treatment for Gridhrasi(Sciatica) is more effective and suitable as compared to modern mode of treatment. On prolongeduse also, there is no side effect with Ayurvedic regimen of treatment. Several single and compoundherbal preparations like Bhallataka (Tripathy et. al., 1965). Nirgundi (Jain et. al., 1976) andHingutriguna Taila (Prem Kishore et. al., 1986) etc. have shown good response in themanagement of Gridhrasi (Sciatica).


SAMANA THERAPY VIS-A-VIS PANCHAKARMA THERAPY IN THEMANAGEMENT OF GRIDHRASI (SCIATICA)

References

1. Charaka Samhita, Chikitsa Sthana Chapter– 28, Vidyotini Hindi Vyakhya by Vd. AmbikadattaShastry, Choukhamba Orientalia, Varanasi

2. Harrison’s Principles of internal medicine, 14th Edition, International Editions, 1998, Publishedby Mc Graw-Hill CompaniesInc.pp1208-1209

3. Ambika Dutta Sashtri (1989) Susruta samhita (text with Hindi commentary) Nidana Sthana,Chapter – 1, VIIth Edition Chaukhamba Sanskrit Series Office, Varanasi.


388

Since inception, Indian Institute of Panchakarma has been concentrating ClinicalResearch Trials on Gridhrasi in order to find out an effective line of treatment. Several Single andCompound Ayurvedic preparations had been tried. Following are the main drugs in which ClinicalTrials have been already conducted in past. All the trials have shown significant result in themanagement of Gridhrasi cases.

Typical pain radiation, caused due to irritation of the 4th and 5th lumber and 1st sacralroots, from the sciatic nerve extending mainly down the posterior aspect of the thigh and posteriorand lateral aspects of the leg is termed as Sciatica. Twinkling, paresthesia and numbness of orsensory impairment of the skin, soreness of the skin and tenderness along the nerve alsoaccompanies the classic sciatic pain and on physical examination reflex loss, weakness, atrophy,fascicular twitching and occasionally stasis oedema may occur is the motor fibres of the anteriorroot are involved.

Mild attacks least for a week or two. Other cases happen to be more chronic andprovide a history of remitting attacks. Favorable cases, rested absolutely on hard bed, mayrecover with 4 – 6 weeks but recurrences are frequent. Foot drops seldom recovers completely.Pelvic tractions help in some cases with disc lesions. Massage, spinal exercise and heat applicationprovide comfort and hence are useful. If there is no improvement by providing bed rest and thereare recurrent disabling attacks, surgical removal of the disc is suggested.

II. OBJECTIVES

The study aims to assess the Comparative Clinical Evaluation of Dasamoola Bala Kwatha(Internal) along with Dasamoola Bala Taila (Internal and External) in one group andPanchakarma Therapy with its different procedures in another group in the management ofGridhrasi (Sciatica). The drug Dasamoola and Bala are well known for their Vataharaproperties.

III. CENTER:



Sample Size: 100 cases

No of Groups: Two groups

Trial Drug/Dosage/Duration

Group – I: Samana Chikitsa

a). Dasamoola Bala Taila – 10 ml. to 15 ml. thrice daily X 14 days.

i). Dasamoola Bala Kwatha – 10 – 15 ml. thrice daily X 14 days.

389

ii). Nirgundi Patrapotala Sweda after Abhyanga with Dasamoola BalaTaila X 14 days.

b). Virechana X 1 day with Eranda Taila 30 ml., after completing thePatrapotala Sweda

Group – II: Panchakarma Therapy

a). Snehapana with Dasamoola Bala Taila for 7 days

b). Vashpa Sweda X 3 days

c). Viechana with Eranda Taila X 1 day

d). Samsarjana Karma X 7 days

e). Vaitarana Vasti X 7 days

No of Patient in each Group: 50 cases in each group

(Random allocation of selected cases in two different trial groups)

Type of Study: Single blind

Duration of Study: Samana Chikitsa for a period of 22 days while PanchakarmaChikitsa will continue for a total period of 25 – 26 days.

Follow Up: For a period of three months on a regular interval of fortnight, either withpostal correspondence or on personal appearance of the patient at the field station wherehe/she has been registered for the trial.


1. Age — 20 to 70 years

2. Sex — Either sex

3. Duration of illness — Upto 2 years

4. Radiating pain, starting from the gluteal region towards, the foot

5. Tenderness of the Sciatic Nerve course

6. Severe pain on squatting

7. Sensory change

8. Non-involvement of Urinary Bladder and Rectum

9. Positive straight leg raising sign

390



2. Duration of disease more than 2 years

3. Monoplegia

4. Paraplegia

5. Hip joint arthritis

6. T.B. Spine/Hip

7. Pelvic pathology

8. Traumatic lesion in lumbo - sacral region


1. Left against medical Advise (LAMA)

2. Development of complications due to presenting illness or otherwise

3. Aggravation of symptoms

Pronounced toxic side effects


Screening of the patient will be recorded as per case record form - I. Detailed clinicalhistory and physical examination of each patient will be recorded as per Part – II of the Proformaannexed. Pathological, Biochemical and other relevant investigations will be carried out as per Part– III of the proforma. The assessment of the results will be done according to effect of the TrialGroups on each of the sign and symptom. Each sign and symptom is graded and a numericalvalue is given for assessment of results. (as per case record form III).

Following criteria has been fixed for Routine Examination and Assessment.

1. Pricking pain 6

2. Pulling pain 6

3. Stiffness 3

4. Tenderness of sciatic trunk 6

5. Straight leg raising test/positive 54

jugular vein pressure test

6. Ankle jerk 2

391

7. Knee jerk 2

8. Plantar reflexes 2

9. Pressing power 3

10. Muscle wasting 3

11. Walking speed 3

12. Sensory impairment 2

13. Posture 8

Total 100

Symptoms were suitably graded to assess the degree of involvement. The assessment chartis annexed at Part – IV of the Proforma.


Result of treatment will be graded as follows:

1. Good Response : Complete relief in presenting symptomatology of the disease.

2. Fair Response : 75% and above relief of signs and symptoms.

3. Poor Response : 50% to 74% relief of signs and symptoms

4. No Response : No response in presenting clinical symptomatology of disease orotherwise.

X. TRIAL MONITORING AND DATA ANALYSIS

The progress of the study will be monitored by team comprising of Clinicians, Pathologists,Biochemists, Radiologists and Statisticians.

XI. STATISTICAL ANALYSIS

Before treatment and after treatment, data signs/symtoms and other parameters taken intoaccount for diagnosis and assessment of result of treatment will be tabulated and analyzed usingsuitable statistical methods.

XII. TRIAL MONITORING AND DATA ANALYSIS


392



XIV. TRAVELING EXPENSES FOR RESEARCH SUBJECTS


XV. TRAINING TO INVESTIGATORS AND PERSONS INVOLVED


XVI. LABORATORY INVESTIGATIONS


393






Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “Samana therapy vis-a-vis panchakarma therapy in the managementof gridhrasi (sciatica)”





Relationship ___________________________________


394


SAMANA THERAPY VIS-A-VIS PANCHAKARMA THERAPY IN THEMANAGEMENT OF GRIDHRASI (SCIATICA)



Pain starting from the gluteal region and spreading down the back of the lower limb andradiating upto the foot is the main symptom of the Gridhrasi (Sciatica). There will be a limp gaitand difficulty in sitting. If pain is severe, the patient may not be able to move from bed. The painincreases by coughing or sneezing. The patient suddenly seized with immobilizing and shooting paindown the leg, starting from lower back.

The disease mostly affects the early and middle aged people. Occupations like heavyweight lifting, continuous pressure on the back etc. are also main causative factors.

According to Ayurveda, in Gridhrasi, the main vitiated Dosha is

Vata. In Ashtanga Hridaya and Sushruta Samhita, the descriptions of Gridhrasi areidentical. However, Caraka’s description differs. It classifies Gridhrasi into two types namelyVataja and Vatakaphaja. Caraka’s description is very much similar to modern concept.According to Ayurvedic concepts also, the origin of the disease is at Katipradesha (Lumbo -Sacral region).

Inspite of the fact that the spinal diseases are difficult to be cured, sciatic pain is not somuch harmful as other neurological conditions. Ayurvedic concept of treatment for Gridhrasi(Sciatica) is more effective and suitable as compared to modern mode of treatment. On prolongeduse also, there is no side effect with Ayurvedic regimen of treatment. Several single and compoundherbal preparations like Bhallataka (Tripathy et. al., 1965). Nirgundi (Jain et. al., 1976) andHringutriguna Taila (Prem Kishore et. al., 1986) etc. have shown good response in themanagement of Gridhrasi (Sciatica).


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approxim. Samana Chikitsa for a period of 22 dayswhile Panchakarma Chikitsa will continue for a total period of 25 – 26 days.

During treatment period, you are expected to visit the hospital for clinical and physiologicalassessment.

395


If you are found eligible, you would be put on treatment for Samana Chikitsa fora period of 22 days while Panchakarma Chikitsa will continue for a total period of 25 –26 days.



396

CENTRAL COUNCIL FOR RESEARCH IN AYURVEDA & SIDDHA

SAMANA THERAPY VIS – A – VIS PANCHAKARMA THERAPY IN THEMANAGEMENT OF GRIDHRASI (SCIATICA)


BEFORE TREATMENT


1. Name of the patient: .................................................... Age: ................. Sex: ...................

2. Address: ...............................................................................................................................

3. Centre:


5. Patient No.

6. Group No


7. Age between 12 – 70 years 1 0

8. Sex – Either sex 1 0

9. Duration of illness upto 2 yrs. 1 0

10. Regarding pain starting from gluteal region 1 0

11. Tenderness of sciatic nerve course 1 0

12. Severe pain on squatting 1 0

13. Positive straight leg raising sign 1 0

CRITERIA FOR EXCLUSION Yes No

14. Age below 12 and above 70 years 1 0

15. Duration of the disease more than 2 years 1 0

397

16. Monoplegia 1 0

17. Paraplegia 1 0

18. Hip joint arthritis 1 0

19. T.B. Spine/Hip 1 0

20. Pelvic pathology 1 0

21. Traumatic lesion in lumbosacral region 1 0

Date: ________________ Name of Investigator: _____________________

398





1. Name of the patient : ............................................................ Age ............ Sex .................

2. Address : ..............................................................................................................................


4. Centre :


6. Patient No.

7. Group No

8. Age of Patient (in years)


Illiterate Read and write Primary










399


Christian 4 Parsi 5

Chief Complaints with Duration (as indicated in days)


14. Sphik sula/Katisula/Prishta sula 1 0

15. Urasula (Pain on back of thigh) 1 0(Sciatic Course)

16. Janghasula (Pain in calf muscle) 1 0

17. Padasula (Pain in foot) 1 0

18. Pain on raising from squatting 1 0

19. Thota (Pricking pain) 1 0

20. Graha (Pulling pain) 1 0

21. Spandana (Twitching) 1 0

22. Walking difficulty 1 0

23. Stambha (Stiffness) 1 0

24. Supti (Numbness) 1 0

25. Nidranasa (Distrubed sleep) 1 0

History of Present Illness


Duration of disease (in days)

27. Treatment given so far: Ayurvedic medicine 1 Modern medicine 2

Unani 3 Homoeopathy 4

Any other, specify: .......................................................................................................................

Spell out the medicines given and results obtained: ......................................................................

400

28. Factors aggravating the disease/chief complaints

Drug 1 Diet 2 Cold Climate 3

Tropical Climate 4 Damp climate 5 Sea shore 6

Positive factors may be spell out: ....................................................................................

29. Factors relieved main complaints

Drug 1 Diet 2 Cold Climate 3

Tropical Climate 4 Damp climate 5 Sea shore 6

Positive factors may be spell out: ....................................................................................

Yes No

30. Past illness, having relation with present illness 1 0

If yes, specify .......................................................................................................................

31. Hypertension 1 0

32. Diabetes mellitus 1 0

33. Bronchial Asthma 1 0

34. Cancer 1 0

35. Cardio vascular disease 1 0

36. Tuberculosis 1 0

Others (specify) ....................................................................................................................

Personal History

37. Diet Veg. 1 Non-Veg 2 Lacto-Ova Veg. 3

38. Sleep Good. 1 Distrubed 2 Insomnia 3


40. Bowel habit Regular 1 Constipation 2 Hard Stool 3

Loose Stool 4

401

41. Dependency Yes 1 No 2

If yes, specify: ......................................................................................................................

42. Prakriti

Vata 1 Pitta 2 Kapha 3


Sannipataja 7

43. Manas Prakriti


Sattva-Rajas 4 Rajas-Tamas 5 Sattva-Tamas 6

Sama 7




If abnormal, specify abnormalities: ........................................................................................

46. Body weight (in Kgs.)



49. Body temperature

50. Pulse

51. Respiration

Present Absent

52. Cynosis 1 0

53. Anaemia 1 0

54. Jaundice 1 0

402

55. Pigmentation 1 0

56. Clubbing of fingers 1 0

57. Deformities 1 0

58. Lymphadenopathy 1 0

If any, specify .......................................................................................................................


Present Absent

59. C.V.S. with chest 1 0

If any, specify .......................................................................................................................

60. C.N.S. 1 0

If any, specify .......................................................................................................................

61. Respiratory system 1 0

If any, specify .......................................................................................................................

62. Digestive system 1 0

If any, specify .......................................................................................................................

63. Uro-Genital system 1 0

If any, specify .......................................................................................................................

Local Examination

Yes No

64. Tenderness on sciatic trunk 1 0

65. Straight leg raising test 1 0

(Sakthi ulkshepa vaishamya) 1 0

66. Defective posture (Dehavakrata) 1 0

403

67. Sensory impairment 1 0

68. Stiffness (Stambha) 1 0

69. Swelling (Sotha) 1 0

70. Muscle wasting (Mamsa sosha) 1 0

Samprapti (Pathogenesis) of the disease according to Ayurvedic Concept

71. Anubandhya dosha – Vata: Vyana 1 Samana 2 Apana 3

72. Anubandha dosha – Kapha: Kledaka kapha 1

73. Dushya: Rasa 1 Mamsa 2 Asthi 3

Snayu 4 Kandara 5

SROTAS PARIKSHA

Mamsa Vaha Srotas: Yes No

74. Arubuda 1 0

75. Alajee (Phlyetenular conjunctivitis) 1 0

76. Ganda mala (Cervical lymphadenitis) 1 0

77. Upajihvika (Epiglotitis) 1 0

78. Adhimamsa (Protuberance of flesh/cancer/cyst) 1 0

79. Putimamsa (decayed flesh/Gangrenous) 1 0

Rasa Vaha Srotas

80. Mukha vairasya (Bad taste in mouth) 1 0

81. Arasyata (Tastelessness) 1 0

82. Hrillasa (Water in mouth) 1 0

83. Gaurava (Feeling of heaviness) 1 0

84. Tandra (Drowsiness) 1 0

404

85. Angamarda (Body ramps) 1 0

86. Jwara (Fever) 1 0

87. Pandu (Anaemia) 1 0

88. Avasada (Depression) 1 0

89. Klavya (Loss of libido) 1 0

90. Karshya (Emaciation) 1 0

91. Agnimandya (Diminished appetite) 1 0

Provisional Diagnosis:

Final Diagnosis:

Medical Management:

Principal Drug Therapy:

Dose —

Vehicle —

Diet —

Summary of findings:

102.Results:

Good Response 1 Fair Response 2

Poor Response 3 No Response 4

Drop out 5 LAMA 6

Death 7

Date: Signature of InvestigatorCounter Signature of Head of Deptt.

405


NEW DELHI


PROFORMA



2. Address : ..............................................................................................................................

3. Centre :


5. Patient No.

6. Group No

Parameters to Initially at the 1st 2nd 3rd Follow upbe taken for time of Assessment Assessment Assessment assessment admission – 15 days – 30 days – 45 days

(1) (2) (3) (4) (5) (6)

Clinical Parameters:

(A). Subjective symptoms

1. Pricking pain

Absent — 0

Mild — 2

Moderate — 4

Severe — 6

406

2. Pulling Pain

Absent — 0

Mild — 2

Moderate — 4

Severe — 6

3. Stiffness

Absent — 0

Mild — 1

Moderate — 2

Severe — 3

(B). Subjective signs:

a. Tenderness of the sciatic nerve

Grade – I (Patient says there is tenderness) — 2

Grade – II (Patient winces) — 4

Grade – III (Winces & withdraws the affected limb) — 6

b. Straight leg raising test (in degrees)

0 — 54

10 — 48

20 — 42

30 — 36

40 — 30

50 — 24

60 — 18

70 — 12

407

80 — 6

90 — 0

c. Ankle jerk

Present — 0

Exaggerated — 1

Absent — 2

d. Knee jerk

Present — 0

Exaggerated — 1

Absent — 2

e. Planter

Present — 0

Up going — 1

Absent — 2

f. Pressing power

a). Upto 10 Kg. — 3

b).10 to 20 Kg. — 2

c). 20 to 25 Kg. — 1

d). 25 and above — 0

g. Muscle wasting

Thigh:

a). Difference of 2.5 – 3.5 cm. — 0.5

b). Difference of 3.5 – 4.5 cm. — 1

c). Above 4.5 cms. — 1.5

408

Calf:

a). Difference of 1 – 1.5 cm. — 0.5

b). Difference of 1.5 – 2 cm. — 1

c). Above 2 cms. — 1.5

Measurement:

25 cm. above the medical mallcolus — R

— L

20 cm. above the knee joint line — R

— L

h. Walking speed (Time taken to cover 20 meters)

a). Upto 20 seconds — 0

b). 21 to 40 seconds — 1

c). 41 to 60 seconds — 2

d). Above 60 seconds — 3

i. Sensory impairment — 2

j. Posture — 8

a). No Complaint — 0

b). Patient can walk without difficulty but experienced — 1difficulty from getting up form squatting posture

c). Difficulty to squat — 2

d). Difficulty in climbing upstairs — 3

e). Limping gait — 4

f). Can stand on both limbs but with pain — 5

409

g). Can stand without touching the affected limb — 6on the floor

h). Can sit on bed without support but with pain — 7and difficulty

i). Lying in bed with pain affected limb flexed by — 8a supportive pillow

Total numerical value 100

Foot Note: Any abnormalities in Lab. Parameters recorded at the time of admission that maybe considered during the assessment of the progress of the case and also duringfollow up period.

Modern Diagnosis

410

CENTRAL COUNCIL FOR RESEARCH IN AYURVEDA & SIDDHANEW DELHI





2. Address : ..............................................................................................................................

3. Centre :


5. Patient No.

6. Group No

Date of sample taken:

Present Absent (P) (A) (P) (A) (P) (A)

7. Sugar 1 0 1 0 1 0 1 0

8. Albumin 1 0 1 0 1 0 1 0

9. Bile Salt 1 0 1 0 1 0 1 0

10. Bile Pigment 1 0 1 0 1 0 1 0

11. Microscopy 1 0 1 0 1 0 1 0

Investigations at At the time of After 10 days 20 days 30 daysadmission

(1) (2) (3) (4) (5)

411

Stool:

12. Ova 1 0 1 0 1 0 1 0

13. Cyst. 1 0 1 0 1 0 1 0

14. Occult 1 0 1 0 1 0 1 0

Hematological Investigations:

15. Hb%

16. T.L.C.

17. Polymorph

18. Lymphocyte

19. Basophil

20. Monocyte

21. Eosinophil

22. E.S.R.

Biochemistry:

23. Blood Glucose

24. Urea

25. Serum Cholesterol

(P) (A) (P) (A) (P) (A) (P) (A)

26. VDRL 1 0 1 0 1 0 1 0

27. X-ray spine 1 0 1 0 1 0 1 0(AP & Lateral view)

28. Pelvis 1 0 1 0 1 0 1 0

If abnormal, specify abnormalities .........................................................................................

412

BLANK

413

Drug : Study Code:


CLINICAL EVALUATION OF HERBAL PREPARATIONSIN THE MANAGEMENT OF MANODVEGA

(ANXIETY NEUROSIS)


414

BLANK

415

I. BACKGROUND

Life is a conglomerate of body (Shareera), faculties (Indriya), mind (Satva), and soul(Aatma). Any of these cannot be isolated and studied separately. So seers of Ayurveda expressthat the term ‘Shareera’ refers body including five senses and mind.

As mind is a dual faculty (Ubhayendriya) or sensory-motor faculty (J’nana-Karmendriya),it perceives and responds. Even the physical well being is reflected in mind, so is the illness. Thismade the terms happiness (Sukha), and misery (Dukha), synonyms of health and illness. Theinfluence of mind cannot be ruled out in origin, existence or cure of any condition of any disease.When allowed to persist for long time the psychic and somatic disorders get combined with eachother.

Chittodwega/ Manodwega is one of the Manasika Vikara mentioned in Ayurvedicliterature. The symptoms of this disease can be assumed mostly similar with the generalizedanxiety disorder (GAD). GAD is a disorder requires the presence of unrealistic or excessiveanxiety and worry, accompanied by symptoms from three of four categories: (1) motor tension, (2)autonomic hyperactivity, (3) vigilance and scanning, and (4) apprehensive expectation. The anxiousmood must continue for at least a month.

The Ayurvedic principle of synthesis of mind, body and soul to consider man as integratedwhole one, would help to treat mental disorders effectively. Medhya rasayanas and Satvavajayachikitsa are such a measures, which can be utilized for the treatment of Chittodwega/Manodwega1.

In Chittodwega/ Manodwega2, when the mind is afflicted with anxiety, fear, agitation etc.this leads to worry, apprehension, depression, psychological arousal as anger, irritability andultimately lead to disturbance in personal, familial and social harmony.


CLINICAL EVALUATION OF HERBAL PREPARATIONS IN THEMANAGEMENT OF MANODVEGA (ANXIETY NEUROSIS)

References

1. Charaka Samhita with Ayurveda Dipika commentary of Chakrapanidatta, Chaukhambha SanskritSansthan, 5th edition, Varanasi, 2001

2. Sushruta Samhita with Nibandha Sangraha commentary of Dalhana and Nyayachandrikacommentary of Gayadasa, Chaukhambha Orientalia Varanasi, 6th edition, 1997.

3. Harrison: Principals of Internal Medicine Vol. II, 13th edition (International edition).

416

Anxiety disorders3 are among the most prevalent psychiatric condition in the world.Further, studies have persistently shown that they produce inordinate morbidity, utilization of healthcare services, and functional impairment. Recent studies also suggest that chronic anxiety disordermay increase the rate of cardiovascular-related mortality. Hence, clinicians in psychiatry and otherspecialties must make the proper anxiety disorder diagnosis rapidly and initiate treatment.

Ayurveda provides rational means for the treatment of many disorders, which areconsidered to be obstinate and incurable in other systems of medicine.

II. OBJECTIVES

To evaluate the anti-anxiety effect of an ayurvedic compound drug in patients suffering withmanodwega.

To evaluate efficacy & safety of ayurvedic compound drug in manodwega patients

The efficacy of ayurvedic compound drug for six weeks have been studied on manodwegain terms of relieving from the symptoms pridictable through ayurvedic clinical parameters &hamilton’s rating scale for anxiety neurosis.

III. CENTRES



Sample Size : 24 patients in each group (2 groups).

Trial period : 45 Days

Design of the study : Sequential crossover design and double blind method areadopted.

Drug & dosage : The Ayurvedic compound consists of Mandukaparni(Centella asiatica), Yasti (Glycyrrhiza glabra), Jatamamsi(Nardostachys jatamansi) in the ratio of suspended in theKshirabala Thaila. The daily dose of Ayurvedic drug is3gms. / Day in 3 divided doses. Each capsule contains500mgs of drug i.e.Mandukaparni (120mg), Yasti (120mg.)Jatamamsi (240mg.) and ksheerabala taila (3 drops).

The daily dosage of diazepam is 15mg. /day also in threedivided doses. The placebo is plain starch powder.

Duration of the study : 45 days drug therapy with a follow up for 7 days.

417

Study period : 1 year to complete study.

Follow – Up : The follow-up will be carried out after 7 days of treatment.


1. Age between 16-45 years of either sex

2. Presence of cardinal features of manodwega

3. Onset between 8weeks to 2 years

4. Ambulatory and co-operative


1. Age below 16 yrs. and above 45 yrs.

2. Duration of the disease – below 8weeks and above 2years.

3. Exhibiting psychotic symptoms

4. Factors interfering with concentration and communication

5. Hypertension

6. Diabetes

7. Any other systemic diseases


1. If patient does not follows the instructions.

2. Any complication developed during the course of trial.


A detailed clinical and social history is taken. The patients assessed on the basis of clinicalparameters and Hamilton’s anxiety rating scales.

IX. METHOD OF ASSESSMENT OF TREATMENT

1. Clinical Symptomatic Relief

2. Psychological parameters

3. Hamilton’s anxiety rating scale


Data on clinical symptoms and objective tests before and after the treatment will betabulated and analyzed using appropriate statistical tools. However, the data of each case will have

418

to be communicated on completion of trial therapy to the Statistical Officer of CCRAS through e-mail.





B. Data and safety monitoring board: A Data and safety monitoring board (DSMB) atHqrs. will carefully monitor the data and side effects during the period of study and put ina place where by prompt reporting of adverse events occur. The data will be reviewed asevery 20 participants entered the study and administered the trial drugs. The research teamwill report immediately to the PI and Data Monitoring Board if, any life threateningconditions whether they are perceived to be study related or not. The Board decideswhether the adverse effects warrant discontinuation of the study protocol. Protocols will bewritten and approved for the treatment of study related adverse events.


A consolidated amount of Rs.100/- per visit i.e., on the 1st day of recruitment afterscreening, 8th day, 15th day and so on upto 45th day (weekly once).





419







Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “Clinical evaluation of herbal preparations in the management ofManodvega (Anxiety Neurosis)”.





Relationship ___________________________________


420





Chittodwega/ Manodwega is one of the Manasika Vikara mentioned in Ayurvedicliterature. The symptoms of this disease can be assumed mostly similar with the generalizedanxiety disorder (GAD). GAD is a disorder requires the presence of unrealistic or excessiveanxiety and worry, accompanied by symptoms from three of four categories: (1) motor tension, (2)autonomic hyperactivity, (3) vigilance and scanning, and (4) apprehensive expectation. The anxiousmood must continue for at least a month.

The Ayurvedic principle of synthesis of mind, body and soul to consider man as integratedwhole one, would help to treat mental disorders effectively. Medhya rasayanas and Satvavajayachikitsa are such a measures, which can be utilized for the treatment of Chittodwega/Manodwega.

In Chittodwega/ Manodwega, when the mind is afflicted with anxiety, fear, agitation etc. thisleads to worry, apprehension, depression, psychological arousal as anger, irritability and ultimatelylead to disturbance in personal, familial and social harmony.

Anxiety disorders are among the most prevalent psychiatric condition in the world. Further,studies have persistently shown that they produce inordinate morbidity, utilization of health careservices, and functional impairment. Recent studies also suggest that chronic anxiety disorder mayincrease the rate of cardiovascular-related mortality. Hence, clinicians in psychiatry and otherspecialties must make the proper anxiety disorder diagnosis rapidly and initiate treatment.

Ayurveda provides rational means for the treatment of many disorders, which areconsidered to be obstinate and incurable in other systems of medicine.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 45 days.



421



422



CASE REPORT FORM – I SCREENING

BEFORE TREATMENT


1. Name of the patient: .................................................... Age: ................. Sex: ...................

2. Address: ...............................................................................................................................

3. Centre:


5. Patient No.

6. Group No

Yes (1) No (0)


2. Cardinal features of udvega present

3. Onset between 8 weeks and 2 years

4. Ambulatory and co-operative


5. Hypertension

6. Diabetes

7. Any other systemic disease


9. Duration of illness less than 1 month and morethan 2 years

423

10. Exhibiting psychotic symptoms

11. Factors interfering with concentration andcommunication




424



CASE REPORT FORM – II ADMISSION

1. Name of the patient : ...........................................................................................................

2. Address : ..............................................................................................................................


4. Patient No.


6. Centre :


8. Age of Patient (in years)

9. Group No.









12. Total income of the family (in Rs.) ...........................................................


425


Chief Complaints with duration (in days) : Yes (1) No (0)

15. Free floating anxiety

16. Fear

17. Vague aches and pains

18. Panic attacks

19. Difficulty in concentration

20. Psychosomatic symptoms (tick if present)

Depersonalisation

Tremors and tics ____________

Profuse sweating ____________

Dryness of mouth ____________

Throat choking ____________

Chest constriction ____________

Palpitation ____________

(Organicity must be ruled out)




23. Treatment given so far: Ayurvedic medicine 1 Modern medicine 2

Unani 3 Homoeopathy 4

Siddha 5 Mixed 6

24. Factors aggravating the disease / chief complaints_______________________________________________________________________

426

25. Factors relieving main complaints

_______________________________________________________________________

26. History of past illness, having relation with present illness. Yes 1 No 0

If yes, specify _________________________

27. History of previous episodes. Yes 1 No 0

If yes, specify _________________________

Family History, if any Yes (1) No (0)

28. Mental retardation

29. Mental disease

30. Anxiety neurosis

Personal History

31. Diet Veg Non-veg Lacto-ova veg

32. Sleep Good Disturbed Insomnia


34. Bowel habit Regular 1 Constipation 2 Loose 3

35. Addiction Yes 1 No 2

If yes, Specify _______________________________________

36. PRAKRITI :


Vata-kaphaj 4 Vata Pittaj 5 Pitta- Kaphaj 6

Sannipataj 7

427

37. MANAS PRAKRITI :


Sattva Rajas 4 Sattva- Tamas 5 Rajas-Tamas 6

Sama 7

Physical examination

38. Build Lean 1 Medium 2 Heavy 3


40. Body weight (Kg)


42. Blood pressure (diastolic)

43. Body temperature

44. Pulse

45. Respiration


46. Cyanosis

47. Anaemia

48. Jaundice

49. Clubbing of fingers

50. Deformities

51. Lymphadenopathy

Systematic examination Normal Abnormal

52. C.V.S. with chest 0 1

If abnormal, specify abnormalities ____________________________________________

428

53. CNS 0 1


54. Digestive system 0 1


55. Uro-genital system 0 1


Samprapti (Pathogenesis) of the disease according to Ayurvedic concept.

56. Anubandhya Shareerikadosha Vata 1 Pitta 2 Kapha 3

57. Anubandhashareerika Vata 1 Pitta 2 Kapha 3

58. Anubandhya-manasikadosha Rajas 1 Tamas 2

59. Anubandhya-manasikadosha Rajas 1 Tamas 2

60. Ksheena shareerikadosha Vata 1 Pitta 2 Kapha 3

61. Ksheena manasikadosha Rajas 1 Tamas 2

62. Ksheena dhatu (indicate) Rasa 1 Rakta 2 Mamsa 3

Meda 4 Asthi 5 Majja 6

Shkra or Artava 7 Oja 8

63. Dooshya Rasa 1 Rakta 2 Mamsa 3

Meda 4 Asthi 5 Majja 6

Shkra or Artava 7

64. Stages of disease : Sanchaya 1 Prakopa 2 Prasara 3

Sthanasamsraya 4 Vyakti 5

Bheda 6

429

Srotas Pareeksha

65. Pran vaha srota



Abhikshana Swasa (Chyne stroke breathing) 3

Kupit Swasa (Vitiated breathing) 4


66. Udakavaha srota



Talu sosha (Dryness of palate) 3

Kantha sosha (Dryness of throat) 4

Kloma sosha (Excessive thirst) 5

Trishna (Thirst) 6

67. Annavaha srota


Aruchi (Anorexia) 2






Hrillasa (Water brash) 3

430


Tandra (Stupor) 5


Jwara (Fever) 7

Pandu (Anaemia) 8

Avsada (Depression) 9

Klibya (Loss of libibo) 10




Pidika (Boils) 1


Mukha Pak (Stomatitis) 3


Charma roga (Skin disease) 5

Kamala (Jaundice) 6


Arubud (Tumour) 1

Aljee (Phlyctenular conjunctivitis) 2

Gandamalaa (cervical lymphadenitis) 3

Upji (Epiglotis) 4



431


Maladhikya (Excess of excreta) 1



Tandra (Stupor) 4

Dehachikkanta (Greasiness of the skin) 5

Alasya (Lethargy) 6


Adhyasthi (Hypertrophy of bone) 1


Dantshoola (Toothache) 3

Asthi shoola (Bone pain) 4

Kesha, loma, nakha, samshru vikara 5(Any defects of hair, hair follicles, nails and mustaches)

73. Majja_vaha srotas



Moorchh (Syncope) 3


74. Shukra_vaha srotas

Klaivya (Sterility / impotence) 1



Santam Vikriti (Congenital deformity of the children) 4

432

75. Manovaha srotas

Manovibramsha 1

Budhivibramsha 2

Sanjna Vibhramsha 3

Smritivibhramsha 4

Bhaktivibhramsha 5

Sheelavibhramsha 6

Chesta Vibhramsha 7

Acharavibhramsha 8



77. Vandhyatva (Sterility) 2


Bahumutra (Polyuria) 1

Atibadhata (Urination with obstruction) 2

Prakop-mutra (Defective Urination / Difficulty 3in micturition)


Aabhikshna (Constant / repeated urination) 5

Bahulamutrata (Urine with prostatic secretion) 6

Sashool amutrata (Painful micturition) 7


Alpaalpa Pureesha (Scanty defecation) 1

Sashoola Pureesha (Painful defecation) 2

433

Atidrava Pureesha (Diarrhoea) 3

Atigrathita yukta Pureesha (Scybala) 4


Aswedan (Loss of perspiration) 1




Aangaparidaha (Burning sensation in the body) 5

81. Investigations

82. Provisional Diagnosis Final Diagnosis

83. Medical management

84. Principle drug therapy

Drug Dose Vehicle

Diet

85. Duration of treatment

86. Summary of findings

87. Results : Good response 1 Fair response 2

Poor response 3 No response 4

Drop-out 5 LAMA 6

Death 7

Date : Signature of Investigator

434


CLINICAL EVALUATION OF HERBOMINERAL PREPARATIONS IN THEMANAGEMENT OF MANODVEGA (ANXIETY NEUROSIS)

CASE REPORT FORM - III INVESTIGATIONS

Name : ...............................................................................................................................................

Age : ............................... Sex : .................. Date: ......................................................

Investigations Before starting After 45 daystreatment

URINE (24 hour sample)

1. 17 – hydroxyl-cortico steroids

2. 17- keto-steroids

3. Vanillyl mandelic acid (VMA)

4. Routine

HAEMATOLOGICAL INVESTIGATIONS :

5. Hb _________________ gm/dl

6. T.L.C. (in thousand/Cmm)

D.L.C

7. Polymorphs ________________ %

8. Lymphocyte ________________ %

9. Basophil ________________ %

10. Monocyte ________________ %

11. Eosinophill ________________ %

12. E.S.R. 1 hr ________________ mm

2 hr ________________ mm

BIOCHEMISTRY :

13. Blood Glucose (Random) _____________ mg/dl

14. Urea _____________ mg/dl

15. Blood lactic acid estimation if possible

16. S. Creatinine _____________ mg/ dl

17. ECG

435

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436

Blank

METABOLIC DISORDERS

SEC

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438

Blank

439

Drug : Study Code:


PROTOCOL FOR MULTICENTRIC DOUBLE BLINDPLACLINICAL TRIAL OF VYOSHADI GUGGULU IN

THE MANAGEMENT OF OBESITY (MEDOROGA)


440

Blank

441

I. BACKGROUND

Obesity (Medoroga) is a condition in which there is an excessive accumulation of fat in thebody. Framingham study showed that a 20% excess over the desirable body weight clearlyposes risk to health. This disease is a metabolic disease generally occurs in affluent societies. It isassociated with increased mortality by predisposing to the development of important diseases likediabetes, hypertension, atherosclerosis, heart disease, arthritis, infertility etc. and diminishes theefficiency and happiness of those affected.

Because of imbalance between energy intake and expenditure, the excess fat accumulatesin the body. Although no satisfactory etiological classification of obesity is well defined but numberof factors are known to be associated with its development. Obesity is most prevalent in middleage, but it can occur at any stage of life. It is prevalent in high socio-economic group. There arecertain professions in which obesity is common. Familial tendency exists in many cases.Endocrine factors and energy imbalance are also responsible for the obesity. There are certaindrugs which cause obesity like steroids, oral contraceptives, phenothiazine, insulin etc.

The following complications generally occur in this disease viz. - psychological and sexualproblems, mechanical disabilities, osteoarthrosis of knee, hip, lumbar spines, abdominal anddiaphragmatic hernias and varicose veins, exertion dyspnoea, metabolic disorders like non-insulindependent, diabetes mellitus (NIDDM), hyperlipidaemia, gall stones, hyperuricaemia andcardiovascular disorders. Low cardia output increases susceptibility to hypertension and IHD.

The current line of management in modern medicine is not giving satisfactory response inthe treatment of obesity. At this juncture it becomes essential to explore the efficacy of certainAyurvedic drugs in the management of obesity. Guggulu is one of major ingredient of the trial drugof this project, on which many scientific research studies, (experimental and clinical both) havebeen conducted establishing its hypocholestraemic, anti-obesity and anti-atherosclerotic effect.

II. OBJECTIVE

The aim of the present study is to assess the efficacy of Vyoshadi guggul in themanagement of obesity.

III. CENTRES

CCRAS identified centers.


PROTOCOL FOR MULTICENTRIC DOUBLE BLIND PRE-CLINICAL TRIALOF VYOSHADI GUGGULU IN THE MANAGEMENT OF OBESITY

(MEDOROGA)

442


No. of Groups — Two

No. of patients in each group — 60

Sample Size — 120 (60 subjects in each group)


Drug — Vyoshadi Guggulu

Dosage — 1gram (2 capsules of 500 mg. each)two times a day.

Duration — 6 months

Design of the study — Randomised Double blind placebocontrolled study.

Duration of the study — 6 months drug therapy with afollow up for 3 months withoutdrug.

Total period of study — 9 months


1. Age above 25 years and below 60 years of either sex

2. Presence of obesity, i.e., weight is more than 20 % excess of the desirable weightaccording to height, sex and age(according to annexed height and body weight table) OrAge adjusted BMI above 85th percentile (Indian standard)

3. WHR i.e., Waist Hip Circumference ratio >0.95 in males and >0.8 in females


1 Age below 25 years and above 60 years

2. Obesity secondary to or associated with Hypothyroidism, hypertension, Diabetes mellitus,hyperlipidemia or Cushing’s syndrome.

3. Any concomitant serious disorder of the liver, kidneys, heart, lungs or other organs.

4. Pregnancy and Lactation.

5. Person undergoing treatment for any other serious illness.

443


During the course of the trial, if any serious complication develops which requires urgenttreatment with other drugs and therapies, such subjects may be withdrawn from the trial. TheInvestigator shall mention the probable cause of withdrawal.


The full details of history and physical examination of the patients will be recorded as perthe Case Record Form (Forms I & IA). Clinical assessment will be done before drugadministration (0), at the end of 1st month, 3rd month and 6th month during treatment and at theend of 9th month follow up (Form II). The laboratory investigations will be recorded beforedrug administration, at the end of three month, at the end of treatment (6 months) and at the endof follow-up.(9th month) [Form III] .

IX. FOLLOW UP

Follow-up will be carried out for 3 months after completion of treatment.



XI. TRIAL MONITORING

Monitoring unit of CCRAS Headquarters, New Delhi will monitor the progress of the trial.Data analysis will be undertaken by the Monitoring unit at CCRAS headquarter.

XII. ETHICAL REVIEW

A. Institutional Ethical Committee (IEC): The proposal will be placed before EthicalCommittee (IEC) of trial center for getting clearance certificate before the project isinitiated. Patient’s information sheet and informed consent form will be submitted alongwith project proposal for approval by EC. Both will be maintained in duplicate with onecopy given to the patient at the time of entry to the trial.

B. Data and Safety Monitoring Board (DSMB): A Data and safety monitoring board(DSMB) at Hqrs. will carefully monitor the data and side effects during the period ofstudy and put in a place where by prompt reporting of adverse events occur. The data willbe reviewed as every 20 participants entered the study and administered the trial drugs.The research team will report immediately to the PI and Data Monitoring Board if, anylife threatening conditions whether they are perceived to be study related or not. TheBoard decides whether the adverse effects warrant discontinuation of the study protocol.Protocols will be written and approved for the treatment of study related adverse events.

444







445



(MEDOROGA)




Date: _______________ Signature of the investigator ___________

Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the, “Multicentric double blind pre-clinical trial of vyoshadi guggulu in the management of obesity(medoroga).





Relationship ___________________________________


446



(MEDOROGA)



Ayurveda has a very comprehensive approach for the management of Obesity. The presentstudy aims at evaluating selected Ayurvedic formulation for its efficacy in Obesity. You are invitedto participate in this study where you will be provided with a combination of Vyoshadi gugulu inthe dose of 1 gm. (2 capsules of 500mgms each) two times a day. There have been earlier trialstoo showing the efficacy of similar formulation. About 360 persons with Obesity shall be includedin this trial for which 3 big hospitals from different parts of the country are participating in the trial.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 9 months to complete(6months ofmedication and thereafter 3 months of follow up). During this period, you are expected to visit thehospital five times. Six visits shall have to be undertaken one initially when you are included in thetrial, then after one month, after 2 months, after 4th month, after 6th month and after 9th month.


If you are found eligible, you would be put on trial treatment for 6 months. The dailydosage will be 500 mg twice daily. At each visit, you will be supplied with sufficient quantities ofdrugs to last until your next visit.


447



(MEDOROGA)



1. Centre: ______________________________

2. Name of the subject: ______________________________________________________

3. Address : _______________________________________________________________

4. Centre: ______________________________




CRITERIA OF SELECTION Yes (1) No (2)

1. Age between 25-60 years

2. WHR i.e., Waist Hip Circumference ratio >0.95 in males and >0.8 in females

3. Presence of obesity, i.e., weight is more than 20 % excess of the desirable weight (according to annexedheight and body weight table)

Or

Age adjusted BMI above 85th percentile (Indian standard)



5. Endocrine disorders

448


7. Hyper-tension

8. Pregnancy and Lactation

9. Malignancy

10. Athletes or body builders having muscular hypertrophy

11. Cardiac illness




If admitted, Subject’s Serial No. ____________

No. of packets issued: _____________________

Date: ____________ Signature of the Investigator: ________________

449



(MEDOROGA)

CASE REPORT FORM IA – HISTORY

1. Centre: ______________________________

2. Sr. No. of the subject: ____________________________________________________


4. Address : _______________________________________________________________

5. Centre: ______________________________








10. Occupation Desk work 1 Field work 2






12. Income per capita per month (in Rs.) :

450

Chief complaint with duration (if any) in days

Absent (0) Present (1) Duration

13. Polyphagia

14. Polydipsia

15. Excess sweating

16. Excess sleep

17. Body fatigue

18. Loss of libido

19. Palpitation/dyspnoea on exertion

Personal History

20. Diet Veg. 1 Non-veg. 2

21. Sleep Good 1 Disturbed 2 Insomnia 3

22. Emotional stress: No 0 Yes 1

23. Bowel habit: Regular 1 Irregular 2

24. Prakriti: Vataja 1 Pittaja 2 Kaphaja 2

Vata-kaphaja 2 Vatapittaja 2 Pitta-Kaphaja 2

Sannipataja 2

25. Addiction No 0 Yes 1

If yes, Specify__________________________________________


26. Built: Lean 1 Medium 2 Heavy 3


28. Body weight (Kg.) _________________________

451

29. Body height (in cm.) _________________________

30. Skin fold thickness(Triceps) _________________________

31. Blood pressure (Systolic) _________________________

32. Blood pressure (Diastolic) _________________________

33. Pulse _________________________

34. Respiration _________________________


35. Cyanosis

36. Anaemia

37. Jaundice

38. Lymphadenopathy

SYSTEMIC EXAMINATION Absent (0) Present (1)

39. C.V.S. (with Chest)

If abnormal, specify abnormalities_________________________________

40. C.N.S.

If abnormal, specify abnormalities_________________________________


If abnormal, specify abnormalities___________________________________



43. Respiratory System


452

Samprapti (pathogenesis) of the disease according to Ayurvedic concept

44. Dosa Vata Pitta Kapha

Anubandhya dosha

Anubandh dosha

Avaraka dosha

Ksheen dosha

45. Dushya (Involved): Rasa Rakta Mamsa

Meda Asthi Majja

Shukra Ojas

Srotas Pariksha





Tandra (Stupor) 4


Alasya (Lethargy) 6

47. Garbhapata (Abortion) Absent (0) Present (1)

48. Santana vikriti Absent (0) Present (1)(Congenital deformity in the children)


453



(MEDOROGA)

CASE REPORT FORM II – CLINICAL AND ANTHROPOMATRIC ASSESSMENT

(0, 1, 3, 6, 9th months)

1. Centre: ______________________________



4. Address : _______________________________________________________________

5. Centre: ______________________________






10. Polyphagia

11. Polydipsia

12. Excess sweating

13. Excess sleep

14. Body fatigue

15. Loss of libido

16. Palpitation/dyspnoea on exertion

454

Anthropometric assessment

17. Body weight (Kg.) _________________________

18. Skin fold thickness(Triceps) _________________________


Continuing (1)

Drop out (2) Reason: _____________________________

Died (3) Cause: _______________________________


455


MULTICENTRIC DOUBLE BLIND CLINICAL TRIAL OF VYOSHADIGUGGULU IN THE MANAGEMENT OF OBESITY (MEDOROGA)

(0, 3rd , 6th AND 9th MONTH)

FORM III – LABORATORY INVESTIGATIONS

1. Centre: ______________________________



4. Address : _______________________________________________________________

5. Centre: ______________________________








Routine ____________ Microscopic____________

Ova/Cyst ___________ Occult Blood____________

12. TC (Cells/Cmm.)_____________________

13. DC: P (%) _______ L (%) _______ E (%) _______ M (%) _______ B (%) ________

14. Hb (g/dl) _________

15. ESR (1st hour mm) __________

456

16. PCV (%) _______________

17. Blood Sugar – PP (mg./dl) _______________

18. S. Cholesterol (mg./dl) _______________

19. HDL(mg./dl) _______________

20. LDL (mg./dl) _______________


22. B. Urea (mg./dl) _______________


24. Uric acid (mg./dl) _______________


26. Albumin (gm./dl) _______________

27. Globulin (gm./dl) _______________

28. A/G Ratio _______________

29. Acid Phosphates (KA units) _______________

30. Alk. Phosphates (KA units) _______________

31. E.C.G: [ 0 Month only]

32. X-ray Chest: [ 0 Month only ] _____________________________________________

33. T3: _________ T4 : __________ TSH: ___________

34. Any other Remarks _____________________________________________

Date: _____________ Signature of the Investigator: ______________________

457

Drug : Study Code:


RANDOMISED DOUBLE BLIND CONTROLLEDCLINICAL TRIAL OF AYUSH-DIAB IN CONTROLLING

BLOOD SUGAR LEVEL IN Type 2 DIABETESMELLITUS


458

Blank

459

I. BACKGROUND

Diabetes is a metabolic disorder; a comparable condition of Madhumeha specifically anabnormality in the way of the body utilizes glucose, due to an absolute or relative deficiency of thehormone insulin or resistance by the body tissues to the action of insulin.

Conventional modern medicine provides a number of drug of choice for controlling theblood sugar level in the patients of diabetes mellitus type-2. However, with the prolongedtreatment doses of the drugs often needs to be increased to control the blood sugar level and atime comes when patient has to be switched over to insulin. Such patients become cases of insulindependent diabetes mellitus. With a view to help the suffering community there is a need to find asafer drug, which can be used to control the blood sugar level and such drug can be used safetyfor longer periods.Ayurvedic classics provide references on herbal and herbo-mineral preparationswhich can be safely used in controlling the blood sugar level in the patients of diabetes mellitus.1

II. OBJECTIVE

To study the effect of Ayurvedic formulation in controlling blood sugar level of the patientssuffering with Type-2 Diabetes mellitus.

III. CENTRE

Identified Centres of CCRAS


RANDOMISED DOUBLE BLINDCONTROLLED CLINICAL TRIAL OF AYUSH-DIAB IN CONTROLLING BLOOD SUGAR LEVEL IN Type 2 DIABETES

MELLITUS

References

1. Harrison’s Principle of Internal Medicine 15th Edition Page 2109-2135.

2. The Expert Committee on the Diagnosis and classification of Diabetes Mellitus : Report of theExpert Committee on Diagnosis Classification of Diabetes Mellitus, Diabetic care 1997;207:1183-97.

3. Siddharth N Shah, Asshit Shah, API Text Book of Medicine 5th Edition Page-1460.

4. Vaisajya Ratnawali, Saptam Sanskaran 2040 Page 812.

460


Sample Size-100

Total Number of group-Two

Total number of patients in each group-50

Level of study-OPD

Treatment:

A. Dietary regimen: Patient will be advised to restrict their dietary schedule and dolight exercises (like brisk walking for two kms. per day, swimming, jogging etc.during treatment).

B. Trial drug:

1. Ayush-DIAB 500 mg dragees BD with water half hrs before meals (CapsuleAyush-DIAB contained extracts of Meshashringi (leaves) one part+ Amra BeejaMajja one part + Karvelaka Beeja one part + Jambu Beeja one part + Silajeetaone part) for six months.

Diet: -Patients will be advised to take their diet as described in Patient information sheetand do brisk walking/jogging or light exercise for half hour daily..

2. Standard control: Glimepiride 1mg OD ½ hour before meal.

Duration of the study: Six months (total duration of the study 2 years)

Duration of medication - Six months

Total duration of study – 2 years



2. If yes in any of the three

Blood sugar – Fasting > 126 and =< 200 mg/dl or

PP > 200 mg/dl and <= 350 mg/dl or

Glycated haemoglobin > 7% and <10%

3. Recently diagnosed (< 6 Month) cases of Type-2 Diabetes mellitus not taking any antiDiabetic drug.

461



If yes in any of the three

Blood sugar – Fasting =< 126 and > than 200 mg/dl or

PP=< 200 mg/dl >350 mg/dl or

Glycated haemoglobin<=7% and =>10%

2. Malignant and accelerated hypertensive

3. CVS disorder (CAD)

4. Pregnant woman and planning to be pregnant within six months

5. Lactating mother

6. Secondary Diabetes mellitus

7. Patient under going regular treatment for Diabetes or any other severe illness

8. CNS disorder e.g. encephalopathy


The investigator shall withdraw the patients from the study if

1. Fasting blood sugar rises to >200 mg. /dl. Or post prandial blood sugar level increasesto>350 mg./dl and are not controllable within fifteen days.

2. Any serious complication develops which requires urgent treatment with any other drug/therapy?

The investigator will mention the probable cause of withdrawal and provide possiblemedical treatment to manage the illness.


The full details of history and physical examination of the patients will be recorded as per theproformae (Forms I & IA). Clinical and physiological assessment will be done before drugadministration and after every two weeks. The laboratory investigations will be recorded before drugadministration, after every two weeks (blood Sugar only) and at the end of treatment (Form-III)


If during treatment or after treatment fasting Blood sugar becomes<126 mg. /dl. and postprandial Blood sugar< 200mg./dl. and HbA1c < 7% it will be treated as successful outcome ofthe treatment.

462


Data on Fasting/Post prandial blood sugar and HbA1c will be analyzed using appropriatestatistical methods.


The progress of the trial will be monitored by CCRAS Hqrs. New Delhi consisting of oneexpert each of allopathy and Ayurveda besides one outside expert. Data analysis will beundertaken at the Monitoring Unit CCRAS Hqrs. New Delhi

XII. ETHICAL REVIEW


B. Data and safety monitoring board: A Data and safety monitoring board (DSMB) atHqrs. will carefully monitor the data and side effects during the period of study and put ina place where by prompt reporting of adverse events occur. The data will be reviewed asevery 20 participants entered the study and administered the trial drugs. The researchteam will report immediately to the PI and Data Monitoring Board if, any life threateningconditions whether they are perceived to be study related or not. The Board decideswhether the adverse effects warrant discontinuation of the study protocol. Protocols will bewritten and approved for the treatment of study related adverse events.





463


RANDOMISED DOUBLE BLIND CONTROLLED CLINICAL TRIAL OFAYUSH-DIAB IN CONTROLLING BLOOD SUGAR LEVEL IN Type 2

DIABETES MELLITUS

CONSENT FORM



Date: _______________ Signature of the Investigator: ___________

Name of Investigator: ________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on Randomized Controlled Clinical Trial of Ayush-DIAB Capsules in theControlling Blood Sugar Level in Type 2 Diabetes mellitus.





Relationship ___________________________________


464


RANDOMISED DOUBLE BLIND CONTROLLED CLINICAL TRIAL OFAYUSH-DIAB IN CONTROLLING BLOOD SUGAR LEVEL IN Type 2

DIABETES MELLITUS



Research is going on to find a suitable natural product for the treatment of Type-2Diabetes mellitus. You are invited to participate in such a study in which you will receive eitherAyurvedic trial drugs or control drug for 24 weeks.

The aim of the present study is to assess the anti-diabetic effect of these drugs in themanagement of Type 2 Diabetes mellitus patients.

Total 100 patients from this and other hospitals will be taking part in this study.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately six months to complete. After thisperiod, you are expected to visit the hospital every fortnight. The interval between the first andsecond visit will be around 15 days.

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination. ECG, Blood and urine samples will also be taken. This is to make sure thatyou are eligible for the study.

One week later, at your second visit, if you are eligible, you would be put on trial treatmentfor 24 weeks. You may receive either trial drug or control drug for 24 weeks. You should followlife style modifications (Diets Advice, Exercise) as given along with information Sheet.

From the first visit onwards, you will be required to fast overnight before attending eachvisit. Blood and urine samples will be taken at every visit. At each visit, you will be supplied withsufficient quantity of drug to last until your next visit.

What happens at the end of the study?

The trial treatment will be stopped at the end of 24 weeks. You will be put back on anappropriate treatment available in the market.

465

Are there any risks?

Both trial and control drugs may cause hypoglycemia (very low blood sugar) in somecases. The symptoms of hypoglycemia are sweating, drowsiness, nausea, confusion and in-coordination. In case of such symptoms, you should immediately take sugar, glucose/biscuits andmilk/fresh lime juice/orange juice with sugar and report to the doctor.

What are the alternatives?

Your doctor will be pleased to explain to you the available alternative treatment to controlyour blood sugar?

When you leave can the study?

Your participation in the study is entirely voluntary. You can choose to leave the study atany time. Your decision to leave the study will not affect your medical care or relationship withyour doctor.

Your doctor may decided that you should not continue in the study if, a) your blood sugarbecomes very high or very low, b) you start on insulin or other medication that affect blood sugar,c) you take part in any other trial.

What is the cost of the study?

All medication and tests to be done during the study will be free of charge.

If you do not want to participate, you are free to do so. It will not affect your medicalcare or relationship with your doctor in any way.

What happens now if you decided to take part?

You will asked to sign a consent form saying that you have been given information aboutthe study and you voluntarily agree to take part.

It is important to follow all instruction given by your doctor or doctor’s assistant carefully.

DIET REGIMEN:

To take 25 cal/kg per day (Moderate work)

Protein 0.8 gm/kg per day

Total Fat < 30% of calories (Saturated fat < 10% polyunsaturated fat < 10% of calories)

Cholesterol < 300 mg per day

Dietary fibre 50 gm per day (atleast)

Common salt < 5 gm. per day

466

Saturated fat & cholesterol are found in e.g. Ghee, Vanaspati, Dalda, Palm, Coconut oil.These contain highly saturated fat. Patient should be advised to take less saturated fat andcholesterol.

Poly unsaturated fat take Sun flower oil, Soyabene oil, Olive oil which containedunsaturated fat should be taken 3 small tea spoonful / day.

Milk : Three cup daily double tone

Whole Cereal: 90 gm daily. [old samarice, kodo, java, wheat with husk]

Vegetable : 250 gm daily [padwal, karaila, methi, pumpkin, brinjal, beans]

Dal : 400 ml. daily [Moong, Masoor, Kulthi, Arhar, Garam]

Fruits : 200 gm. Daily [Apple,Guava & Pappaya]

Spices : [Ginger,coriander,cardamom]

DO’NT

To avoid smoking.

To avoid Fasting.

To avoid sweets, honey, sugar, jaggery, cold drinks, fruit juice, avoids fruits e.g. Mango,Sharifa, Grapes, Chiku, Banana, Khajur, potato,turnip & beetroot


467



MELLITUS


1. Centre: ______________________________


3. Sr. No. of the Subject : ____________________________________________________

4. Address : _______________________________________________________________







Blood sugar – Fasting > 26 and =< 200 mg/dl or

PP > 200 mg/dl and<= 350 mg/dl or

Glycated haemoglobin>7% and <10%

3. Recently diagnosed (< 6 Months)

Cases of Type-2 Diabetes mellitus

Not taking any hypoglycemic drug or insulin.

CRITERIA FOR EXCLUSION Yes (1) No (0))


468


Blood sugar – Fasting =< 126 and > than 200 or

PP=< 200 mg/dl >350 mg/dl or

Glycated haemoglobin<=7% and =>10%

6. Malignant and accelerated hypertensive

7. CVS disorder (CAD)

8. Pregnant woman or the women planning to be pregnant in next six months

9. Lactating mothers

10. Secondary Diabetes mellitus

11. Patient under going regular treatment for Diabetes or for any other severe illness

12. CNS disorder e.g. encephalopathy

A patient is eligible for admission

If ‘Yes’ to S.No.1 – 3 & ‘No’ to 4 – 12

If admitted:

Sl. No. of the subject ____________

No. of packets issued____________

Date:____________ Signature of the Investigator _____________

469



MELLITUS


1. Centre: ______________________________




5. Address : _______________________________________________________________













12. Religion : Hindu 1 Muslim 2 Sikh 3

Christian 4 Parsi 5

470



13. Polyuria (Excessive Urine)

14. Polyphagia (Excessive Hunger)

15. Polydipsia (Excessive Thirst)

16. Exhaustion/Tiredness

17. Loss of body weight

18. Body ache

19. Giddiness

20. Polyneuritis(Numbness / Tingling)

21. Visual disturbance

22. Others

If Yes specify: _____________________________________

Personal History

23. Diet Veg. 1 Non-veg. 2 Lecto-veg 3

24. Presence of anxiety No 0 Yes 1

25. Constipation No 0 Yes 1

Addiction


If yes specify: (a) Quantity [packs]: ________________

(b) Total Duration in year’s ________________


If yes specify: (a) Quantity: ________________


471


If yes specify: (a) Quantity (in ml/day): ________________


29. Any other(specify) _____________________

30. Prakriti: Vata 1 Pitta 2 Kapha 3

Vata-kaphaj 4 Vata-pittaja 5 Pitta-Kaphaja 6

Sannipataj 7


31. Height (cm) ____________

32. Weight (kg) ____________

33. Pulse (per min) ____________

34. Blood Pressure (in sitting position)

Systolic_________________(mm Hg)

Diastolic ________________(mm Hg)

35. Body temperature (o F) _____________


37. Signs of dehydration and oedema, if any____________________

SYSTEMIC EXAMINATION Absent (0) Present (1)

38. CVS

If abnormal, details _______________________________________________________

39. CNS


472







Date: ____________________ Signature of Investigator ___________________

473



MELLITUS

CASE REPORT FORM III - CLINICAL & PHYSIOLOGICAL ASSESSMENT

[Before Treatment & Fortnightly During Treatment]

1. Centre: ______________________________




5. Address : _______________________________________________________________





Absent (0) Present (1) Duration(in days)

9. Polyuria (Excessive Urine)

10. Polyphagia (Excessive Hunger)

11. Polydipsia (Excessive Thirst)

12. Exhaustion/Tiredness

13. Bodyache

14. Giddiness

15. Polyneuritis (Numbness / Tingling)

474

16. Visual disturbance

17. Others

If Yes, specify: ___________________________________________________________

Physiological Assessment

18. Weight (in Kgs.) ______________

19. Blood Pressure (in sitting position)

Systolic_________________ (mm Hg)

Diastolic ________________ (mm Hg)


475



MELLITUS

CASE REPORT FORM IV- LABORATORY INVESTIGATION

1. Centre: ______________________________


3. Sr. No. of the subject: _____________________________________________________

4. Name of the subject: _______________________________________________________

5. Address : _______________________________________________________________




Urine Examination

Routine

9. Sugar ____________

10. Albumin ____________

11. Deposits ____________

Microscopic

12. Pus cell ____________(hpf)

13. RBC ____________(hpf)

14. Cast ____________(hpf)

Stool examination

15. Routine ____________

476

Microscopic

16. Ova ____________

17. Cyst ____________

18. Occult Blood__________

Blood

19. TC (Cells/Cmm.): ____________

20. DC: P(%)_____ L(%)_____ E(%)_____ M(%)_____ B(%)_____

21. Hb (g/dl) ____________

22. (1st hour.) ____________

23. Blood Sugar- Fasting/PP (mg./dl)____________/____________

24. Glycosylated) HbA1c (to be done before treatmentafter three months and end of treatment)

25. Blood Urea (mg. /dl) ____________

26. S.Creatinine (mg./dl) ____________

27. Uric acid (mg./dl) ____________

LIPID PROFILE

28. Serum total Cholesterol (mg./dl) ____________

29. S. Triglycerides (mg./dl) ____________

30. HDL (mg./dl) ____________

31. LDL (mg./dl) ____________

32. VLDL (mg/dl) ____________

LIVER FUNCTION TEST

Serum Bilirubin

33. Total (mg/dl) ____________

477

34. Direct (mg/dl) ____________

35. SGOT (IU/L) ____________

36. SGPT (IU/L) ____________

37. Alk.Phosphatase (KA units) ____________

38. Total proteins (gm./dl) ____________

39. Albumin (gm./dl) ____________

40. Globulin (gm./dl) ____________

41. A/G Ratio ____________

Serum Electrolytes

42. Sodium(mEq/L) ____________

43. Potasium(mEq/L) ____________

Sl.No.9 – 43 will be done before and after treatment except Sl.No. 23 (Blood Sugar) whichwill be done before treatment and fortnightly during treatment period. HbA1c will be repeatedafter three months also.

Date: ______________ Signature of Investigator__________________________

478

Blank

EYE DISORDERS

SEC

TIO

N - V

II

480

Blank

481

Drug : Study Code:


CLINICAL EVALUATION OF AYUSH-CT DROPS ANDAYUSH-CT CAPSULE IN IMPROVING THE QUALITY

OF VISION AND PREVENTION OF PROGRESS INSENILE IMMATURE CATARACT (LINGANASA)


482

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483

I. BACKGROUND

Senile cataract (Linganasa1) is a disease of common occurrence in all geographical areasand in all races. The incidence, however, is distinctly more in tropical countries. The two factorspeculiar to tropical circumstances and responsible for this high incidence are higher concentrationof actinic rays in tropical sunlight, and the nutritional deficiency factors so significant in these areas.It can be generally stated that in developing tropical countries, the age of 50 years and above isconsidered a cataractogenous age and the degree of incidence increases as the age advances. Itis safe to assume that 60% people develop cataract by the age of 60 years. 70% by the age of70 years, 80% by 80 years and 90% by 90 years of age. It was estimated that 55% of total orpartial blindness was due to cataract in some stage of its formation. Of these, the incidence inrural areas was 70% and in Urban areas 30%. Similarly, the incidence in males was 64.4% ascompared to 35.6% in females. It is rare in persons under 50 and these disturbances occur in (a)impaired semi permeability of the capsule, (b) increased insoluble proteins, and (c) less effectiveauto-oxidative system.

The current lines of management include various surgical methods. There is no definitemedical treatment for this condition in the patients where surgical treatment is not suitable (likeuncontrolled diabetes, cardiac disorders and so on.) Ayurvedic literatures have recorded manysingle drugs and compound formulations for the treatment of Linganasa/Timira. (Cataract) .Drugslike Punarnava, Amalaki, Palasha etc. possess various pharmacological actions like Chakshushaya(Improves visual acuity), Timira hara (Effective managing various disorders of vision) besides itsRasayana action that prevents free radical damage i.e. anti-oxidant effect1.

II. OBJECTIVE

To evaluate the therapeutic efficacy of Ayush-CT Drops and Ayush-CT Capsule Inimproving the quality of vision and Prevention of progress in senile immature cataract


CLINICAL EVALUATION OF AYUSH-CT DROPS AND AYUSH-CT CAPSULEIN IMPROVING THE QUALITY OF VISION AND PREVENTION OF

PROGRESS IN SENILE IMMATURE CATARACT (LINGANASA)

References

1. Ambika Dutta Sashtri (1989) Susruta Samhita (text with Hindi commentary) Uttara Sthana, VIIthEdition Chaukhamba Sanskrit Series Office, Varanasi.

2. Actions & uses of indigenous ophthalmic drugs, Chaukhamba Sanskrit Pratisthan, New Delhi

484

III. CENTRE



Sample size : 50 cases


1. Ayush-CT Drops {Distillate (Ark) of equal parts of Punarnava andPalashamoola} two drops three times a day and Ayush-CT Capsule (Extract ofequal parts of Punarnava and Amalaki) 500mg. two capsules BD for 4months

2. Placebo- Distilled water two drops three times a day and glucose capsules 500mg.two capsules BD for 4 months

Design of the study : Double blind Randomized controlled trial

Duration : Four months drug therapy with a follow up for two monthswithout drug.

Period of Study : Six months (Four months drug therapy and two monthsfollow-up) for each case. Total duration will be two yearsto complete the trial.

Follow – Up : One follow-up will be carried out after two months of thecompletion of treatment.


1. Age above 50 years and up to to 80 years

2. Both the sex

3. Immature cataract (confirmed by ophthalmoscopy, retinoscopy/iris shadow presence)

With any one or both of the symptoms

• Disturbance in vision (diplopia,polyopia,holes etc)

• Diminished visual acuity


1. Age below 50and above80 years

2. Mature cataract

3. Sluggish pupil reaction

485

4. Hypertension


6. Glaucoma

7. Any other illness causing notable visual morbidity



During the course of the trial treatment, if any serious condition develops/ symptomsaggravates, which requires urgent treatment, such subjects may be withdrawn from the trial andmanaged by the Principal Investigator accordingly.


The full details of history and physical examination of the patients will be recorded as perthe proforma (Forms I & IA). Clinical assessment will be done during treatment (Form II). Thelaboratory investigations will be carried out before and after the treatment.


Data on disturbance in vision and diminished visual acuity will be analyzed usingappropriate statistical methods.

Improvement in visual acuity (Using near vision and distance vision chart-Snellen’s testtype) and disappearance of symptoms of disturbances in vision (Clinical assessment) will beconsidered as significant, besides status of cataract examined through ophthalmoscopy, retinoscopyand Iris shadow tests.

X. TRIAL MONITORING AND DATA ANALYSIS


XI. ETHICAL REVIEW


B. Data and safety monitoring board: A Data and safety monitoring board (DSMB) atHqrs. will carefully monitor the data and side effects during the period of study and put ina place where by prompt reporting of adverse events occur. The data will be reviewed as

486

every 20 participants entered the study and administered the trial drugs. The research teamwill report immediately to the PI and Data Monitoring Board if, any life threateningconditions whether they are perceived to be study related or not. The Board decideswhether the adverse effects warrant discontinuation of the study protocol. Protocols will bewritten and approved for the treatment of study related adverse events.


A consolidated amount of Rs.……. /- per visit will be paid to subjectsselected.





487




CONSENT FORM




Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the trial on “Clinical Evaluation Of Ayush-CT Drops And Ayush-CT Capsule In improving thequality of vision and Prevention Of Progress in senile immature cataract”





Relationship ___________________________________


488






Senile cataract (Linganasa) is a disease of common occurrence in all geographical areasand in all races. The incidence, however, is distinctly more in tropical countries. The two factorspeculiar to tropical circumstances and responsible for this high incidence are higher concentrationof actinic rays in tropical sunlight, and the nutritional deficiency factors so significant in these areas.It can be generally stated that in developing tropical countries, the age of 50 years and above isconsidered a cataractogenous age and the degree of incidence increases as the age advances. Itis safe to assume that 60% people develop cataract by the age of 60 years. 70% by the age of70 years, 80% by 80 years and 90% by 90 years of age.

The current lines of management include various surgical methods. There is no definitemedical treatment for this condition in the patients where surgical treatment is not suitable likeuncontrolled diabetes, cardiac disorders and so on. Ayurvedic literatures have recorded manysingle drugs and compound formulations for the treatment of Linganasa/Timira. Drugs likePunarnava, Amalaki, Palasha etc. possess various pharmacological actions like Chakshushaya(Improves visual acuity), Timira hara (Effective in managing various disorders of vision) besides itsRasayana effects that prevents free radical damage i.e. anti-oxidant effect.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately six months to complete ( four monthsfor treatment and another two months for follow-up study). During this period, you are expectedto visit the hospital six times, once in a month during drug treatment and once at the end of 6th

month during the follow up.


If you are found eligible, you would be put on trial treatment OR placebo therapyfor four months. Daily dose of oral treatment consist of two 500-mg. capsules twice a dayalong with eye drops two drops three times a day for four months

489

At each visit, you will be supplied with sufficient quantities of drugs to last untilyour next visit. If any adverse reactions like skin allergy, nausea, vomiting andpalpitation/tremor etc., noticed during the treatment period, this should be informed to thePrinciple Investigator.


490





BEFORE TREATMENT


1. Centre: ______________________________



4. Sr. No. of the Subject : ____________________________________________________

5. Address : _______________________________________________________________



1. Age above 50 years up to to 80 years

2. Both the sex

3. Immature cataract (confirmed by ophthalmoscopy, retinoscopy/iris shadow presence) With any one orboth of the symptoms

4. Disturbance in vision (diplopia,polyopia, holes etc/ Diminished visual acuity)


5. Age below 50and above 80 years

6. Mature cataract.

7. Sluggish pupil reaction

491


9. Glaucoma

10. Hypertension

11. Person undergoing treatment for

12. Any other serious illness

If yes, specify: __________________________________________________

13. Any other illness causing notable visual morbidity

If yes, specify: __________________________________________________


If ‘YES’ to 1 – 4 and ‘NO’ to 5 – 13

If admitted, subject serial No: _________

No. of packets issued: _______________

Date: ____________ Signature of Investigator: _________________________

492




CASE REPORT FORM II- HISTORY


1. Centre: ______________________________



4. Address : _______________________________________________________________












Chief complaint with duration (in month) Yes (1) No (2)

10. Disturbance in vision

If Yes, duration in months _________________

493

11. Diplopia

If yes, duration in months __________________

12. Polyopia

If yes, duration in months _________________

13. Holes

If yes, duration in months _________________

14. Any other visual disturbances

If yes, (specify): __________________

Duration in months: _______________

15. Diminished visual acuity

If yes, details* &duration in months _________________

Visual acuity (Snellen’s test type)

Distant vision:

16. Right Eye: ___________

17. Left Eye: ___________

18. Both Eyes: ___________

Near vision:

19. Right Eye ___________

20. Left Eye ___________

21. Both Eyes ___________

22. History of cataract in family Yes (1) No (0)

If Yes, relation with patient _________________

494

23. Prakriti Vata 1 Pitta 2 Kapha 3


Sannipataja 7

EXAMINATION OF THE EYE

24. General examination Normal 1 Abnormal 2

If abnormal, specify abnormalities ____________________________________

Lens (Medoashrita patala)(ophthalmoscopy)

25. Colour: Gray Brown Transparent

26. Opacity: Central Peripheral Total

27. Position Normal 1 Displaced 2

28. Iris shadow Present 1 Absent 2

Vitreous Present (1) Absent (2)

29. Degenerative changes

30. Opacity

Pupil (Dristi mandal) Normal (1) Abnormal (2)

31. Size

Reaction Present (1) Absent (2)

32. Direct

33. Consensual

34. Retina (Asthiashrita patala)

If abnormal, specify ___________


Distant vision:

495

35. Right Eye ___________

36. Left Eye ___________

37. Both Eyes___________

Near vision:

38. Right Eye ___________

39. Left Eye ___________

40. Both Eyes___________

Glasses (Correction)

Right Eye Left Eye

Vision Sph Cyl Axis Vision Sph Cyl Axis Vision

41. NV

42. DV

Tonometry (Schitoz’s)

Intraocular pressure*

43. RE ________ mm/Hg

44. LE ________ mmHg

* 6-21 Normal

Date: ____________ Signature of Investigator: _________________________

496





(0, end of 1st, 2nd, 3rd, 4th, 5th & 6th month)


1. Centre: ______________________________



4. Address : _______________________________________________________________

5. Gender Male Female



7. Disturbance in vision

8. Diplopia

9. Polyopia

10. Holes

11. Any other visual disturbances (specify)

If Present, Specify___________________________


Distant vision:

12. Right Eye ___________

13. Left Eye ___________

497

14. Both Eyes ___________

Near vision:

15. Right Eye ___________

16. Left Eye ___________

17. Both Eyes ___________

18. Adverse reaction: Yes (0) No (1)

If yes, details: _______________________


Continuing (1)

Drop out (2) Reason:_____________________________

Date: ______________ Signature of Investigator: ___________________

498




CASE REPORT FORM IV – LABORATORY INVESTIGATIONS ANDPHYSIOLOGICAL PARAMETERS

(Before the treatment)

1. Centre: ______________________________



4. Address : _______________________________________________________________




8. Urine Sugar _____________________________________________________________

9. Blood Sugar - PP (mg./dl)

Date : __________________ Signature if Investigator : ___________________

499

Drug : Study Code:


CLINICAL EVALUATION OF THE EFFECT OFTARPANA AYUSH-DE EYE DROPS, AYUSH-DE

CAPSULES IN THE MANAGEMENT OF DRY EYESYNDROME (SHUSHKAKSHIPAKA/PARISHUSKHA

NETRA)


500

Blank

501

I. BACKGROUND

In certain conditions, there is insufficiency of lubrication of eye and the conjunctivabecomes dry. Deficiency in any components of tear film, results in dryness of the eye, due to theappearance of dry spots on the corneal and conjunctival epithelium. Sushruta consideredshushkakshipaka as an individual disease and classified under sarvagata netra rogas. Even thoughthere is no separate entity such as Parishushka netra in classics, authors of different textsmentioned the above condition while describing the therapeutic procedure adapted for themanagement of eye disease. Conditions like Ativishushka netra, Ashrusrava rahita netra,Asnigdha netra are mentioned in Nibandha samgraha (one of the commentaries on SushrutaSamhita.)

There are many conditions which cause dryness of the eyes. Hypofunction of lacrimalglands (eg. sjogren’s syndrome, sarcoidosis, lymphoma, leukemia amyloidosis.), mucin deficiency(e.g. vitamin A deficiency), conjunctival scarring, (e.g. trachoma, Stevans Johnson syndrome,pemphigold, chemical burns, chronic bacterial or viral conjunctivitis, irradiation and miscellaneouscauses such as mumps, deficient blinking etc.).

(Kapha is responsible for sanigdhatwa (oiliness) sthiratwa (structrual and functional integrityof body systems) by means of its qualities like gurutwa and shitatwa.) Tarpaka kapha, one of thefive varieties of Kapha, situated in siras is responsible for the integrity of sense organs(akshitarpana). According to Dalhana, the term aksha refers to sense organs like netra. Collectivefunction tear film components can be correlated with the function of the tarpakakapha.

Clinical studies conducted with topical and internal use of Ghrita prepared with the Haridraand Daruharidra has shown significant improvement in subjective parameters like Dryness,Redness, Photophobia etc. Pharmacological actions such as chaksushya (conducive to vision),netrya (conducive to eye), netra ruja hara (analgesic ophthalmic action) are attributed to haridra,daruharidra and ghrita from which the formulation under taken for the study was prepared. Theresponse obtained after the clinical study could be well understood with the abovepharmacological actions ascribed to various ingredients 1&2


CLINICAL EVALUATION OF THE EFFECT OF TARPANA AYUSH-DE EYEDROPS, AYUSH-DE CAPSULES IN THE MANAGEMENT OF DRY EYE

SYNDROME (SHUSHKAKSHIPAKA / PARISHUSHKA NETRA)

References

1. Dry Eye Syndrome and its management – A clinical study, JRAS, Vol.XXII, No.1-2, (2001)pp.17-24.

2. Actions & uses of indigenous ophthalmic drugs, Chaukhamba Sanskrit Pratisthan, New Delhi.

3. Sushruta Uttarasthana Chapter 9/18-22

502

II. OBJECTIVE

To evaluate the effect of Ayush-DE drops and Akshi tarpana in dry eye syndrome(shushkakshipaka / parishuskha netra)

III. CENTRE



No. of groups : Four groups

No of patients in each group : 25

Type of Study : Open

Level of Study : OPD/IPD

Period of Study : 4 months (3 months treatment and onemonth follow up Study with DistilledWater)

Treatment:

Group-I

1. Akshi Tarpana with Ayush-DE Ghrita {prepared with equal parts of Yashtimadhu(Glycerrhiza glabra)} for five days.

2. Installation of Ayush-DE drops {Yashtimadhu (Glycirrhiza glabra)} three dropsthree times a day for three months.

Group-II

Installation of Ayush-DE drops {prepared with Yashtimadhu (Glycirrhiza glabra)} threedrops three times a day for three months.

Group-III

Artificial tears for three months (conventional)

Group IV

Autoserum (optional)

Procedure of tarpana

Local application of tila taila around the eye orbit followed by mild sudation will be givenas purvakarma. Concentric boundary should be made around each orbit with paste of mashachoorna (Powder of Phaseolus mungo). 20 ml of lukewarm medicated ghee should be filled andallowed to retain in the boundary for twenty minutes. After the prescribed period, ghrita will beremoved with cotton pads followed by removal of the boundary.

503


1. Dryness of the Eye with or without

a) Sandy and scratchy feeling

b) Pain / pricking sensation

c) Photophobia

d) Mild reddness/ Mild blepharitis

e) Less flow of tears even when exposed to irritant odour and fumes

f) Foreign body sensation

g) Mild reddness


3. Tear film break-up time less than 10 seconds

4. Rose Bengal staining showing devitalized epithelium of conjunctiva and mucus plaques onthe cornea.

5. Schimers tests positive < 10 mm (exact measurement)

6. Chronicity upto six months.


1. Age below 20 years above 40 years

2. Chronicity above 6 months.

3. Corneal ulcer

4. Degenerative condition of conjunctiva

5. Extra ocular and intra ocular infections

6. Contact Lens users

7. Systemic disease causing Dry Eye Syndrome (Physicians remarks)


During the course of the trial treatment, if any serious condition develops/ symptomsaggravate, which requires urgent treatment, such subjects may be withdrawn from the trial andmanaged by the Principal Investigator accordingly.


The full details of history including any associated diseases and physical examination of thepatients will be recorded as per the Proforma (Forms I & II). Clinical assessment will be done

504

before drug administration on every 15th day during the treatment and at the end of 3rd monthduring follow up (Form III). Required laboratory investigations will be carried out to excludecases as specified in the criteria for exclusion. (Form-IV)


Relief in subjective parameters viz. dryness, pain, redness, foreign body sensation andimprovement in tear film breakup time, Schimers tests will be considered as significant response.





XII. ETHICAL REVIEW

Each Institutional Ethical Committee (IEC) of participating centre’s should giveclearance certificate before the project is initiated. Patient’s information sheet andinformed consent form should be submitted alongwith project proposal for approval byIEC. Both should be maintained in duplicate with one copy given to the patient at thetime of entry to the trial.

XIII. TRAVELLING EXPENSES FOR RESEARCH SUBJECTS

A consolidated amount of Rs.------/ per visit i.e., on the 1st day of recruitment afterscreening, 15th, 30th, 45th, 60th day & end of 3rd month (6 times)





505


CLINICAL EVALUAT ION OF THE EFFECT OF TARPANA AYUSH-DE EYEDROPS, AYUSH-DE CAPSULES IN THE MANAGEMENT OF DRY EYE


CONSENT FORM




Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the “Clinical evaluation of the effect of tarpana and eye drops in the management of dry eyesyndrome (shushkakshipaka / parishushka netra)”





Relationship ___________________________________


506


CLINICAL EVALUAT ION OF THE EFFECT OF TARPANA AYUSH-DE EYEDROPS IN THE MANAGEMENT OF DRY EYE SYNDROME

(SHUSHKAKSHIPAKA / PARISHUSHKA NETRA)



In certain conditions, there is insufficiency of lubrication of eye and the conjunctivabecomes dry. Deficiency in any components of tear film, results in dryness of the eye, due to theappearance of dry spots on the corneal and conjunctival epithelium. Sushruta consideredshushkakshipaka as an individual disease and classified under sarvagata netra rogas. Some clinicalstudies on this condition revealed promising results in managing this condition. The present studyaims at evaluating effect of topical and internal medication in the management of dry eye syndrome.Approximately 50 patients will be included in the trial.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately4months to complete (3 months ofmedication and thereafter 1 month follow up). During this period, you are expected to visit thehospital initially for five days for Tarpana. During the trial you are expected to visit 8 times, at aninterval of every 15 days in first 3 months and at the end of 4th month.

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination; required objective tests will also be done.


At each visit, you will be supplied with sufficient quantities of drugs to last untilyour next visit. If any adverse reactions like skin allergy, nausea, vomiting andpalpitation/tremor etc., noticed during the treatment period, this should be inforrmed tothe Principle Investigator.


507


CLINICAL EVALUAT ION OF THE EFFECT OF TARPANA AYUSH-DE EYEDROPS IN THE MANAGEMENT OF DRY EYE SYNDROME

(SHUSHKAKSHIPAKA / PARISHUSHKA NETRA)


BEFORE TREATMENT


1. Subject Name : ......................................................... Age ................ Sex .........................

2. Centre : ...................................

3. Code No. (of clinical trial) :

4. Patient No.


Third 3 Fourth 4

CRITERIA FOR SELECTION Yes No

1. Dryness of the Eye with or without

2. Sandy and scratchy feeling

3. Pain / pricking sensation

4. Photophobia

5. Mild redness/ Mild blepharitis

6. Less flow of tears even when exposedto irritant odor and fumes

7. Foreign body sensation

8. Mild redness


508

10. Tear film break-up time

11. Rose Bengal staining showing devitalizedepithelium of conjunctiva and mucus plaqueson the cornea. (Value)

12. Schimers tests positive (Value)

13. Chronicity upto 6 months

EXCLUSION CRITERIA Yes No

14. Age below 20 years above 40 years

15. Chronicity above 2 years

16. Corneal ulcer

17. Vitamin-A deficiency

18. Degenerative condition of conjunctiva

19. Extra ocular and intra ocular infections


If Sl. No. 1-13 is ‘Yes’ and Sl. No. 14-19 are ‘No’

Date ______________ Signature of Investigator____________________

509

COUNCIL FOR RESEARCH IN AYURVEDA AND SIDDHA



CASE REPORT FORM -II HISTORY


1. Subject Name : ......................................................... Age ................ Sex .........................

2. Address : ..............................................................................................................................

3. Date of Asmission : ................................................ Date of Discharge ...............................

4. Centre : ...................................


6. Patient No.


Third 3 Fourth 4








1. Environment : __________________

2. Income 10, 000 & >

10, 000 & <

510

Chief complaint with duration (in month)


9. Dryness of the eye

10. Sandy and scratchy feeling

11. Pain / pricking sensation

12. Photophobia

13. Mild redness/ Mild blepharitis

14. Less flow of tears even when exposed to irritant odour and fumes

15. Foreign body sensation

16. Mild redness

17. Others specify: ......................................................................................................................



19. Duration of disease (in months):

PERSONAL HISTORY

20. Diet Veg 1 Non-veg 2 Lacto-ova veg 3

21. Sharirik Prakriti (please see separate attached sheet)



Sannipataja 7

PHYSICAL EXAMINATION: Normal Abnormal


511

SYSTEMIC EXAMINATION:

Normal Abnormal


EXAMINATION OF THE EYE

Vision examination

Normal Abnormal

If abnormal, specify_______________________________________________________

Movement

Normal Abnormal

If abnormal, specify_______________________________________________________

Lacrimal System Normal Abnormal

(ashruyantra)

If ‘abnormal’ specify, ______________________________________________________

Conjunctiva (bulbar)

Congestion (GRADE 0-5) _________________________________

Oedema (GRADE 0-5) _________________________________

Haemorrhage (GRADE 0-5) _________________________________

Redness (GRADE 0-5) _________________________________

Nodule (GRADE 0-5) _________________________________

Conjunctiva (tarsal)

Tarsal scarring (GRADE 0-5) _________________________________

Fllicles (GRADE 0-5) _________________________________

Others (GRADE 0-5) _________________________________

512

Sclera (Sukla mandala)

Change in colour (GRADE 0-5) _________________________________

Pigmentation (GRADE 0-5) _________________________________

Nodule (GRADE 0-5) _________________________________

Congestion (GRADE 0-5) _________________________________

Cornea (Krishna mandala)

Lusture Normal Lustureless

Vascularisation Sensation 1 Present Absent 2

Reduced 3

Epithelial status Tearfilm meniscus Defect / erosion / desquamated

Tear film break-up test _________________________________

Rose Bengal staining _________________________________

Shchimer tests _________________________________


513





(0 day, 15th, 30th, 45th, 60th, days & end of 3rd month)


1. Centre: ______________________________



4. Address : _______________________________________________________________



7. Dryness of the eye (GRADE 0-5) _______________________

8. Sandy and scratchy feeling(GRADE 0-5) _______________________

9. Pain / pricking sensation (GRADE 0-5) _______________________

10. Photophobia (GRADE 0-5) _______________________

11. Redness/ Mild blepharitis (GRADE 0-5) _______________________

12. Less flow of tears even when exposed to _______________________irritant odors and fumes (GRADE 0-5).

13. Foreign body sensation (GRADE 0-5) _______________________

14. Redness (GRADE 0-5) _______________________

15. Others (specify) Present 1 Absent 2

514

Clinical Tests

15. Tear film break-up test: ______________________________

16. Rose Bengal staining: ______________________________

17. Shchimer tests: ______________________________

18. Status of the patient: Continuing 1 Drop out 2

Reason: ____________________________________________


515




CASE REPORT FORM IV – LABORATORY INVESTIGATIONS ANDPHYSIOLOGICAL PARAMETERS

(Sl.No.5 to 17will be done at 0 & 15th day and 18-20 at the end of 1st, 2nd month,3rd and 4d month)

1. Centre: ______________________________



4. Address : _______________________________________________________________




8. TLC (Cells/Cmm.): ___________________

9. DLC: P (%) _______ L (%) _______ E (%) _______ M (%) _______ B (%) _______

9. Hb (g/dl): ___________________

10. Platelet: ___________________

11. ESR (1st hour.) (mm): ___________________

12. Blood Sugar Fasting & PP (mg./dl): ___________________

13. B. Urea (mg./dl): ___________________

14. S. Creatinine (mg./dl): ___________________

15. Liver function tests (SGOT/SGPT): ___________________

16. Lipid profile: ___________________


516

Blank

517

Drug : Study Code:


CLINICAL EVALUATION OF AYUSH –AC EYE DROPSIN SIMPLE ALLERGIC CONJUNCTIVITIS

(KAPHAJA ABHISHYANDA)


518

Blank

519

I. BACKGROUND

Allergic conjunctivitis1 is commonly occurring ocular problem in day-to-day ophthalmicpractice. Apart from phlyctenular conjunctivitis as a manifestation of endogenous allergy and springcatarrh an exogenous allergy, the conjunctiva may react to many other sensitizing factors viz.external, physical or chemical. Allergy as a cause of conjuctival congestion has however beenexaggerated. (Anything which does not fall into the description of a specific condition and anycondition show aetiology is undermined is often attributed to allergy.) This evasive diagnosis isfurther supported by the favorable response of the conjuctival congestion to steroids (Dhanda etal. 996).

Current line of management advocates the use of topical steroids/ decongestant drops/Mast Cell Stabilizers along with anti-histamine agents, is found unsatisfactory and temporary,should be repeated only during exacerbations, besides their adverse effects (Anonymous, 1996).At this juncture it becomes essential to explore safe effective drug which could effectively tacklesuch conditions. Ayurvedic literatures have recorded more than 60 plant drugs useful in thetreatment of various eye disorders. Daruharidra (Berberis aristata DC.), one of such agents haspotent anti-inflammatory and anti-allergic action.

[Netrarujahara (Analgesic ophthalmic action), Netrakanduhara (anti-allergic action),Kaphajabhisyandahara (Effective in allergic ocular conditions) (SrikanthN.2000).] Berberine, analkaloid isolated from B. aristata and its salt berberine hydrochloride produced depressant effecton histamine, 5-HT and Bradykinin. It exhibited anti-inflammatory property on acute, sub-acuteand chronic models of inflammation. Clinical application of berberine in chronic trachoma patientsby intraconjuctival injection proved highly effective. The effect confirmed by scientific studies, thatrevealed “Berberine may prove practical remedy for large scale use in trachoma patients. Berberinein a dose of 0.5 mg per egg protected 50-75% chick embryos from the lethal effect of thetrachoma organisms inoculated into the yolk sac”. The results supported the ancient Ayurvedicclaims on the use of the plant B. aristata in eye diseases and clinical report on the efficiency ofberberine in trachoma. (Bhatnar1970, Halder 1970,Imaz 1977, Verma. RL.1993, Anonymous


CLINICAL EVALUATION OF AYUSH –AC EYE DROPS IN SIMPLEALLERGIC CONJUNCTIVITIS (KAPHAJA ABHISHYANDA)

References

1. Ambika Dutta Sashtri (1989) Sushruta samhita (text with Hindi commentary) Uttara Sthana, VIIthEdition Chaukhamba Sanskrit Series Office, Varanasi.

2. Actions & uses of indigenous ophthalmic drugs, Chaukhamba Sanskrit Pratisthan, New Delhi

520

1996) it may be concluded that the decoction of the Daruharidra may be successfully employedin the management of acute and chronic conjunctivitis of varied aetiology.

A clinical study of 52 cases of Allergic conjunctivitis was conducted to evaluate the effectof a potent Anti- inflammatory, and Anti- Allergic Indigenous Ophthalmic Drug -Daruharidra(Berberis aristata DC.). Topical administration (Aschyotana) with decoction of root bark ofDaruharidra (Berberis aristata DC.) was scheduled for 5 days and Aschyotana procedure wasrepeated for the same period at an interval of 7days.Follow up observation was done for onemonth. This study reveled that the scheduled therapy is highly valuable in the management ofallergic conjunctivitis of varied aetiology. The response obtained may be explained with the anti-allergic, anti-inflammatory, antibacterial, properties attributed to the drug (Bhatnar1970, Halder1970, Imaz 1977, Sabir 1976, Verma. RL. 1993, Anonymous 1996) besides its Netrarujahara(Analgesic Ophthalmic action), Kaphajabhisyandahara (effective in allergic ocular conditions), andNetrya (Conducive to Eye) actions.

II. OBJECTIVE

To evaluate the effect of Ayush –AC eye drops in simple Allergic Conjunctivitis (KaphajaAbhishyanda)

III. CENTRE

Central Research Institute (Ay.), New Delhi


Sample Size _ 90 patients (2 Groups)

Design of the study – Randomized Control Trial


Ayush-AC Eye Drops {containing equal parts of Daruharidra (Berberis aristata) andSirisha (Albizia libeck)} three times a day for 15 days.

Control - Distil water + preservative used in the drug

Duration of the study - 1½ months including 15 days drug therapy witha follow up for one month without drug.

Period of Study - 15 days for each case. Total duration will be oneyear to complete the trial.

Follow – up - One follow-up will be carried out after one week ofthe completion of treatment.


1. Patients presenting with cardinal features of allergic conjunctivitis viz.

• Redness

521

• Itching

• Lacrimation

• Irritation

• Photophobia.

2. Age >10 yrs.

3. Conjunctival smear negative for bacterial/viral (optional)/fungal infection.


1. Age below 10 yrs

2. Conjunctival smear showing evidence of infection.

Clinically diagnosed cases of

3. Infective conjunctivitis

4. Parasitic infestation



During the course of the trial treatment, if any serious condition develops/ symptomsaggravates, which requires urgent treatment, if no response after one week of treatment suchsubjects may be withdrawn from the trial and managed by the Principal Investigator accordingly.


The full details of history and physical examination of the patients will be recorded as perthe proforma (Forms I & II). Clinical assessment will be done before drug administration on 15th

day during drug therapy and 30th day & 45th during follow up (Form III). Required laboratoryinvestigations i.e. Stool examination (3 samples), TC (Cells/Cmm.), DC (P, L, E, M and B),Absolute eosinophil, Hb% (g/dl), ESR (1st hour.) (mm), Blood Sugar – random (mg./dl,Conjunctival swab for light microscopy and C&S evaluation will be carried out to exclude casesas specified in the criteria for exclusion. (Form-III)

IX. CRITERA FOR ASSESSMENT

Disappearance of Redness, Itching, Lacrimation, Irritation and Photophobia will beconsider ed as significant out come of the treatment.


Data on clinical symptoms and objective tests before and after the treatment will betabulated and analyzed using appropriate statistical tools. However, the data of each case will haveto be communicated on completion of trial therapy to the Statistical Officer of CCRAS throughe-mail.

522







A consolidated amount of Rs. ______/- per visit.





523


PROTOCOL FOR CLINICAL EVALUATION OF AYUSH –AC EYE DROPS INSIMPLE ALLERGIC CONJUNCTIVITIS (KAPHAJA ABHISHYANDA)





Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the “Clinical Evaluation of Ayush –AC Eye Drops in simple Allergic Conjunctivitis (KaphajaAbshyanda)”





Relationship ___________________________________


524





Allergic conjunctivitis is commonly occurring ocular problem in day-to-day ophthalmicpractice. Apart from phlyctenular conjunctivitis as a manifestation of endogenous allergy and springcatarrh an exogenous allergy, the conjunctiva may react to many other sensitizing factors viz,external, physical or chemical. Experimental and clinical studies revealed that drugs undertaken inthe study viz. Daruharidra and Sirisha have significant effect of in the management of allergicdisorders including allergic conjunctivitis. The present study aims at evaluating effect of [Ayush-ACcapsules &] Ayush-AC drops in the management of allergic conjunctivitis.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 22 days to complete (15 days ofmedication and thereafter one week of follow up). During this period, you are expected to visitthe hospital three times at the interval of one week.

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination, blood samples will also be taken to make sure that you are eligible for thestudy.




525



SYNDROME (SHUSHKAKSHIPAKA / PARISHUSKHA NETRA)


BEFORE TREATMENT


1. Centre : ...................................


3. Subject Name : ....................................................................................................................

4. Date of Birth : Age (in yrs.) :

5. Address : ..............................................................................................................................


1. Patients presenting with cardinal features of allergic conjunctivitis viz.

• Redness,

• Itching,

• Lacrimation,

• Irritation

• Photophobia.

2. Age >10 yrs

3. Conjunctival smear negative for bacterial/viral (optional)/fungal infection.


4. Age below 10 yrs

526

5. Conjunctival smear showing evidence of infection.

6. Infective conjunctivitis

7. Parasitic infestation




If admitted: Serial No._______________ No of Packet issued_________________

Date ___________________ Signature of Investigator:____________________

527



Case Report form-II history


1. Centre : ...................................


3. Subject Name : ....................................................................................................................

4. Patient No.


6. Address : ..............................................................................................................................








Indicate nature of work ...........................................................................

9. Total family members :


528



11. Redness

12. Itching

13. Photophobia

14. Lacrimation

15. Irritation

16. HISTORY OF PRESENT ILLNESS

I. Onset of disease Acute 1 (1) Insidious 2 (2)

II. Duration of disease (in months)

III. Factors aggravating the disease/chief complaints ______________________________

IV.Factors relieving main complaints __________________________________________

V. History of past illness, having relation with present illness : Yes No

If yes, Specify____________________________________________________________

VI. Contact with pets _____________________________________________________

17. PAST HISTORY Yes (1) No (2)

I. Working in agriculture field

II. Contact with pets

III. Hay fever, asthma, eczema

IV. Use of hair dye

V. Use of systemic antibiotics (Sulphanomides)

18. PERSONAL HISTORY

19. Diet: Veg 1 Non-veg 2 Lacto-ova veg 3

Fish-veg 4

529

20. Sharirik Prakriti: Vata 1 Pitta 2 Kapha 3


Sannipataja 7

21. Manas Prakriti : Sattva 1 Rajas 2 Tamas 3

Sattva-Rajas 4 Rajas-Tamas 5 Sattva-Tamas 6

Sama 7

22. EXAMINATION OF THE EYE (NETRA PARIKSHA)

I. Vision

II. Palpebral fissure (Vartma sukla sandhi) Wide 1 Narrow 2

III. Eyeball (Akshigolaka)

(a) Size Normal 1 (1) Microphthalmos 2 (2) Big 3

IV.Lids (Vartma)

(a) Position Normal 1 Drooping 2

(b) Thickness Present 1 Absent 2

(c) Inflammatory signs Present 1 Absent 2

(d) Lashes

Misdirection Present 1 Absent 2

Scantiness Yes 1 No 2

(e) Lidmargin

Ectropion Yes 1 No 2

Entropian Yes 1 No 2

V. Lacrimal System Normal 1 Drooping 2(ashruyantra)

If ‘abnormal’ specify, ___________________

530

VI. Conjunctiva (bulbar) Yes (1) No (2)

Congestion

Conjunctival/CCC

Oedema

Hemorrhage

Redness

VII. Conjunctiva (tarsal) Yes (1) No (2)

Nodule

Others Yes

VIII. Sclera (Sukla mandala) Yes (1) No (2)

Change in colour

Pigmentation

Nodule Yes

Congestion

IX. Cornea (Krishna mandala) Present (1) Absent (2)

(a) Opacity

(b) Oedema

(c) Vascularisation

(d) Epithelial status

(e) Keratitis


X. Anterior Chamber

If abnormal, specify: .............................................................................................................

531

XI. Iris (Mamsa ashrita patala)


XII. Vitreous


Lens (Medoashrita patala)

(a) Opacity Present Yes (1) No (2)


XIII. Pupil (Dristi mandal)


XIV. Retina (Asthiashrita patala)


XV. IOP (Digital)



532




1. Centre: ______________________________



4. Address : _______________________________________________________________



7 Redness (Grade 0-5) _________________________________________

8 Itching, (Grade 0-5) _________________________________________

9 Photophobia. (Grade 0-5) _________________________________________

10 Lacrimation, (Grade 0-5) _________________________________________

11 Irritation (Grade 0-5) _________________________________________

12 Adverse reaction: _____________________________________________________

If yes, details____________________________________________________________

13 Overall impression of well-being by the Subject:


14 Status of the patient:

Continuing (1)

Drop out (2) Reason: _____________________________

Died (3) Cause: ______________________________

Date: ______________ Signature of Investigator__________________________

533


PROTOCOL FOR CLINICAL EVALUATION OF AYUSH – AC EYE DROPS INSIMPLE ALLERGIC CONJUNCTIVITIS (KAPHAJA ABHISHYANDA)

CASE REPPOT FORM IV – LABORATORY INVESTIGATIONS

(Before treatment)

1. Centre: ______________________________



4. Address : _______________________________________________________________






Ova/Cyst____________ Occult Blood____________\

9. TC (Cells/Cmm.)_____________________

10. DC: P (%)_______ L (%) _______ E (%)________ M (%)________ B (%)_______

11. Absolute Eosinophils

12. Hb (g/dl): _______________

13. ESR (1st hour.) (mm) _______________

14. Blood Sugar – Randomized (mg./dl) _______________

15. Conjunctival swab for light microscopy and C & S evaluation


534

Blank

CONNECTIVE TISSUE DISORDER

SEC

TIO

N - V

III

536

Blank

537

Treatment modality: Study Code:


CLINICAL TRIAL ON EVALUATION OF EFFECT OFJALAUKAVACHARANA IN DEEP VEIN THROMBOSIS


538

Blank

539

I. BACKGROUND

Presence of thrombosis1 within a deep vein and accompanying inflammatory response inthe vessel wall is termed as thrombosis of deep vein. Most important consequences of deep veinthrombosis is pulmonary embolism. More than 90% of pulmonary embolism arise from deep veinthrombosis (William F.; Baker Jr., 1998) Pulmonary embolism has mortality of 18.3% withouttreatment (Kemp PM, Traror D Batty V. et.al., 1996). Once the deep vein thrombosis occurs,the risk of pulmonary embolism is high in first 72 hrs.

Risk factors for Deep Vein Thrombosis: Virchow triad of venous stasis, intimal injury andhypercoagulable state was described in 1856 but still hold some truth.Extensive autopsy and clinicalstudies have shown that 95% pulmonary embolism arise from deep vein thrombosis in the lowerlimbs. Indwelling catheter in upper extremity veins like superior vena cava and right ventricle caninduce thrombosis.

Prevention of pulmonary embolism is the most important aim of treating the patient withdeep vein thrombosis. Prophylaxis is achieved by drug like heparin, LMW heparin or oralanticoagulant and physical method like intermittent leg compression and graduated compressionstocking. In the early phase thrombolytic maybe useful in clot lysis.

Due to high cost of thrombolytics and LMW Heparin and bleeding and thrombo-cytopenic side effect of heparin, the future Ayurvedic procedure Jalaukavacharana (leechapplication) which has low cost and no side effect hold a strong promise for development of abetter procedure. Previous studies showed Jaloukavacharana as a promising treatment for deepvein thrombosis. The same needs to be verified further.

II. OBJECTIVE

To evaluate the effect of Jalaukavacharana (leech application) in deep vein thrombosis.


CLINICAL TRIAL ON EVALUATION OF EFFECT OF JALAUKAVACHARANAIN DEEP VEIN THROMBOSIS

References

1. Harisson’s Principles of internal medicine, 14th Edition, International Editions, 1998, Publishedby McGraw-Hill CompaniesInc.pp1652

540

III. CENTRES



Sample size : 20 in each centre

Procedures of leech application:

1. Pre-operative procedure:

i Preparation of leech: Before using for blood letting, the leeches should bepurified by keeping them in water mixed with turmeric powder for sometime. Then, they should be shifted to the fresh water.

ii Preparation of patient: Thoroughly examined patient should be made totake comfortable and convenient lying down position. The part of thebody where leech is to be applied should be cleanly washed and dried bywiping with cotton cloth or swab. Antiseptic lotion or oil etc. should not beused.

2. Operative procedure:

Then one or two leeches depending on the condition should be applied to theswollen and indurated part of the limb. If the leech does not suck the blood, a drop ofmilk or blood should be; put on the site. Still if leech fails to such the blood, mild prickshould be made on the skin. After the leech starts sucking the blood, it should be coveredwith a wet cloth. If at biting site, pricking pain and itching appears, the leech should beremoved, if it does not leave, its mouth should be sprinkled with the turmeric powder.

3. Post operative procedure:

i Care of patient: After detachment of the leech, bleeding may continue. Atthat time turmeric powder should be applied on the bleeding spot andwashed with cold water and dried by gently pressing with a gauze. Thento enhance the healing process, Jatyadi Taila should be applied andbandaged.

ii Care of leech: In order to make the leech fit for further use, it should bemade to vomit the sucked blood, by keeping it in the water mixed withturmeric powder followed by holding it upside down and applying mildpressure on the body of the leech from tail to mouth. After completevomiting it should be washed out with cold water and kept in the pot.After 7 days, we can make use of the same leech for blood letting.

541

Duration of the Procedure- Application of leech will be done twice a week with aninterval of 3 days. Total duration of the procedure is 1 month.

Design of the study – Open Trial

Total period of study- 12 months


1. Both sexes

2. Between 25 years and 70 years.

3. Unilateral swelling of lower limb

4. Warmth and erythema over swelling

5. Tenderness over swelling

6. Calf pain (Posterior calf tenderness)

7. History of Immobilization for more than 2 weeks

8. Post menopausal hormonal replacement therapy

9. Patient with hemodynamically stable

10. Patient with positive finding of thrombosis on the basis of intravascular Doppler Study


1. Patient with hamodynamically unstable

2. Patient with Bleeding disorder

3. Patient with Respiratory failure

4. Severe CCF with EF < 30%

5. Severe uncontrolled diabetes

6. Acute MI

7. History of recent haemorrhagic stroke



During the course of trial treatment, if any serious condition develops which requiresurgent treatment; such subjects may be withdrawn from the trial and managed by the PrincipalInvestigator accordingly.

542


The full details of history and physical examination of the patients will be recorded as perthe proforma (Forms I & II). Clinical assessment will be done before and after the procedure. Thelaboratory investigations and the physiological parameters will be recorded before and at the endof treatment


Clinical symptoms, physiological parameters and laboratory parameters will be analysedusing appropriate statistical methods.

X. CRITERIA FOR ASSESSMENT OF RESULTS

Relief in clinical signs and symptoms will be considered as significant improvement.


The progress of the trial will be monitored by Monitoring Unit and staff of CCRASHeadquarters, New Delhi).

Data analysis will be undertaken at the CCRAS Headquarters, New Delhi.

XII. ETHICAL REVIEW

Each participating center’s Institutional Ethical Committee (IEC) should give clearancecertificate before the project is initiated. Patient’s information sheet and informed consent formshould be submitted alongwith project proposal for approval by IEC. Both should be maintainedin duplicate with one copy given to the patient at the time of entry to the trial.

543






Name: ____________________________

CONSENT BY SUBJECT

I have been informed to my satisfaction, by the attending physician, the purpose of theclinical trial and the nature of treatment and follow-up, including the laboratory investigations to beperformed to monitor and safeguard my body functions.

I am also aware of my right to opt out of the trial at any time during the course of the trialwithout having to give the reasons for doing so. I, exercising my free power of choice, herebygive my consent to be included as a subject in the “Clinical trial on evaluation of effect ofJalaukavacharana in deep vein thrombosis.”





Relationship ___________________________________


544





In spite of advances in the medical as well as surgical management of deep veinthrombosis, limited success and their complications pose major concern for scientific community.Jaloukavacharana or application of leech on affected part is proved to be beneficial in deep veinthrombosis. It is the mildest, safest and painless way of extracting impure blood from the vein.After certain preoperative measures the leech is allowed to suck the blood. After the leech leavesthe part, bandaging will be done. It takes about 15 minute to complete the procedure at eachsitting.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 1 month to complete the treatment andanother 6 months for follow-up study). During this period, you are expected to visit the hospitaltwice a week. The interval between the 1st and 2nd visit will be 3 days.


If you are found eligible, you would be put on trial treatment for 1 month. At each visit,you will be treated with the application of leeches.


545




BEFORE TREATMENT


1. Centre : ...................................


3. Subject Name : ....................................................................................................................



6. Address : ..............................................................................................................................


1. Both sexes

2. Between 25 years and 70 years.


4. Warmth and erythema over swelling




8. Post menopausal hormonal replacement therapy

9. Patient hemodynamically stable

10. Patient with positive finding of thrombosis on the basis of intravascular Doppler study

546


11. Patient hamodynamically unstable

12. Patient with Bleeding disorder

13. Patient with Respiratory failure

14. Severe CCF with EF < 30%

15. Severe uncontrolled diabetes

16. Acute MI

17. History of recent haemorrhagic stroke

18. Person undergoing treatment for any other serious illness.



If admitted, Subject’s Serial No. ____________

Date: ____________ Signature of the Investigator ______________________

547





1. Centre : ...................................


3. Subject Name : ....................................................................................................................



6. Address : ..............................................................................................................................






Standing for long time 3

Laborious 4

Sedentary 5





10. Warmth and erythematic over swelling

548


12. Cord like palpation over swelling

13. Cyanotic colour change over swelling

14. Paleness over swelling


History of Past illness Yes (1) No (0)


17. Orthopedic procedure on hip, knee

18. History of trauma (pelvis, femur, tibia)

19. History of intake of oral contraceptive

20. Post menopausal hormone replacement therapy

21. Non-hemorrhagic stroke with immobilization

22. Hypertension

23. Diabetes

24. Tuberculosis

25. Malignancy

26. Major hospitalization/surgery during past three years

If yes, specify ___________________________________________________________

27. Other complaints if any (Specify) _____________________________________________

Personal History

28. Diet Veg 1 Non –veg 2

29. Sleep Normal 1 Abnormal 2

30. Presence of anxiety No 2 Yes 2

549

31. Constipation No 2 Yes 2

Addiction


If yes specify: (a) Quantity (packs) ________________



If yes specify: (a) Quantity (packs) ________________



If yes specify: (a) Quantity (in ml.): ________________


35. Any other (specify): ________________________________________

36. Prakriti Vata 1 Pitta 2 Kapha 3


Sannipataja 7


37. Height (cm) ____________

38. Weight (kg) ____________

39. Pulse (per min) ____________

40. Blood Pressure Systolic(mm Hg) ___________

41. Blood Pressure Diastolic (mm Hg) ___________

42. Body temperature( o F) ___________

43. Respiration rate( per min) ___________

550


44. Anemia

45. Pallor

46. Clubbing

47. Edema

48. Deformities

If present, specify ________________

49. Lymphadenopathy

If present, specify: General 1 Local 2

(Area)__________________________________________________________________

Local Examination Absent (0) Present (1)

50. Pain in calf after dorsiflexion of foot

51. (Horranis sign)


52. CVS


53. CNS




55. Per abdomen


551





58. Locomotor system


Date:_________________ Signature of Investigator____________________

552



FORM III – CLINICAL ASSESSMENT

(0,………………..)


1. Centre: ______________________________



4. Address : _______________________________________________________________







10. Warmth and erythematic over swelling


12. Cord like palpation over swelling

13. Any cyanotic color change over swelling

14. Paleness over swelling


16. Any other non-specific symptoms

If yes, Present specify_________________________

553

17. Overall clinical assessment by the Investigator:



Continuing 1

Drop out 2 Reason: _____________________________

Died 3 Cause: _______________________________


554



FORM IV– LABORATORY INVESTIGATIONS AND PHYSIOLOGICALPARAMETERS

(Before and after the treatment)


1. Centre: ______________________________



4. Address : _______________________________________________________________





9. Hb%

10. Urine

Routine: ____________ Microscopic: ____________

9. Stool for occult blood: ____________

10. TLC: ____________

10. DLC: P (%) _______ L (%) _______ E (%) _______ M(%) _____ B (%)_______

11. ESR: ____________

12. BT: ____________

13. CT: ____________

555

14. PT: ____________

15. APTT: ____________

16. Platelet count : ____________

17. Lipid profile: ____________

18. Serum total cholesterol: ____________

19. Serum triglyceride: ____________

20. High density lipoprotein: ____________

21. Very low density lipoprotein: ____________

22. X-Ray Chest: ____________

23. ECG 12 leads: ____________

24. LFT : S.Bilirubin, SGOT, SGPT, S.Alkaline phosphatase, S.Albumin, S.Gobulin, A/G ratio

25. KFT: BUN, S.creatinine, Blood sugar, Serum Antithrombin,

26. Blood sugar

Fasting: ____________ Post Prandial: ____________

27. Serum Antithrombin

28. S.Sodium,

29. S.Potassium

30. USG:Duplex venous ultra-sonograph (B-mode) –colour droppler

31. Real time B-mode Compression Ultrasound

Date:________________ Signature of Investigator_______________________

556

Blank

GERIATRIC DISORDERS

SEC

TIO

N - IX

558

Blank

559

Treatment modality: Study Code:


MULTICENTRIC OPEN CLINICAL TRIAL OFRASAYANA DRUGS IN HEALTHY ELDERLY PERSONS


560

Blank

561

I. BACKGROUND

The World Health Organization (WHO) has defined Health as a state of physical, mentaland social wellbeing and not only the absence of disease or infirmity. Over the years, this definitionhas changed and now Health is seen as a more holistic state including spiritual component in it.This present definition of Health by WHO closely resembles the definition laid down in Ayurvedictexts, more than 3000 years ago. The emphasis on maintaining good health or Swasthya is crucialto Ayurveda. Ayurveda has presented a total holistic approach for upliftment of body and mind aswell as spirit. Whatever is possible through the control of mind and prana, can be acquiredthrough Rasayana. Rasayana therapy1 (Rejuvenating group of medicines) aims specially at thepromotion of strength and vitality by replenishing rasa and other Dhatus. The other benefitssecured by Rasayana therapy are promotion of memory and intelligence, immunity against diseaseand decay, preservation of youthfulness, lustre, complexion and voice.

Rasayana is of three types according to their effect – 1. Ajasrika (nutritional) 2. Kamya(desirable) and 3. Naimittika (conditional) and of two types according to the methods ofapplication - 1. Kutipravesika (confined treatment under specified atmosphere) and 2. Vatatapika(usual out patient treatment).

There are numerous rasayana drugs among which important ones are Amalaki, Bhallataka,Nagabala, Pippali, Aswagandha, Shilajit and Svarnabhasma. Brahmi, Shankhapushpi, Guduchi andYastimadhu are particularly intellect promoting (Medhya) rasayana drugs though they also promotephysical strength.

A series of clinical and experimental studies have already been conducted to assess theRasayana effect of many single and compound preparations. The studies on Chyavanprasa andAmalaki Rasayana showed significant health promotive effect in elderly volunteers. The PippaliKsirapaka provided significant Naimittika rasayana effect in the patients of Tuberculosis, Asthmaand Arthritis reflected through increase in body weight, nitrogen retention, serum protein andhaemoglobin.


PROTOCOL FOR MULTICENTRIC OPEN CLINICAL TRIAL OF RASAYANADRUGS IN HEALTHY ELDERLY PERSONS

References

1. Kasinatha Sastri (1970), Caraka samhita Part-II, First edition, The Chowkhamba Sanskrit SeriesOffice, Gopal Mandir Lane, P.O. Chowkhamba, Post Box – 8, Varanasi – 1, India.

562

The study on the Medhya Rasayana effect of Shankapushpi, Brahmi and Mandukaparnishowed significant improvement in neurological and psychological parameters. The effect of Brahmion acetylcholine, acetylase and cholinesterase has been better than Mandukaparni. Similar studieswere also conducted on Satavari and Vacha with encouraging results.

Aswagandha when administered to 106 apparently normal healthy male volunteers in theage group of 50-59 years was found to have anti-aging effect. Another study established thehaematinic effect of Aswagandha when administered with milk for 60 days to 60 children. Theeffect of another Ayurvedic compound consishting of

Shatavari, Punarnava, Bala, Guduchi, Amalaki and Yasti in 50 apparently healthy malevolunteers in the age group of 45-50 years indicated that the compound has capability of restoringthe age - related functional impairments. A series of clinical studies conducted in different institutesrevealed that Amalaki (Emblica officinalis) as an effective remedy for different gastrointestinalproblems besides its Rasayana effect.

II. OBJECTIVES

• To observe the effects of Rasayana regimen (Triphala churna 5gm OD at night andAshwagandha churna 5gm OD at morning daily with water for 4 months) on physicalperformance, quality of life and metabolic milieu.

• To observe the clinical safety of Rasayana regimen on clinical & laboratory parameters.

• Effect of Rasayana regimen in apparently healthy elderly on

a. Physical strength

b. Balance

c. Sleep

d. Urge incontinence

e. Constipation

f. Stress level

g. Quality of life

h. Vague ache and pains/ stiffness

i. Appetite

2. Adverse effect of regimen

a. In apparently healthy elderly person with no systemic disease

b. In person with systemic disease like hypertension and drug interactions

563

III. CENTRES



Sample Size: 50 subjects per center (Total 250 participants)


Drug: Triphala churna 5gm OD at night and Ashwagandha churna 5gm OD at morningdaily with water for 4 months.

Design of the study: Multicentric open clinical trial

Duration of the study: 4 months.



2. Apparently healthy

3. Co-operative and fully conscious



2. Severe bronchial Asthma /COPD

3. Cancer

4. Dementia < 24 score

5. Any symptomatic cardiac disease

6. Chronic debilitating conditions like hepatic/ renal insufficiency (Confirmed through history/clinical examination)

7. Any acute illness/ serious illness

8. Fever/ delirium


1. Any serious intercurrent illness

2. Any serious adverse effect or drug interaction

564


A. The full details of history and physical examination of the patients will be recorded as perthe Case Record Forms (I & II). Clinical assessment including recording of common signs/symptoms of suspected ADRs will be done before drug administration, at the end of 1st,2nd, 3rd & 4th month of treatment (Form III). Laboratory investigations will be carried outbefore drug administration, at the end of 2nd and 4th month of treatment (Form IV).

IX. FOLLOW - UP

Monthly follow-up will be carried out at the end of each month during the four monthstreatment period.


Clinical symptoms, physiological parameters and laboratory parameters will be analyzedusing SPSS 15.0 version with appropriate statistical methods.


The progress of the trial will be monitored by field visits by Monitoring Unit - CCRASHQ, New Delhi. Data analysis will be carried out at the Monitoring Unit.

XII. ETHICAL CLEARANCE

Each participating centre’s Institutional Ethics Committee (IEC) should give clearancecertificate before the project is initiated.

a. List of Clinical Symptoms to be taken into account for assessment using VAS (VisualAnalogue Scale):-

1. Dizziness

2. Constipation

3. Urge incontinence

4. Aching muscles

5. Joint pain

6. Joint stiffness

7. Sleep abnormality

8. Loss of appetite

9. Vague pain

10. Fatigue

565

11. Generalized weakness

b. Clinical parameters to record

1. Height

2. Weight

3. Pulse rate

4. Blood pressure

Supine (diastolic/systolic__________)

Standing (diastolic/systolic__________)

Orthostatic hypotension – Yes/ No

5. Upper mid arm circumference

6. Skin fold thickness

7. BMI (body weight in Kgs./Height in meters2)

8. Waist circumference

9. Waist: hip ratio

10. Grip strength both hands

11. Get up and go test

12. Walking distance in 1 min.

13. General physical examination

c. Scores

1. Geriatric depression score

2. WHO-QOL score/ CDC score for health quality

3. HMSE (Hindi version of mental system evaluation)

4. Hamilton anxiety scale

d. Laboratory investigations

1. Complete haemogram (Complete blood picture)

2. GBP for anemia

3. Complete urine examination

566

4. Serum Iron

5. TIBC

6. Plasma glucose

a. Fasting

b. Post prandial

7. Lipid profile

a. HDL

b. LDL


a. Serum proteins

i. Albumin

ii. Globulin

b. Serum bilirubin

i. Total

ii. Direct

c. SGPT

d. SGOT

e. Serum Alkaline Phosphatase

9. Serum triglycerides


11. Serum electrolytes


a. Blood urea

b. Serum creatinine

13. Serum uric acid

14. Serum Thyroid Stimulating Hormone (TSH)

15. Serum calcium

567

16. Serum phosphates

e. Special tests

1. ECG

2. Pulmonary Function Test (PFT)

f. Marker of inflammation

1. C Reactive Proteins (CRP)

2. TNF ?

3. IL-6

g. Serum melatonin

h. Free radical system

a. Malonyl aldehyde

b. Catalase

c. Super oxide dismutase

d. Glutathione

e. Peroxidase

i. Prostate specific antigen

j. Test for insulin resistance

568


PROTOCOL FOR MULTICENTRIC OPEN CLINICAL TRIAL OF RASAYANADRUGS IN HEALTHY ELDERLY PERSONS





Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as aparticipant in the clinical trial of Triphala churna 5gm OD at night and Ashwagandha churna 5gmOD at morning daily with water for 4 months on the general health of the aged persons.





Relationship ___________________________________


569


MULTICENTRIC OPEN CLINICAL TRIAL OF RASAYANA DRUGS INHEALTHY ELDERLY PERSONS



Ayurveda has laid emphasis on maintenance of positive health and prevention of diseases,besides management/ treatment of diseases. Rasayana Therapy of Ayurveda promotes health ofindividuals especially elderly persons. The present study is aimed to evaluate selected AyurvedicRasayana drugs for their efficacy in the promotion of health of elderly people.

You are invited to participate in this study where you will be provided with the trail drugsand require to take Triphala churna 5gm OD at night and Ashwagandha churna 5gm OD atmorning daily with water for 4 months. Previous observations in clinical and experimental studieshave shown promising effect of these drugs in the promotion of health. About 250 healthy elderlypersons from this and other hospitals around the country will be taking part in this study.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 16 weeks to complete. During thisperiod, you are expected to visit the hospital five times. The interval between the first, second,third, fourth and fifth visits will be four weeks (one month).

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination, ECG and an X-ray, Blood and urine samples, etc. will also be taken. Thisis to make sure that you are eligible for the study.

If you are found eligible, you would be put on trial treatment for 16 weeks. At each visit,you will be supplied with sufficient quantities of drugs to last until your next visit.


570




1. Centre : ...................................


3. Subject Name : ....................................................................................................................



6. Address : ..............................................................................................................................




3. Cooperative and fully conscious



5. Severe Bronchial Asthma/ COPD

6. Cancer

7. Any symptomatic cardiac disease

8. Chronic debilitating conditions like hepatic/ renal insufficiency (Confirmed through history/ clinicalexamination/ laboratory findings*)

9. Dementia (Score <24 )

10. Any acute illness/ serious illness

571

11. Fever/ delirium



If admitted, Subject Serial No.: ______________

Date: ____________ Signature of the Doctor __________________

* Normal range of values for Sl. No. 8

A. Liver function tests

1. S. Bilirubin

• Total: 0.3 – 1.0 mg/dl

• Direct: 0.1 – 0.3 mg/dl

2. SGPT: 0 – 35 IU/L

3. SGOT: 0 – 35 IU/L

4. S. Alkaline phosphatase: 30 – 120 IU/L

5. S. Proteins (Total): 5.5 – 8.0 g/dl

• Albumin: 3.5 - 5.5 g/dl

• Globulin: 2.0 - 3.5 g/dl

B. Renal function tests

6. Blood urea: 15 – 40 mg/dl

7. S. Creatinine: < 1.5 mg/dl

572





2. Centre :__________________

3. Sr. No. of the Subject : ___________________________________________________

4. Subject Name : __________________________________________________________

5. Gender Male (1) Female (2)

D D M M Y Y

6. Date of Birth : Age (in years.)

7. Address : ..............................................................................................................................









10. Type of living arrangement

Living alone 1

Living with his/her spouse 2

573

Living with his/her family 3

Living in an old age home 4

Others (specify) 5

11. Income (per capita per month) of the participant and Head of the familyin Rs __________________________________________________________________

A. Chief complaint with duration in days

Absent (0) Present (1) Durationin days

12. Dizziness

13. Constipation


15. Aching muscle

16. Joint pain

17. Stiffness

18. Sleep abnormality

19. Loss of appetite

20. Vague pain

21. Fatigue

22. Generalized weakness

B. Recurrent frequent attacks of No (0) Yes (1)

23. Fever

If yes, indicate frequency of attacks in last six months: ____________________________

24. Rhinitis/ upper respiratory tract infection

574


25. Urinary tract infections


26. Other complaints (Specify) _________________________________________________

C. History of Past illness: No (0) Yes (1)

27. Tuberculosis

28. Major hospitalization/ surgery during past three years

If yes, specify ___________________________________________________________

D. Personal History

29. Diet: Veg (1) Non-veg (2)

Addictions Yes (1) No (0)

30. Alcohol

31. Tea/ Coffee more than 4 times a day

32. Tobacco

If Yes, Chewing (1) Smoking (2) Both (3)

33. Prakriti Vata Pitta Kapha

Vata-Kaphaj Vata-Pittaja Pittaja-Kaphaja

Sannipataj

34. Deformities Absent 0 Present 1

If present, specify _________________________________________________________

35. Lymphadenopathy Absent 0 Present 1

If present, specify, General 1 Local 2

Area __________________________________________________________________

575

E. General systemic examination Normal (0) Abnormal (1)


If abnormal, details _____________________________________________________





39. Vision


40. Hearing




42. Central nervous system


43. Cardiovascular system


F. Presence of any of the following symptoms


44. Burning sensation in abdomen

45. Nausea

46. Diarrhoea

47. Skin rashes

Date: ____________ Signature of Investigator _______________________

576



CASE REPORT FORM III A – CLINICAL ASSESSMENT

(ON 0 DAY)

1. Centre: ______________________________


3. Sr. No. of the Subject: ____________________________________________________

4. Name of the Subject: _____________________________________________________


A. Clinical Symptoms Visual Analogue Scale


6. Dizziness

7. Constipation


9. Aching muscles (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

10. Joint pain (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

11. Joint stiffness (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

12. Sleep abnormality (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

13. Loss of appetite (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

14. Vague pain (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

15. Fatigue (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

16. Generalized weakness (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

577

Normal (0) Impaired (1)

17. Vision

18. Hearing

19. Any other non-specific symptoms Absent (0) Present (1)

If present, specify_________________________

B. Physical Examination

20. Height (cm) _____________

21. Weight (kg) _____________

22. Pulse rate (per min) _____________

23. Body temperature (oF) _____________

24. Blood Pressure – Supine Systolic (mm Hg) _____________

25. Blood Pressure – Supine Diastolic (mm Hg) _____________

26. Blood Pressure – Standing Systolic (mm Hg) _____________

27. Blood Pressure – Standing Diastolic (mm Hg) _____________

28. Orthostatic hypertension: Yes (1) No (2)

29. Upper mid arm circumference (cm.) _____________

30. Skin folds thickness (mm) _____________

31. Grip strength (Right hand) (Kg) _____________

32. Grip strength (Left hand) (Kg) _____________

33. BMI (basal metabolic index – wt./ ht.2) _____________

34. Waist circumference (cm.) _____________

35. Waist: hip ratio _____________


578

37. Get up and go test _____________

38. Walking distance in 1 min. _____________

C. Score system

39. Geriatric depression score: _____________

40. WHO-QOL Score/ CDC score for health quality: _____________

41. HMSE (Hindi version of mental system evaluation): _____________

42. Hamilton anxiety scale: _____________

D. No. of sachets issued:

a. Aswagandha Churna sachets _____________

b. Triphala Churna sachets _____________

Date: ______________ Signature of Investigator: ______________________

579



CASE REPORT FORM III B – CLINICAL ASSESSMENT

(ON 30TH DAY, 60th DAY, 90th DAY & 120th DAY)

(USE SEPARATE FORM ON EACH VISIT)

1. Centre: ______________________________





A. Clinical Symptoms Visual Analogue Scale


6. Dizziness

7. Constipation


9. Aching muscles (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

10. Joint pain (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

11. Joint stiffness (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

12. Sleep abnormality (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

13. Loss of appetite (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

14. Vague pain (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

15. Fatigue (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

16. Generalized weakness (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Severe)

580

Normal (0) Impaired (1)

17. Vision

18. Hearing

19. Any other non-specific symptoms Absent (0) Present (1)

If present, specify_________________________

B. Physical Examination

20. Height (cm) _____________

21. Weight (kg) _____________

22. Pulse rate (per min) _____________

23. Body temperature (oF) _____________

24. Blood Pressure – Supine Systolic (mm Hg) _____________

25. Blood Pressure – Supine Diastolic (mm Hg) _____________

26. Blood Pressure – Standing Systolic (mm Hg) _____________

27. Blood Pressure – Standing Diastolic (mm Hg) _____________

28. Orthostatic hypertension: Yes (1) No (2)

29. Upper mid arm circumference (cm.) _____________

30. Skin folds thickness () _____________

31. Grip strength (Right hand) (Kg) _____________

32. Grip strength (Left hand) (Kg) _____________

33. BMI (basal metabolic index – wt./ ht.2) _____________

34. Waist circumference (cm.) _____________

35. Waist: hip ratio _____________


581

37. Get up and go test _____________

38. Walking distance in 1 min. _____________

C. Score system

39. Geriatric depression score: _____________

40. WHO-QOL Score/ CDC score for health quality: _____________

41. HMSE (Hindi version of mental system evaluation): _____________

42. Hamilton anxiety scale: _____________

D. Presence of any adverse reactions Absent (0) Present (1) Duration(in days)


45. Nausea

47. Diarrhoea

49. Skin rashes

47. Overall clinical assessment by the Doctor:

Improved 1 (1) No change 2 (2) Deteriorated 3 (3)




Continuing 1

Completed 2

Drop out 3 Reason: ______________________________________

Died 4 Cause of death: _______________________________

582

D. No. of sachets issued (if continuing):

a. Aswagandha Churna sachets __________________

b. Triphala Churna sachets __________________

Date: ______________ Signature of Doctor _____________________

583




(ON 0 DAY, 60th DAY & 120th DAY)

(USE SEPARATE FORM ON EACH VISIT)

1. Centre: ______________________________





A. Complete urine examination

6. Routine _______________________________

7. Microscopic ___________________________

B. Complete blood picture and haemogram

8. Total count (Cells/Cu.mm) ______________________

9. Differential count: P ____ (%) L ____ (%) E ____ (%) M ____ (%) B ____ (%)

10. ESR (mm/ 1st hour) _______________

11. M.C.H.C. (g/dl) _______________

12. M.C.V. (fl) _______________

13. PCV (%) _______________

14. Hb (gm/dl) _______________

15. Serum iron (μg/dl) _______________

16. Total Iron Binding Capacity - TIBC (μg/dl) _______________

584

C. Plasma glucose (mg/dl)

17. Fasting _______________

18. Post prandial _______________

D. Lipid profile (mg/dl)

19. HDL _______________

20. LDL _______________

E. Liver function tests

21. Serum proteins (gm/dl) Albumin ________ Globulin_________

Serum bilirubin (mg/dl). Total ________ Direct____________

22. SGOT (IU/L) ______

23. SGPT (IU/L) ______

24. Serum alkaline phosphatase (U/L)

25. Serum triglycerides (mg/dl) _______________

26. Serum cholesterol (mg/dl) _______________

F. Serum electrolytes (mmol/L)

27. Sodium____________

28. Potassium _________

29. Chlorides __________

G. Renal function tests (mg/dl)

30. Blood urea _______

31. Serum creatinine __________

32. Serum uric acid (mg/dl) _________

33. Serum thyroid stimulating hormone (μU/ml) ____________

585

34. Serum calcium (mg/dl) ____________________

35. Serum phosphates (phosphorous) _________________

H. Special tests

36. ECG findings _______________________________

37. Pulmonary function test findings _____________________

I. Marker of inflammation

38. HsCRP (mg/L)_______________________________

39. TNF á (pg/ml) _______________________________

40. IL-6 (pg/ml) _________________________________

41. Serum melatonin (pg/ml) ________

J. Free radical system

42. Melonyl aldehyde

43. Catalase

44. Super oxide dismutase

45. Glutathione

46. Peroxidase

47. Prostate specific antigen ____________

48. Test for insulin resistance ___________

Date: _________________ Signature of the Investigator: ______________________

586




(To be translated in to local language)

Sl. No. of Subject _____________________________________________________________

Name of Subject ______________________________________________________________


(To be issued on 1st visit (0 day), 2nd visit (30th day), 3rd visit (60th day) and 4th visit (90th

day) and taken back on 2nd visit (30th day), 3rd visit (60th day), 4th visit (90th day) and 5th visit(120th day))

Please come for next visit on ______________________________ (Date and time is to befilled by the Investigator)


• Please take 5 gm of Ashwagandha churna (1 sachet) daily at 9 AM with water (approx.150 ml.).

• Please take 5 gm of Triphala churna (1 sachet) daily at 9 PM with water (approx. 150ml.).

• Please return the empty sachets after taking medicine along with the compliance reportform duly filled.



(5 gm of Ashwagandha churna) (5 gm of Triphala churna)


1.

587

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

588

28.

29.

30.

Name of the participant _______________________________________________________

Date: _______________________________________________________________________

Signature or Thumb impression of the participant __________________________________

Signature of the Investigator with date ___________________________________________

590

Blank

591

Drug: Study Code:


DOUBLE BLIND CLINICAL TRIAL OF SIDDHA KAYAKALPA DRUGS IN HEALTHY ELDERLY PERSONS


592

Blank

593

I. BACKGROUND

In Siddha system health is defined as a state of physical, mental, social and spiritual wellbeing, devoid of any degenerative disorders. Kayakalpa drugs ensure preventive aspects and alsothe longevity. In Siddha system, elevation of man to attain the highest eternal bliss forever isregarded as the highest form. Siddha’s Kaya Kalpa paved way for such highest form.

Kaya kalpa is divided into two main categories. One is Kalpa yogam and other is Kalpaavizhtham. Eight types of yogic stages are described which helps in the elevation of man to asupernatural being under kalpa yogam1.

Drugs which are capable of preventing as well as curing chronic and degenerative diseases,and also used as rejuvenators in prolongation of life are called Kalpa avizhtham. Siddha system hasa unique way in the preparation of Kalpa drugs with particular specified herbs, minerals andmetals. It is divided into two categories. One is general and the other is special. The general kalpadrugs are used in normal individuals aiming at promotion of strength, vitality and vigor, improvingmemory and intelligence, immunity against disease and decay, preservation of youthfulness, lusture,complexion and voice. The special kalpa drugs, which are used against chronic and degenerativedisorders specifically to eradicate various disease conditions and bring back the vigor and vitalityin the individuals.

II. OBJECTIVE

To evaluate the efficacy of herbomineral kayakalpa drugs in the promotion of positivehealth in healthy volunteers.

III. CENTRES



DOUBLE BLIND CLINICAL TRIAL OF SIDDHA KAYA KALPA DRUGS INHEALTHY ELDERLY PERSONS

References

1.

594




Drug : Nelli karpam (Nelli vattral powder + abiraga chendooram.

Dosage : Nelli vattral Powder 1 gm. Abiraga Chendooram 200 mg.withhoney twice a day.

Duration : 40 days.

Design of : Randomized double blind Placebo controlled study.the study

Duration of : 40 days drug therapy with a follow up for 6 months without drugthe study

Period of : 220 days for each case. Total duration will be three years toStudy complete the trial at each Centre

Follow – Up : Two follow-up will be carried out after three months and after sixmonths of the completion of treatment


1. Age between 60 and 69 years.


3. Ambulatory and Co-operative.


1. Diabetes

2. Hypertension

3. Bronchial Asthma

4. Cancer

5. Manifest Cardiac ailment

6. AIDS

7. Jaundice

8. Kidney related diseases

9. Dementia Grade II & above

595



During the course of the trial treatment, if any serious condition develops which requiresurgent treatment such subjects may be withdrawn from the trial and managed by the PrincipalInvestigator accordingly.


The full details of history and physical examination of the patients will be recorded as perthe proforma (Forms I & IA). Clinical assessment will be done before preparatory regimen, at theend of five weeks, 3rd month and 6th month during treatment and at the end of 3rd and 6thmonth follow up (Form II). The laboratory investigations and the physiological parameters will berecorded before drug administration, at the end of one month, at the end of treatment and at theend of follow-up. [Form III]


Clinical symptoms, physiological parameters and laboratory parameters will be analyzedusing appropriate statistical methods.

X. CLINICAL ASSESSMENT

List of Clinical Symptoms to be taken into account for assessment using VAS (VisualAnalogue Scale): -

1. Dizzy spells/Giddiness

2. Breathlessness on exertion

3. Tremors

4. Constipation

5. Urgency to micturate

6. Aching muscles or joints

7. Pain/Stiffness in joints

8. Numbness

9. Abnormality in sleep


596


The progress of the trial will be monitored by CCRAS Headquarters, New Delhi. Dataanalysis will be undertaken at Central Research Institute for Siddha, Chennai.

XII. ETHICAL REVIEW

Institutional Ethical Committee (IEC) should give clearance certificate before the project isinitiated. Patient’s information sheet and informed consent form should be submitted alongwithproject proposal for approval by IEC. Both should be maintained in duplicate with one copygiven to the patient at the time of entry to the trial

XIII. TRAVEL LING EXPENSES FOR RESEARCH SUBJECTS

A consolidated amount of Rs…../- per visit will be paid to subject.





597


DOUBLE BLIND CLINICAL TRIALOF SIDDHA KAYA KALPA DRUGS INHEALTHY ELDERLY PERSONS





Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial of Nellikarpam – Nelli vattral powder 1 gm and Abbirga chendooram 200 mg.twice a day with honey for 40 days on the general health of the Aged persons.





Relationship ___________________________________


598





Siddha has laid emphasis on maintenance of positive health and prevention of diseases,besides management/treatment of diseases. Kaya kalpa Therapy of Siddha promotes health ofindividual especially elderly persons. The present study is aimed to evaluate selected Siddha KayaKalpa drugs for their efficacy in the promotion of health of elderly people. You are invited toparticipate in this study where you will be provided a combination of Nelli vattral chooranam 1gmand Abiraga chendooram 200 mg twice a day with honey for 40 days.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 32 weeks to complete (40 days fortreatment and another 24 weeks for follow-up study). During this period, you are expected to visitthe hospital 10 times. The interval between the 1st and second visit will be one week and secondand third visit will be around 10 days. Your next visit will be after one month. There will be fivemore visits after every one-month of last visit.


If you were found eligible, you would be put on trial treatment for 6 weeks. Thedaily dosage will be 1200mg twice. At each visit, you will be supplied with sufficientquantities of drugs to last until your next visit.


599




BEFORE TREATMENT


1. Centre : ...................................


3. Subject Name : ....................................................................................................................



6. Address : ..............................................................................................................................


7. Age between 60 and 79 years of either Sex


9. Ambulatory and Cooperative

10. Diabetes

11. Hypertension

12. Bronchial Asthma

13. Cancer

14. Manifest Cardiac ailment


15. AIDS

600

16. Jaundice

17. Kidney related diseases

18. Dementia (Score >25 on Mini Mental Examination Scale & > one episode of depression or delirium)

19. Under treatment for any other serious illness



If admitted, Sr. No. of the Subject: ______________________________________________

No. of packets issued: ________________________________________________________


601


DOUBLE BLIND CLINICAL TRIAL OF SIDDHA KAYA KALPA DRUGSINHEALTHY ELDERLY PERSONS



1. Centre : ...................................


3. Sr. No. of the Subject : .......................................................................................................

4. Subject Name : ....................................................................................................................



7. Address : ..............................................................................................................................









10. Income (per capita per month in Rs.) : ................................................................................of the participant and Head of the family


Living alone 1

602

Living with his/her spouse 2

Living with his/her family 3

Living in an old age home 4

Others (specify) 5

12. Income (per capita per month) of the participant and Head of the familyin Rs __________________________________________________________________

Chief complaint with duration (if any) Absent (0) Present (1) Duration


13. Constipation

14. Vague Pain

15. Fatigue

16. Dizziness

17. Weakness

18. Forgetfulness

Recurrent frequent attacks of: Yes (1) No (0)

19. Fever

If yes, indicate frequency of attack in months____________________________________

20. Rhinitis/upper respiratory tract infection


21. Urinary tract infection


22. Other complaints

If yes, specify: ___________________________________________________________

603

History of Past illness No (0) Yes (1)

23. Tuberculosis

24. Rheumatic fever

25. Major hospitalization/surgery during past three years

If yes, specify ___________________________________________________________

Personal History


27. Sleep Normal (1) Duration in hours______________________

Abnormal (2) Duration in hours______________________

If Abnormal specify Yes (1) No (0)

(a) Initiation:

(b) Maintenance:

(c) Freshness in the morning:

Yes (1) No (0)

28. Presence of anxiety

29. Constipation

Addiction Yes (1) No (0)

30. Smoking



31. Tobacco



604

32. Alcohol



33. Any other (specify)________________



Sannipataj


35. Height (cm) ______________

36. Weight (kg) ______________

37. Pulse (per min) ______________

38. Blood Pressure Systolic (mm Hg) ______________

39. Blood Pressure Diastolic (mm Hg) ______________

40. Body temperature (o F) ______________

41. Respiration rate ( per min) ______________


42. Anemia

43. Deformities

If present, specify _________________________________________________________

44. Lymphadenopathy

If present, specify: General (1) Local (2)

Area: __________________________________________________________________

605





If abnormal, details ____________________________________________



48. Vision


49. Hearing









606



CASE REPORT FORM III – CLINICAL ASSESSMENT AND PHYSIOLOGICALPARAMETERS

(0, 5 weeks, 3, 6, 9,12th months)

1. Centre : ...................................



4. Subject Name : ....................................................................................................................





Clinical Symptoms Visual Analogue Scale

9. Dizzy spells/Giddiness 0____________________________________10

10. Breathlessness on exertion 0____________________________________10

11. Constipation 0____________________________________10

12. Urgency to micturate 0____________________________________10

13. Aching muscles or joints 0____________________________________10

14. Low back or shoulder pain 0____________________________________10

15. All the symptoms for the clinical assessment are non-specific without any clinical illness toaccount for.

16. Numbness 0____________________________________10

607

17. Tremors 0____________________________________10

18. Sleep Abnormality 0____________________________________10

19. Loss of Appetite 0____________________________________10



If yes, Present specify______________________________________________________






Continuing 1

Drop out 2 Reason: _____________________________

Died 3 Cause: ______________________________

PHYSIOLOGICAL PARAMETERS

24. Systolic blood pressure (mm of Hg) __________________

25. Diastolic blood pressure (mm of Hg) __________________

26. Upper mid arm circumferences (cm) __________________

27. Chest circumference (cm) __________________

Hand Grip

28. Left Hand (kg) __________________

29. Right Hand (kg) __________________

30. Weight (kg) __________________

608

31. Seated Stature (cm) __________________

32. Biacromial Diameter(cm) __________________

33. Skin fold thickness (mm) __________________

34. Pulmonary Function

FEV (L)_______ PEFR (L) ______ RV (L) ______ FVC (L) ______

Date: ______________ Signature of the Investigator: ________________

609




(0, 15, 30, 45, 60, 75, 90 days)

1. Centre : ...................................



4. Subject Name : ....................................................................................................................



7. Address : Permanent postal Address with phone number and email if any.

..............................................................................................................................................

..............................................................................................................................................

ADVERSE EVENTS

1. Does the patient have any symptoms with medication in trial group ? Yes No.


1 2 3 4

AdverseExperience

Date started

610

Date

Time

Date stopped

Pattern

Isolated-1

Intermittent-2

Continuous-3

Severity

Mild-1

Moderate-2

Severe-3


Serious*

Yes-1

No-2


Relationship to studymedication

Unrelated-1

Possible-2

Probable-3

611

Unrelated: A reaction that does not follow a reasonable temporal sequence from theadministration of the drug; or a known adverse reaction pattern of the suspected drugscould have been produced by the patients clinical stage, intermittent illness, trauma, accidentsetc:



612



(0, 5 week, 6th and 12th month)


1. Centre : ...................................



4. Subject Name : ....................................................................................................................




8. Month Assessment : Initial 0 Ist month 1

6th month 2 12th month 3






11. TC (Cells/Cmm.)_____________________

12. DC: P (%)_______ L (%) _______ E (%)______ M (%)______ B (%) _______

13. Hb (g/dl) _______________

14. ESR (1st hour.)(mm) _______________

15. PCV (%) _______________

613

16. Blood Sugar – PP(mg./dl) _______________

17. S. Cholesterol (mg./dl) _______________

18. HDL (mg./dl) _______________

19. LDL (mg./dl) _______________


21. B. Urea (mg./dl) _______________


23. Uric acid (mg./dl) _______________


25. Albumin (gm./dl) _______________

26. Globulin (gm./dl) _______________

27. A/G Ratio _______________

28. Immunoglobulin levels (gm/dl)

Ig.G. _______ Ig. M. ________ Ig. A.__________

29. Acid Phosphatase (KA units) _______________

30. Alk. Phosphatase (KA units) _______________

31. Hair melanin content (gm%) _______________

32. Nail calcium (mg/100mg) _______________

33. E.C.G.: _________________________________________________________________

34. X-ray Chest: [ 0 Month only ] ______________________________________________

35. X-ray one knee joint [ 0 & 12th Month only ] ________________________________

36. Any other Remarks _______________________________________________________


614

Blank

REPRODUCTIVE SYSTEM

SEC

TIO

N - X

616

Blank

617

Drug: Study Code:


MULTICENTRIC DOUBLE BLIND CLINICAL TRIALOF AYURVEDIC HERBAL FORMULATION IN THE

TREATMENT OF MENOPAUSAL SYNDROME


618

Blank

619

I. BACKGROUND

At Menopause, ovarian estrogen and progestogen production fall to low levels, which insome women are associated with a series of signs and symptoms and physiological consequencesof sex steroid deficiency. Deficiency of estrogens may result in vasomotor manifestations such ashot flushes, perspiration, palpitation and headache. The women may also suffer from urogenitalsymptoms such as vaginal itching, vaginal dryness and psychological symptoms such as irritabilitydepression and insomnia. The symptoms described above are known as Menopausal Syndrome.Available treatment modalities in Western System of Medicine have some limitations in offering acomprehensive satisfactory solution to the problem. Hence there is always search for safe andeffective treatment modality which does not require expensive monitoring system besides bettercompliance to the subjects1.

II. OBJECTIVE

To assess the efficacy of an Ayurvedic formulation in the management of MenopausalSyndrome.

III. CENTRES



Sample Size: 100 patients at each Centre, 50 control and 50 trial cases



MULTICENTRIC DOUBLE BLIND CLINICAL TRIAL OF AYURVEDICHERBAL FORMULATION IN THE TREATMENT OF MENOPAUSAL

SYNDROME

References

1. Dr. Nirmala Joshi (1999) Ayurvedic concept in Gynaecology,) 2nd Edition (1999), Published byChaukabha Sanskrita Pratisthana, Delhi, India.

2. Dr. P.V. Tiwari (1990) Stri Roga Part II 1st Edition Chaukhamba Orientalia, Delhi.

3. Dr. D.C. Dutta, Text book of Gynaecology, 5th Edition2009, Published by New central bookagency, Delhi

620

Drug – Aswagandha, Madhuyasti, Balamula, Saunf,Tila-50mg each and Jayanati beeja-100mg

Dosage – 700mg –twice a day

Duration – 6 months

Design of the study – Randomized Double – blind Placebo controlled study

Duration of the study- 6 months drug therapy with a follow up for 3 months withoutdrug

Total period of study - 9 months. Total duration will be three years to complete the trialat each Centre.

Follow – Up: One follow-up will be carried out after three months of the completion oftreatment



2. History of amenorrhoea for not less than 6 months

3. Score of 10 or more as per the CCRAS scoring of Menopasual Syndrome.


1. Age: Less than 40 years and more than 55 years

2. CCRAS Menopausal score less than 10

3. Organic lesions like tuberculosis, STD, Cancer, Liver and Kidney diseases

4. Surgical menopause

5. Established cases of any mental illness


7. Unexplained uterine bleeding



A patient may be withdrawn from the trial on account of the following

1. Development of any major ailment, side effects necessitating institution of new modalities oftreatment.

2. Worsening of symptoms.

621

3. Patient’s failure to report for follow-up or irregular medication [Missing 10 or Moredoses]


The full details of history and physical examination of the patients will be recorded as perthe proforma (Forms I & IA). Clinical assessment will be done before drug administration, at theend of 1st month, 2nd, 3rd, 4th, 5th and 6th month during treatment and at the end of 3rdmonth follow up (Form II). The laboratory investigations i.e. Urine Examination, Stoolexamination, TC, DC (P, L, E, M, B), Hb%, ESR (1st hour), PCV, Blood Sugar (PP), LipidProfile, B. Urea, S. Creatinine, Uric acid, Total proteins, S. Albumin, S. Globulin, A/G Ratio,SGOT, SGPT, Pap Smear, Thyroid function tests (T3,T4,TSH) LH, FSH Prolactin, X-Ray Chest,Transe Vaginal Sonography will be recorded before drug administration, at the end of treatmentand at the end of follow-up. [Form-III]



X. CLINICAL ASSESSMENT

List of Clinical Symptoms to be taken into account for assessment of the effect of thetreatment of Menopausal Syndrome.

SYMPTOMS SCORE

1. Hot flushes 5

2. Night Sweating 5

3. Insomnia 3

4. Muscle/Joint pain 3

5. Anxiety 2

6. Mood fluctuation 2

7. Irritability 2

8. Dryness/itching in Vagina 3

9. Altered sexual desire 1

10. Fatigue 2

11. Stress incontinence 2

Total 29

622


The progress of the trial will be monitored by field visits by Monitoring Unit of CCRAS.And under Guidance of the Clinical Trial Monitor. Data analysis will be undertaken at theMonitoring Unit of CCRAS.

XII. ETHICAL REVIEW

Each participating centre’s Institutional Ethical Committee (IEC) or Head of the Institutionshould give clearance certificate before the project is initiated. Patient’s information sheet andinformed consent form should be submitted alongwith project proposal for approval by IEC/ Headof the Institution. Both should be maintained in duplicate with one copy given to the patient at thetime of entry to the trial.


A consolidated amount of Rs…….../- per visit will be paid to subject.





623



SYNDROME




Date: _______________ Signature Investigator ______________

Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial of _______________________ on the Menopausal Syndrome.





Relationship ___________________________________


624



SYNDROME



Ayurveda has laid emphasis on maintenance of positive health and prevention of diseases,besides management/treatment of diseases. The present study is aimed to evaluate selectedAyurvedic drugs for their efficacy in the management of menopausal syndrome. You are invited toparticipate in this study where you will be provided a combination of Aswagandha, Madhuyasti,Balamula, Saunf, Tila and Jayanti beeja This formulation will be given to you in the dose of 700mgtwice daily. Classical Texts of Ayurveda prescribe use of these drugs in various Gynecologicaldisorders. The previous observations in clinical and experimental studies have shown promisingeffect of these drugs in the management of menopausal syndrome. About 300 healthy women fromthis and other hospitals around the country will be taking part in this study.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 36 weeks to complete (24 weeks fortreatment and another 12 weeks for follow-up study). During this period, you are expected to visitthe hospital eight times. The interval between the first and subsequent visits during the six monthof treatment will be four weeks. After completion of treatment, status of Health will be monitoredfor next three month after which you will be required to visit the hospital for necessary check up

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination. An X-ray, Blood and urine samples will also be taken. This is to make surethat you are eligible for the study.

If you are found eligible, you would be put on trial treatment for 24 weeks. At each visit,you will be supplied with sufficient quantities of drugs to last until your next visit.


625



SYNDROME


BEFORE TREATMENT


1. Centre : ...................................


3. Subject Name : ....................................................................................................................



6. Address : ..............................................................................................................................



2. History of amenorrhea for not less than 6 months

3. CCRAS Menopausal Syndrome Score>=10.



5. History of amenorrhea <6 months

6. Organic lesions like tuberculosis, STD,

7. Cancer, Liver and Kidney diseases

8. CCRAS Menopausal score < 10

9. Surgical menopause

626

10. Established cases of mental disorder


12. Unexplained uterine bleeding




If admitted, Sr. No. of the Subject: ____________________________________________

No. of packets issued: ____________________________________________

Date: ___________ Signature of the Investigator: ___________________

627



SYNDROME



1. Centre : ...................................



4. Subject Name : ....................................................................................................................



7. Address : ..............................................................................................................................








Constant sitting/standing for long hour


10. Family income per month in Rs. : ........................................................................................

11. Total family members : .........................................................................................................

628

12. Marital status: Single Married Separated

Window Widower


Living alone

Living with spouse/nuclear

Living in joint family

Others (specify)

Chief complaint with duration in weeks (If any) Absent (0) Present (1) Duration

14. Hot flushes

15. Night Sweating

16. Insomnia

17. Muscle/Joint pain

18. Anxiety

19. Mood fluctuation

20. Irritability

21. Dryness/itching in vagina

22. Altered sexual desire

23. Fatigue

24. Stress incontinence

25. Other complaints

If any, specify: ___________________________________________________________

26. History of serious illness in the past (if any): ____________________________________

629

Personal History

27. Diet Veg. 1 Non-Veg. 2 Lacto-Ova Veg. 3

28. Sleep Good. 1 Disturbed 2 Insomnia 3


30. Bowel habit Regular 1 Constipation 2 Hard Stool 3

Loose Stool 4

Addiction

31. Smoking Yes 1 No 2

If yes specify: (a) Quantity [packs]: ________________


32. Tobacco Yes 1 No 2

If yes specify: (a) Quantity: ________________


33. Alcohol Yes 1 No 2

If yes specify: (a) Quantity (in ml/day): ________________


34. Any other (specify) _______________________________________________________

Menstrual History:

35. Age in years at Menarche

36. Duration of menstrual period in days

37. Interval of menstrual period

38. Age in years at onset of menopause

630

Obstetrics History:

39. Age at marriage

40. Parity (Number of Live births)

41. Duration in years since last delivery


Vata-Kaphaj Vata-Pittaja Pittaj-Kaphaja

Sannipataj


43. Height (cm) ____________

44. Weight (kg) ____________

45. Pulse (per min) ____________

46. Blood Pressure Systolic (mm Hg)____________

47. Blood Pressure Diastolic (mm Hg)____________



49. Pallor

50. Hirsutism

51. Lymphadenopathy

If present, specify

General Local Area: ______________________


52. CVS

If abnormal details________________________________________________________

631



54. CNS






57. Per vaginal examination

If abnormal, details________________________________________________________

58. Breast examination


59. Pap smear


Date: ____________ Signature of Investigator: ___________________

632



SYNDROME

FORM III – CLINICAL ASSESSMENT

(0, 1, 2, 3, 4, 5, 6 & 9th Month)

1. Centre : ...................................



4. Subject Name : ....................................................................................................................





9. Address : ..............................................................................................................................

Clinical Symptoms Abscent (0) Present (1)

10. Hot flushes

11. Night Sweating

12. Insomnia

13. Muscle/Joint pain

14. Anxiety

15. Mood fluctuation

16. Irritability

17. Dryness/itching in vagina

633

18. Altered sexual desire

19. Fatigue

20. Stress incontinence

21. Other complaints, if any (Specify) ____________________________________________

22. Adverse reaction: No 0 Yes 1

If yes, details:____________________________________________________________


Improved No change 2 Deteriorated 3


Complete Cure Improved 2 No Change 3

Deteriorated


Continuing

Drop out Reason:_____________________________

Died 3 Cause:_______________________________

Date: ______________ Signature of the investigator: ________________

634



SYNDROME


(0, 1, 2, 3, 4, 5, 6 & 9th Month)

1. Name of the Subject: ………………………………………….......................……....…

2. Address ……………………………………………………………..............…………..

3. Sr. No. of the subject:

4. Centre…………………………


6. Sex: Male (1) Female (2)

7. Date of Birth: Age (in yrs.):

8. Date of admission: Date of discharged:

9. Address : ................................................................................................................................

ADVERSE EVENTS

1. Does the patient have any symptoms with medication in trial group? Yes No


1 2 3 4

Adverse

Experience

635

Date started

Date

Time

Date stopped

Pattern

Isolated-1

Intermittent-2

Continuous-3

Severity

Mild-1

Moderate-2

Severe-3



Serious*

Yes-1

No-2





636

Relationship

to study

medication

Unrelated-1

Possible-2

Probable-3










637



SYNDROME


( 0, 6th AND 9th MONTH)

1. Centre : ...................................



4. Subject Name : ....................................................................................................................




8. Address : ..............................................................................................................................

9. Month Assessment : Initial 0 6th month 1

9th month 2






12. TC (Cells/Cmm.)_____________________

13. DC: P (%) ______ L (%) ______ E (%) ______ M (%) _______ B (%) _______

14. Hb (g/dl) _________________

638

15. ESR (1st hour.) (mm) _________________

16. PCV (%) _________________

17. Sugar – PP(mg./dl) _________________

18. S. Cholesterol (mg./dl _________________

19. HDL (mg./dl) _________________

20. LDL (mg./dl) _________________

21. S. Triglycerides (mg./dl) _________________

22. B. Urea (mg./dl) _________________

23. S. Creatinine (mg./dl) _________________

24. Uric acid (mg./dl) _________________

25. Total proteins (gm./dl) _________________

26. Albumin (gm./dl) _________________

27. Globulin (gm./dl) _________________

28. A/G Ratio _________________

29. SGOT _________________

30. SGPT _________________

The tests from S. No. 31 to 36 will be carried out only once at 0 month.

Thyroid Function test

31. T3 (n mol/L) __________________________________

32. T4 (ug/dL) __________________________________

33. TSH (mU/L) __________________________________

34. LH (IU/L) __________________________________

35. FSH (IU/L) __________________________________

639

36. Prolactin (ug/L) __________________________________

37. Trans Vaginal Sonograph __________________________________

38. Pap smear __________________________________

39. X-ray Chest: [0 Month only ] ______________________________

40. Any other Remarks __________________________________

PHYSIOLOGICAL PARAMETERS

41. Systolic blood pressure(mm of Hg) __________________

42. Diastolic blood pressure(mm of Hg) __________________

43. Weight (kg) __________________

Date: _____________ Signature of the investigator: ________________

640



SYNDROME

CASE RECORD FORM – V RECORD OF UNSCHEDULED VISITS OF THEPATIENT

1. Centre : ...................................



4. Subject Name : ....................................................................................................................



7. Date of unscheduled visit :

8. Address : ..............................................................................................................................

9. Summary of treatment given : ..............................................................................................................................................................................................................................................................................

Date: _____________ Signature of the investigator: ________________

641

Drug: Study Code:


TO STUDY THE EFFICACY OF AYURVEDICFORMULATION IN THE TREATMENT OFDYSFUNCTIONAL UTERINE BLEEDING


642

Blank

643

I. BACKGROUND

Dysfunctional Uterine Bleeding (DUB) is excessive or prolonged bleeding during menstrualperiod. In addition, it also includes the menstruation with short inter menstrual period, for which nodemonstrable cause is found. Though no active reproductive age is exempt, the disease is mostlyfound in early puberty and or late reproductive life (peri-menopausal period). Modern Medicinedoes not have a permanent cure and most of the time patients have to opt for hysterectomy.Rakta Pradara or Asragdhara mentioned in Ayurved is a broad term which covers all sorts ofexcessive uterine bleeding. For the present study, exclusively dysfunctional uterine bleeding hasbeen taken up. Ayurvedic system is having many effective remedies for this problem. Among themthe combination of Ashoka- 100mg., Lodhra –50mg., Nagakeshara-50mg.,Doorva-100mg areselected for the present study. The previous observations in clinical and experimental studies haveshown promising effect of these drugs in the management of DUB.

II. OBJECTIVE

To assess the efficacy of an Ayurvedic formulation in the management of DysfunctionalUterine Bleeding (DUB).

III. CENTRES

CCRAS identified Centres.



Treatment : Two capsule of 300mg each containing Ashoka andDoorva (two parts each), Lodhra and Nagakeshara (onepart each) twice a day, for three months.

Duration : 3 months.


Duration of the study : Three months drug therapy with follow up for six months.Total period of study will be nine months for each case.

Period of Study : 9 months for each case. Total duration will be three yearsto complete the trial at each Centre.


PROTOCOL TO STUDY THE EFFICACY OF AYURVEDIC FORMULATION INTHE TREATMENT OF DYSFUNCTIONAL UTERINE BLEEDING

644

Follow – Up : Two follow-ups will be carried out after three and sixmonth of the completion of treatment.


1. Age: between menarche and menopause

2. Excessive bleeding during menstruation (change of more than 5 soiled pads in a day)

3. Passing of large clots

4. Prolonged menstrual bleeding (more than 7 days)

5. Excessive bleeding for more than 2 consecutive cycles


1. Blood dyscrasias

2. Intrauterine growth such as myoma, endometrial polyp etc.

3. Cancer of cervix and or uterus

4. Hb% less than 7 gm.

5. Endocrinal disorders

6. Any other systemic disorders likely to influence menstrual cycle

7. Case undergoing treatment for any other serious illness.


The patients will be withdrawn from the study

1. If the condition worsens

2. Development of any other serious disease

3. Patient’s failure to report for follow-up or irregular medication [Missing 10 or More Doses]

The cases withdrawn from the study will be managed by the Investigator


The full details of history and physical examination of the patients will be recorded as perthe proforma (Forms I & IA). Clinical assessment will be done before drug administration, at theend of 1st, 2nd and 3rd month, during treatment and at the end of 6th and 9th month during followup (Form II). Required laboratory investigations will be carried out to exclude cases as specifiedin the criteria for exclusion (Form-III).

645

IX. CRITERIA FOR ASSESSMENT OF RESULTS

Reduction in menstrual flow (i.e. decrease in use of soiled pads (three or less) in a day),total stoppage of passing of large clots and reduction in menstrual bleeding period to 7 days orless will be considered as significant improvement.


Data on number of pads used, duration of flow of menstrual period and Disappearance oflarge clots will be tabulated and analyzed using appropriate statistical methods.


The progress of the trial will be monitored by field visits by Monitoring Unit of CCRAS.Data analysis will be undertaken at the Monitoring Unit of CCRAS.

XII. ETHICAL REVIEW


B. Data and Safety Monitoring Board: A Data and safety monitoring board (DSMB) atHqrs will carefully monitor the data and side effects during the period of study and put ina place where by prompt reporting of adverse events occur. The data will be reviewed asevery 20 participants entered the study and administered the trial drugs. The research teamwill report immediately to the PI and Data Monitoring Board for any life threateningconditions whether they are perceived to be study related or not. The Board decideswhether the adverse effects warrant discontinuation of the study protocol. Protocols will bewritten and approved for the treatment of study related adverse events


A consolidated amount of Rs. ______ per visit will be paid to subject put on treatment.


Short-term two-day training will be provided to the Investigators and Laboratorypersonnel involved in the trial at CCRAS Hqrs. The investigators and technicians will be detailedabout the clinical trial conduct and laboratory procedures in order to maintain the uniformity.



646


CLINICAL STUDY TO STUDY THE EFFICACY OF AYURVEDICFORMULATION IN THE TREATMENT OF DYSFUNCTIONAL UTERINE

BLEEDING





Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial assessment of the effect of Ayurvedic formulation in the treatment ofdysfunctional uterine bleeding.





Relationship ___________________________________


647



BLEEDING



Dysfunctional Uterine Bleeding (DUB) is excessive or prolonged bleeding during menstrualperiod, for which no demonstrable cause is found. Ayurveda is having many effective remedies forthis problem. A formulation containing Ashoka and Doorva (two parts each), Lodhra andNagakeshara (one part each) have been selected for the present study.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take nine months to complete (three months for treatmentand another six months for follow-up study). During this period, you are expected to visit thehospital eight times. The interval between the first and subsequent visits during the three months oftreatment will be one month. After completion of treatment, status of health will be monitored fornext six months during which you will be required to visit the hospital for necessary check up afterthree and six months.

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination. An ultra sound will be done and Blood and urine samples will also be taken.This is to make sure that you are eligible for the study.

If you are found eligible, you would be put on trial treatment for 6 months. Ateach visit, you will be supplied with sufficient quantities of drugs to last until your nextvisit.


648



BLEEDING


1. Centre : ...................................


3. Subject Name : ....................................................................................................................



6. Address : ..............................................................................................................................


1. Age: between menarche and menopause

2. Excessive bleeding during menstruation (use of more than five soiled pads)


4. Prolonged menstrual bleeding (more than seven days)


5. Blood dyscrasias

6. Intrauterine growths

7. Cancer of cervix and or uterus

8. Hb% < 7 gms.

9. Endocrinal disorders

10. Any other systemic disorders likely to influence menstrual cycle

649

11. Case undergoing treatment or any other serious illness_____________________________


If Sl. No. 1 – 47 is ‘Yes’ and Sl. No.5 – 16 are ‘No’

If admitted, Sr. No. of the subject: _____________________

No. of packets issued: ______________________________

Dated: ____________ Signature of the Investigator: _____________________

650



SYNDROME



1. Centre : ...................................



4. Subject Name : ....................................................................................................................



7. Address : ..............................................................................................................................








Constant sitting/standing for long hour 5


10. Family income per month in Rs. : ........................................................................................

11. Total family members : .........................................................................................................

651

Chief complaint with duration in months Absent (0) Present (1) Duration

12. Excessive bleeding during menstruation

If present, indicate since when (in months) _____________________________________

Number of soiled pads being used per day ____________________________________


If present since when (months)_______________________________________________

Number of clots per day___________________________________________________

14. Prolonged menstrual (more than seven days)

If present since when (months) ______________________________________________

Duration of bleeding in days_________________________________________________

Pain during Menses________________________________________________________

15. Other complaints, if any (Specify with duration) _________________________________

Personal History

16. Diet: Veg. 1 Non-veg 2

17. Bowel habits Regular 1 Irregular 2

Past Menstrual History:

18. Age at Menarche (in years)

19. Average length of menstrual cycle in days

20. Duration of bleeding period in days

21. Amount of bleeding per day (in pads)

22. Associated symptoms if any_________________________________________________

21. History of excessive bleeding in the past: Yes 1 No 2

If yes give details including treatment received: __________________________________________________________________

652

Obstetric History:

22. Marital status: Unmarried 1 Married 2 Widow 3

Divorce/ 4Separated

If married Age at marriage (In years):

23. Total no. of pregnancies

24. H/o difficult labour

25. No. of living children

26. Total no. of Abortion/still birth if any

27. Age of last child (in years)

28. Current Contraceptive use if any

None IUD Condom Vasectomy

Natural Pills Female sterilization

29. Prakriti (Pl. see separate sheet attached):



Sannipataja 7


30. Pulse (per min) ____________

31. Blood Pressure Systolic (mm Hg) ____________

32. Blood Pressure Diastolic (mm Hg) ____________


653


34. Hirsutism

35. Lymphadenopathy

If present, specify the area__________________________________________________

Local 1 General 2 Area __________________________________


36. CVS




38. CNS






PER VAGINAL EXAMINATION (only in married woman)

41. Uterine size: Normal 1 Enlarged 2

If enlarged, size in cms. ____________________________________________________

42. Uterine mobility: Free 1 Restricted 2 Fixed 3

43. Uterine tenderness Yes 1 No 2

44. Adnexa Normal 1 Thickened and tender 2

45. Adnexal mass Absent 1 Present 2

46. Tenderness in lower abdomen Yes 1 No 2

654

47. PER SPECULUM EXAMINATION (only in married woman)

Normal 1 Abnormal 2

If Abnormal, Specify_______________________________________________________

Cervical examination Normal (1) Abnormal (0)

48. Cervicitis

49. Erosion

50. Mucous discharge

51. Polyp

52. Ectropion of Others_______________________________________________________

53. Breast examination


Dated: ________________ Signature of Investigator: ___________________

655



BLEEDING

CASE REPORT FORM III – CLINICAL ASSESMENT

(0, 1st, 2nd, 3rd, 6th and 9th Month)

1. Centre : ...................................



4. Subject Name : ....................................................................................................................




8. Month of Assessment : Initial 1st month 2nd month

3rd month (3) 6th month 9th month

9. Address : ..............................................................................................................................

Clinical Symptoms Abscent (0) Present (1)

10. Excessive bleeding during menstruation

If present number of pads used per day_______________________________________


12. Prolonged menstrual bleeding

If present duration of MF in days____________________________________________

13. Pain during menses Yes 1 No 2

14. Other complaints, if any (Specify)_____________________________________________

656


Continuing (1)

Drop out (2) Reason:______________________________

Died (3) Cause:_______________________________

.Date: ______________ Signature of the Investigator ________________

657



BLEEDING

CASE REPORT FORM IV– LABORATORY INVESTIGATIONS PARAMETERS

(For exclusion of cases at the time of screening)

1. Centre : ...................................



4. Subject Name : ....................................................................................................................




8. Month of Assessment : Initial 1st month 2nd month

3rd month (3) 6th month 9th month


Routine ____________________ Microscopic___________________________

11. TC (Cells/Cmm)___________________________________________________

12. DC: P (%) ______ P (%) ______ P (%) ______ P (%) ______ P (%) ______

13. Hb (g/dl) ______________

14. ESR (1st hour.) (mm) ______________

15. Bleeding time ______________

Dated: ________________ Signature of Investigator/___________________

658

(Investigations from Sl.No.16 to 24 will be done initially only)

16. Clotting time: ____________________________

17. Prothrombin Time: ____________________________

18. Fibrinogen count: ____________________________

19. PCV (%): ____________________________

20. Blood Sugar – PP (mg./dl): ____________________________

21. B. Urea (mg./dl): ____________________________

22. S. Creatinine (mg./dl): ____________________________

23. Thyroid function tests: ____________________________

i. T3 ____________________________

ii. T4 ____________________________

iii. TSH ____________________________

iv. LH ____________________________

v. FSH ____________________________

24. Transe Vaginal Sonography ___________________________________________

25. Any other Remarks ___________________________________________

Date: _____________ Signature of Investigator: _________________________

659

Drug: Study Code:


MULTICENTRIC OPEN CLINICAL TRIAL OFRAJAHPRAVARTINI VATI IN KASHTARTAVA

(DYSMENORRHOEA)


660

Blank

661

I. BACKGROUND

Dysmenorrhoea (Kashtarthava/udavarta)1 is characterized by severe pelvicpain occurring before or during the menstruation. Headache, nausea, vomiting,diarrhoea, lethargy, dizziness, sweating, breast tenderness, tachycardia and heavymenstrual flow may accompany this pain. It is classified into two, primary andsecondary dysmenorrhoea. Primary Dysmenorrhoea has no organic cause, starts usuallyduring teenage years and coincides with the onset of ovulatory cycles. An overall 75%of women develop Primary Dysmenorrhoea of them 15% may have severe symptoms.Secondary Dysmenorrhoea usually arises in later reproductive age and usually is theresult of pelvic pathology.

Woman with primary dysmenorrhoea usually has regular menstrual cycles with symptomsbeginning just prior to menstruation. In the patients of dysmenorrhoea uterine contraction pressureand resting tone are increased. The pain is thought to be secondary to ischemia due to reductionin blood flow, which accompanies the contractions.

Secondary Dysmenorrhoea result from pelvic pathology and can occur at any ageafter menarche and before menopause. Cervical Stenosis, Endometriosis, Pelvic infections,Pelvic congestion, intrauterine birth control devices etc. can cause secondaryDysmenorrhoea.


MULTICENTRIC OPEN CLINICAL TRIAL OF RAJAHPRAVARTINI VATI INKASHTARTAVA (DYSMENORRHOEA)

References

1. Ambikadutta Shastri, 1972, Sushruta Samhita, Ayurveda tatwa pradeepika, Hindi Commentary,Chowkamba Sanskrita Series, Varanasi.

2. Priyavat Sharma - Dravyaguna Vignana, Chowkamba Sanskrita Series, Varanasi.

3. Vagbhata, 1976 Astanga Samgraha, Sutra sthana, Telugu Academy, Hyderabad.

4. Ayurvedic formulary of India, Part-1, Department of AYUSH, Ministry of Health & FamilyWelfare, Government of India

662

In Ayurveda, the cardinal feature of Udavartha Yonivyvapath is said as pain duringmenstruation. Based on the cardinal feature and other associated features like low backpain,relief from pain after discharge of menstrual blood clot etc, this can be compared withprimary or secondary dysmenorrhoea. For the present study primary dysmenorrhoeacases only will be included. To regulate uterine contractions and uterine tone manyeffective Ayurvedic regimen are described in Ayurvedic classics. On clinical andexperimental studies these drugs are also found effective. For the present studyRajahpravartini vati, a well known and safe classical Ayurvedic drug has taken upfor the study.

Owing to the gravity of the situation, need is felt for search of safe/effective Ayurvedic oraldosage forms to reduce pain during menstrual period. Keeping the gravity of the situation and thepublic health needs in view, the council intends to initiate scientific studies on well known and safeclassical Ayurvedic formulation Rajahpravartini vati, which is being successfully prescribed byAyurvedic physicians without any side effects since centuries. The formulation has beenstandardized after formulating SOPs besides safety / toxicity evaluation.

The objective of current study is to assess clinical safety and efficacy through measurableobjective parameters.

II. OBJECTIVES

1) To observe the effect of Rajahpravartini vati in the management of menstrual pain ofdysmenorrohoea subjects.

2) Observe the clinical safety of on Rajahpravartini vati in dysmenorrohoea Subjects

III. CENTRES

CCRAS Institutes



Trial Drug /Dosage /Duration : Rajahpravartini vati 250 mg. (tablet) twicedaily after meal with warm water for 90days (for three consecutive cycles)

663

The drug will be started from 5th day ofthe menstrual cycle

Design of the Study : Open trial

Total period of the study : 1 year (recruitment of Subjects upto theend of 6th month, continuation of trialtherapy till end of 8th month, last 4months for compilation of data andstatistical analysis)


1. Age between 16-35 years.

2. Painful menstruation for at least 3 consecutive cycles with regular menstrual cycles havingnormal bleeding phase. (21- 35 days is the normal menstrual cycle)

3. Not associated with any organic Reproductive system abnormalities (Excluded clinicallyand Radiological)


1. Cases of Secondary dysmenorrhoea

2. Pain abdomen associated with Excessive Bleeding Per vagina

3. Associated with leomyoma (Fibroid) of Uterus, Ovarian Cyst, Endometriosis (ExcludedClinically and Radiological)

4. Associated with pelvic inflammatory disease, Hydrosalpinx (Excluded Clinically andRadiological)

5. Associated with any serious systemic disorders likely to influence menstrual cycle

6. History of malignancy of pelvic organs

7. History of Hypo and Hyper Thyroidism

8. Women using an IUD/ Oral Contraceptive Pills (OCP)


10. Hypertension


During the course of the trial treatment, if any serious condition or any serious adverseevents which requires urgent treatment or if patients herself want to withdraw from the study, suchsubjects may be withdrawn from the trial.

664


The full details of screening, history and physical examination of the subjects will berecorded as per case record form I & II. Clinical, physiological and Laboratory assessment inform III at 0, 30th (5th day of menstruation), 60th (5th day of menstruation) and 90th day (5th dayof menstruation) and laboratory investigations in forms IV will be done at 0 and 90th days.


The changes in the subjective and objective parameters before and after the treatment shallbe considered for assessment of the safety and efficacy the drug. The safety parameters (liver andkidney function) will be assessed at 0 and 90th day.




The progress of the trial will be monitored by field visits by monitoring unit of CCRAS.Data analysis will be undertaken at the Monitoring Unit of CCRAS.


A. Institutional Ethical Committee (IEC): The proposal will be placed before Institutional EthicalCommittee (IEC) of trial center for getting clearance certificate before the project isinitiated. Patient’s information sheet and informed consent form will be submitted alongwith project proposal for approval by IEC.

B. Data and safety monitoring board: A Data and safety monitoring board (DSMB) at Hqrswill carefully monitor the data and side effects during the period of study and put in aplace where by prompt reporting of adverse events occur and take appropriate steps incase of any adverse events occur. The data will be reviewed for every 20 participantsincluded into the study and administered the trial drugs. The research team will reportimmediately to the PI and Data Monitoring Board for any life threatening conditionswhether they are perceived to be study related or not. The Board decides whether theadverse effects warrant discontinuation of the study protocol. Protocols will be written andapproved for the treatment of study related adverse events


A consolidated amount of -------- per visit i.e., on the 1st day of recruitment afterscreening, 1st, 2nd, 3rd month (4 times)

665




The Laboratory Investigations (Haematological /Biochemical, etc.), which are not availableat research Institutes should be conducted at identified reputed labs /Government Institutes underintimation to this Council following codal formalities.

666






Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “MULTICENTRIC OPEN CLINICAL TRIAL OFRAJAHPRAVARTINI VATI IN KASHTARTAVA (DYSMENORRHOEA)”





Relationship ___________________________________


667





Dysmenorrhoea is characterized by severe pelvic pain occurring before or during themenstruation. Headache, nausea, vomiting, diarrhoea, lethargy, dizziness, sweating, breasttenderness, tachycardia and heavy menstrual flow may accompany this pain. It is classified intotwo, primary and secondary dysmenorrhoea. Primary Dysmenorrhoea has no organic cause, startsusually during teenage years and coincides with the onset of ovulatory cycles. An overall 75% ofwomen develop Primary Dysmenorrhoea of them 15% may have severe symptoms. SecondaryDysmenorrhoea usually arises in later reproductive age and usually is the result of pelvic pathology.

In conventional medicine various forms of pain killers and anti spasmodic drugs arecommonly prescribed, but these therapies have their noted adverse effects e.g. nausea, vomitting,abdominal pain.

Owing to the gravity of the situation, need is felt for search of safe/effective Ayurvedic oraldosage forms to reduce pain during menstrual period. Keeping the gravity of the situation and thepublic health needs in view, the council has initiated scientific studies on Rajahpravardhini vati, apromising formulation that is being successfully prescribed by Ayurvedic physicians without any sideeffects since centuries. The formulation has been standardized after formulating SOPs besides safety/ toxicity evaluation.

The objective of current study is to assess clinical safety and efficacy through measurableobjective parameters.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 3 months during treatment period, youare expected to visit the hospital 3 times i.e. on 0, 1st, 2nd, 3rd month for clinical and physiologicalassessment.



At each visit, you will be supplied with sufficient quantities of drugs to last until your nextvisit. If any adverse reactions like skin allergy, nausea, vomiting and palpitation/tremor etc., noticedduring the treatment period, this should be noticed to the Principle Investigator.


668




BEFORE TREATMENT


1. Centre : ...................................


3. Subject Name : ....................................................................................................................


5. Address : Permanent postal address with phone number & E-mail if any.

..............................................................................................................................

..............................................................................................................................


6. Age between 16-35 years.

7. Painful menstruation for at least 3 consecutive cycles with regular menstrual cycles having normal bleeding phase.

8. (21- 35 days is the normal menstrual cycle) abnormalities (Excluded Clinically and Radiological)

9. Not associated with any organic Reproductive system

CRITERIA OF EXCLUSION Yes (1) No (2)

10. Cases of secondary Dysmenorrhoea

11. Pain abdomen associated with Excessive BPV

12. Associated with leomyoma of Uterus, Ovarian Cyst, Endometriosis (Excluded Clinically and Radiological)

669

13. Assoicated with pelvic inflammatory disease, Hydrosalpinx

14. Associated with any serious systemic disorders likely to influence menstrual cycle

15. History of malignancy of pelvic organs

16. History of Hypo and Hyper thyroidisam

17. Women using an IUD/ Oral Contraceptive Pills (OCP)


19. Hypertension

Whether the subject is suitable for enrollment? YES NO

(A subject is suitable for enrollment in the trial, if points 6 to 9 are YES and points 10to 19 are NO)

If enrolled:-

Subject Sl. No.: ___________ No. of strips issued_________________

Date: ___________________

20. Irregular follow-up

21. Not 100% compliance with treatment

22. Developing any other serious illness during treatment

If ‘Yes’ to 6 – 9 and ‘No’ to 10 – 19 above, recruit the subject for the trial, if recruited, subjectserial No: _ _ _ _ _ _ _ _ _ _ _ _

Date: _________________ Signature of the investigator: ______________________

670





1. Centre : ...................................


3. Subject Name : ....................................................................................................................



..............................................................................................................................

..............................................................................................................................

SOCIO ECONOMIC BACKGROUND:

1). Education:

Husband: 1.Nil 2. Upto Primary 3.Upto middle

4. Upto 10+2 5. College & Above

Wife: 1. Nil 2. Upto Primary 3.Upto middle


2). Occupation: Husband: _______________________ Wife: ________________________

3). Family Income per month in Rs: ______________ Income per capita in Rs: __________

4). Religion: 1. Hindu 2. Muslim 3. Sikh

4. Christian 5. Others

671

5). Working Status: 1. Not gainfully employed 2. Casual worker

3. Own business 4. Regular salaried job

6). MEDICAL HISTORY:

Chronic illness: Allergy:

Surgery: Communicable diseases

7). FAMILY HISTORY:

1). Type of family: Nuclear No. of persons:


2). Diseases: Chronic illness:

Hypertension: Diabetes:

Genetic disorders: specify: ____________________

Psychiatric disorder: Other:

3). History of Multiple births: ___________________________________________________

8). MENSTRUAL HISTORY:

1. Menarche:

2. Menstruation - Duration: Flow:

- Interval: Amount: (Number of pads)

- Passage of clots: yes/no

9). MARITAL HISTORY:

1. Age of marriage: 2. Marital life (in years):

3. Consanguineous: Yes/No

4. Current contraceptive use (If any): IUCD OCP Female sterilization

672

10). PERSONAL HISTORY:

1. Diet: Vegetarian: Non-Vegetarian:

2. Habits: Smoking/Drinking/Chewing Pan/Tobacco:

11). OBSTETRIC HISTORY:

12). HISTORY OF PRESENT COMPLAINTS Yes (1) No (0) Duration(in days)

1. Pain abdomen

2. Low backache

3. Pain in lower limbs

4. Nausea & vomiting

5. Constipation

6. Giddiness

7. Breast tenderness

8. Diarrhoea

9. Headache

10. Fainting

S.N Year Full Pre Post Abortion Type of Baby

term term term Sex Alive Stillborn Weight

673

Medication:

1). Whether received any hormonal treatment previously

2). Any other medication




3. Body weight (Kg.) __________

4. Height (cm)_________

5. Body temperature (oF)____________

6. Blood pressure (in sitting posture of right upper limb) –

7. Systolic _______ mm/Hg

8. Diastolic _______ mm/Hg

9. Pulse rate__________ /min. (Radial pulse of right upper limb)

10. Respiration rate _________ /min.


11. Pallor

12. Koilonychia

13. Lymphadenopathy


14. CVS with chest

If Abnormal, specify abnormalities____________________________________________

15. CNS

If abnormal, specify abnormalities_____________________________________________

674

16. DIGESTIVE SYSTEM



Liver

Spleen

Yes (1) No (0)

Inspection: Incisional Scars:

Over stretching of abdomen:

Prominent veins over the abdomen:

Palpation: Tenderness in lower abdomen:

18. Pelvic Examination

• Inspection – Perineum Vulva:

• Per speculum examination: Vagina:

• (in married woman): Cervix:

• Bimanual examination (in married woman):

Uterus – Size Position Mobility Tenderness

Adnexa – Palpable / Not palpable Tenderness Adnexal mass

17. SAMPRAPTI (PATHOGENESIS) Vata Pitta Kapha

a) Anubandhya dosha

b) Anubandha dosha

c) Avaraka dosha

d) Kasheena dosha

e) Ksheena dhatu Rasa Rakta Mamsa

675

Meda Asthi Majja

Shukra Oja

f) Dushya Rasa Rakta Mamsa

Meda Asthi Majja

Shukra Oja

Date: _____________ Signature of investigator ___________________

Name of investigator ______________________

676



CASE REPORT FORM – III

PERIODICAL OBSERVATION AND CLINICAL ASSESSMENT

(On 0 Day, 5th day of menstruation)


1. Centre : ...................................


3. Subject Name : ....................................................................................................................



..............................................................................................................................

..............................................................................................................................

HISTORY OF PRESENT COMPLAINTS Yes (1) No (0) Duration(in days)

1). Pain abdomen

2). Low backache

3). Pain in lower limbs

4). Nausea & vomiting

5). Constipation

6). Giddiness

7). Breast tenderness

8). Diarrhoea

677

9). Headache

10). Fainting

11) Other associated symptoms

If yes, specify____________________________________________________________

Date: ______________ Signature of investigator ___________________


678



CASE REPORT FORM III


(1st month, 5th day of menstruation)


1. Centre : ...................................


3. Subject Name : ....................................................................................................................



..............................................................................................................................

..............................................................................................................................


1. Pain abdomen

2. Low backache



5. Constipation

6. Giddiness


8. Diarrhoea

679

9. Headache

10. Fainting

11. Other associated symptoms

If yes, specify____________________________________________________________

Adverse reactions: Present Absent


13. Nausea

14. Diarrhoea

15. Skin rashes

16. Any other adverse complaints/ observations specify ______________________________






Continuing (1)

Drop out (2) Reason: _____________________________

Died (3) Cause: _______________________________

If continuing Number of blisters issued _____________________________



680





(2nd month, 5th day of menstruation)


1. Centre : ...................................


3. Subject Name : ....................................................................................................................



..............................................................................................................................

..............................................................................................................................


1. Pain abdomen

2. Low backache



5. Constipation

6. Giddiness


8. Diarrhoea

681

9. Headache

10. Fainting


If yes, specify____________________________________________________________



13. Nausea

14. Diarrhoea

15. Skin rashes







Continuing (1)

Drop out (2) Reason: _____________________________

Died (3) Cause: _______________________________




682





(3rd month, 5th day of menstruation)


1. Centre : ...................................


3. Subject Name : ....................................................................................................................



..............................................................................................................................

..............................................................................................................................


1. Pain abdomen

2. Low backache



5. Constipation

6. Giddiness


8. Diarrhoea

683

9. Headache

10. Fainting


If yes, specify____________________________________________________________



13. Nausea

14. Diarrhoea

15. Skin rashes







Continuing (1)

Drop out (2) Reason: _____________________________

Died (3) Cause: _______________________________




684



(On Day 0)

CASE REPORT FORM – IV PERIODICAL OBSERVATION ANDLABORATORY ASSESSMENT

CCRAS MCT : 09 - 1

1. Centre : ...................................


3. Subject Name : ....................................................................................................................



..............................................................................................................................

..............................................................................................................................


7. Investigations: Blood:

1). Hb%: _____________________

2). ABO Rh: _____________________

3). VDRL _____________________

4). Clotting time _____________________

5). Bleeding time _____________________

6). Prothrombin time _____________________

7). Fibrinogen time _____________________

8). PCV (%) _____________________

685

9). Blood Sugar Fasting/PP _____________________

10). Blood Urea _____________________

11). Serum Creatinine _____________________

12). SGOT _____________________

13). SGPT _____________________

14). Serum Bilirubin _____________________

15). Thyroid profile (T3, T4 and TSH)

16). Serum Cholesterol

17). Urine: Routine: _____________________

Microscopic: _____________________

18). USG _____________________

Date:___________________ Signature of the investigator_________________


686



(On 90th Day)

CASE REPORT FORM – IV PERIODICAL OBSERVATION ANDLABORATORY ASSESSMENT


CCRAS MCT : 09 - 1

1. Centre : ...................................


3. Subject Name : ....................................................................................................................



..............................................................................................................................

..............................................................................................................................



1). Hb%: _____________________

2). ABO Rh: _____________________

3). VDRL _____________________

4). Clotting time _____________________

5). Bleeding time _____________________

6). Prothrombin time _____________________

7). Fibrinogen time _____________________

687

8). PCV (%) _____________________

9). Blood Sugar Fasting/PP _____________________

10). Blood Urea _____________________

11). Serum Creatinine _____________________

12). SGOT _____________________

13). SGPT _____________________

14). Serum Bilirubin _____________________

15). Thyroid profile (T3, T4 and TSH)

16). Serum Cholesterol

17). Urine: Routine: _____________________

Microscopic: _____________________

18).USG _____________________

Date:___________________ Signature of the investigator_________________


688



MULTI CENTRIC OPEN CLINICAL TRIAL OF RAJAHPRAVARTINI VATI INKASHTARTAVA (DYSMENORRHOEA)

(To be translated into local language)



Sl. No. of Participant .................................................................................................................


Please come for next visit on ................................. (Date and time is to be filled by theInvestigator)


• Please take one tablet twice a day after food with a glass of Luke warm water(approx. 250 ml.) maintaining 12 hours gap in between.

• Please return the empty strip after taking medicine along with the compliance reportduly filled.




1.

2.

3.

4.

5.

689

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

690






(To be issued on 2nd visit – 31 day and taken back on 3nd visit –60th day)










1.

2.

3.

4.

5.

691

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

692
















1.

2.

3.

4.

5.

693

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

695





1. Centre : ...................................


3. Patient No. : ............................................................................................................................

4. Name ......................................................................................................................................

5. Sex : Male Female

6. Age (in yrs). ..........................................................................................................................

VISUAL ANALOGUS SCALE FOR PAIN ASSESSMENT

Pain VAS Should be done at base line, each cycle

696





1. Centre : ...................................


3. Patient No. : ............................................................................................................................

4. Name ......................................................................................................................................

5. Sex : Male Female

6. Age (in yrs). ..........................................................................................................................

Sl Subjective/ objective 0 day/BT 1st month 2nd month 3rd month/ATParameters Dt. Dt. Dt. Dt.

7. Pain abdomen

8. Low backache



11. Constipation

12. Giddiness


14. Diarrhoea

15. Headache

16. Fainting

17. Others associatedsymptoms

697

18. Burning sensation inabdomen

Nausea

Diarrhoea

Skin rashes

19. TC (Cells/Cmm.)

20. DCLLLL P _____% P _____% P _____%L _____% L _____% L _____%E _____% E _____% E _____%M_____% M_____% M_____%B _____% B _____% B _____%

21. ESR (mm / 1st hour.)

22. Peripheral smear ofblood

23. M.C.H.C. (%)

698

7. MENSTRUAL DIARY

MENSTRUAL DIARY FOLLOW UP

Initial (Zero) First month Second month Third month

Date of on set ofmenstruation

Menstruation

(i) length of menstrualcycle in days

(ii) Duration of menstrualflow in days

(iii) Amount of bleedingper day (in pads)

Abdominal pain

(i) Day of onset

(ii) Intensity

(iii) Day of relief of pain

Nature of pain

(i) Toda

(ii) Bheda

(iii) Sula

Associated symptoms

(i) Pain in lower limbs

(ii) Nausea / Vomiting

(iii) Constipation

(iv) Giddiness

(v) Breast tenderness

(vi) Diarrhoea

(vii) Headache

(viii) Fainting

699

Adverse Reactions

(i) Burning sensation inabdomen

(ii) Nausea

(iii) Diarrhoea

(iv) Skin rashes






Continuing (1)

Drop out (2) Reason: _____________________________

Died (3) Cause: _______________________________


700

Blank

CARDIOVASCULAR SYSTEM

SEC

TIO

N - X

I

702

Blank

703

Drug: Study Code:


RANDOMIZED DOUBLE BLIND CONTROLLEDCLINICAL TRIAL OF AYUSH-HT IN ESSENTIAL

HYPERTENSION


704

Blank

705

I. BACKGROUND

Hypertension is the largest risk factor for cardio-vascular disease. This condition may becomparable with Raktachapa or Vyanabala Vaishamya1 in Ayurveda. This risk is unevenlydistributed because it is also dependent on the number and extent of concomitant risk factors.

Definition: Criteria for the diagnosis of hypertension in various age groups as defined by7th Joint National Committee Report is as follows:

Hypertension is defined as a sustained increase in systolic BP (SBP) of 140 mm Hg orgreater and/or diastolic BP (DBP) of 90 mm Hg or greater. By the usual criteria of average threeB.P. measurements on one occasion 140 systolic and/or 90 mm Hg Diastolic or taking ofhypertensive medication.

Classification of Blood Pressure (Joint National Committee – 7 (JNC-7) guidelines2


RANDOMIZED DOUBLE BLIND CONTROLLED CLINICAL TRIAL OFAYUSH-HT IN ESSENTIAL HYPERTENSION

References

1. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation andTreatment of High Blood Pressure. JAMA 2003; 289(19): 2560-2572.

2. Gordon H. Williams Hypertension vascular disease page 1414-29, Harrison’s Principle of InternalMedicine, Vol.-I, 15th Edition.

3. Dwiwedi S. Aggarwal MP: Antianginal & Cardioprotective effects of T. Arjuna: An indigenousdrug in coronary Artery disease. J. Ass. Phys. India 1994: 42: 287-289.

4. P.K. Gupta & R.H. Singh: A study on the effect of vaca in cases of essential hypertension andIHD J.R.A.S. Vol.XVI No.3-4 (1995) PP 93-101.

5. P.V. Sharma Dravya Guna Vigyan 2nd part. Page 31-32.

Category Blood Pressure mm Hg.

Systolic Diastolic

Normal < 120 and < 80

Prehypertension 120-139 or 80-89

Stage 1 hypertension 140-159 or 90-99

Stage 2 hypertension > 160 or > 100

706

In more than 95% of cases, aetiology of hypertension is unknown. Such patient isdiagnosed as essential hypertension. Secondary hypertension results as a consequence of aspecific disease or abnormality e.g. renal disease, endocrine disorder, drugs, pregnancy.

There are various modern drugs available as anti-hypertensive e.g. Betablockers, ACEinhibitors, Calcium channel blockers and diuretics but these drugs have side effects and most ofthese are not cost effective. Hence, the search for potent safe and cost effective Ayurvedic anti-hypertensive drugs is exxential.

Ayurvedic drugs like Arjuna, Vacha, Punarnava & Sarpagandha possess anti hypertensiveand cardioprotective effect.

II. OBJECTIVE

To study the effect of Ayurvedic drugs Ayush-HT in essential hypertension.

III. CENTRES

Identify Center of CCRAS


Trial drug : 50 cases

Control : 50 cases

Total Sample Size : 100 at each centre

Level of study : OPD


1. Trial drug: Ayush-HT draggee 750 mg. (Extract of equal parts of Arjuna +Punarnava + Vacha + Sarpagandha)

Dose: One draggee BD with water after meal.

Duration – Six months (6 months follow up with drug in cases showing control inHypertension after 6 months of treatment)

2. Control drug: Hydrochlorothiazide 25 mg. OD with water after the breakfast forsix months. (Control drug will be made similar to trial drug and one placebodraggee will be prescribed after dinner)

All patients included into the study will be advised to take prescribed diet regimen & lightexercise as per given along with patients information sheet.

Design of the study – Randomized Double Blind Control Clinical trail

707

Duration of the study – six months (6 months follow up with drug in cases showingcontrol in Hypertension after 6 months of treatment).

Total duration: will be three years to complete the trial.


1. Diagnosed patients of essential hypertension of duration < one year without taking anyanti-hypertensive medication for at least one month

S.B.P. < 160 mm. Hg. and >= 140 mm Hg.

D.B.P. < 100 mm. Hg. and >= 90 mm. Hg.



1. Patient below 35 years and above 60 years of age.

2. Patients with

S.B.P. >= 160 mm. Hg.,<140 mm Hg

D.B.P. >= 100 mm. Hg. and < 90 mm. Hg

3. Patient receiving on anti hypertensive drug

4. Complicated hypertensive cases e.g. Nephropathy and left ventricular hypertrophy, heartblock, congestive heart failure, coronary artery disease and retinopathy

5. Patients suffering with Diabetes

6. Accelerated and malignant hypertension.

7. Patient taking steroids oral contraceptive pills, oestrogen replacement therapy or NSAIDgroups of drug.

8. Pregnant women or planning pregnancy with in six months.

9. Patient with severe other illness hepatic/renal failure.

10. Secondary hypertension.


During the course of the trial treatment, if any serious condition develops/symptomsaggravates due to increase in S.B.P. and D.B.P. which requires urgent treatment , such subjectsmay be withdrawn from the trial and managed by the Principal Investigator accordingly.

708


The full details of history and physical examination of the patients will be recorded as per theproforma (Forms I & II). Clinical assessment will be done fortnightly during the treatment period andfollow up period (Form III). The laboratory investigations will be recorded before treatment period,at the end of three months, end of the treatment period and end of the follow up.

IX. ASSESSMENT OF RESULTS

Adequate Blood pressure control i.e. D.B.P. below 90 mm Hg. and S.B.P. below 140mm. Hg. on three successive readings will be considered as significant outcome of the treatment.


Data on clinical symptoms, physiological parameters and laboratory parameters will betabulated & analyzed using appropriate statistical methods.


The monitoring of progress of the trial and data analysis will be undertaken by CCRASHQrs., New Delhi.

XII. ETHICAL REVIEW

Each Institutional Ethical Committee (IEC) of participating Centre’s should give clearancecertificate before the project is initiated. Patient’s information sheet and informed consent formshould be submitted alongwith project proposal for approval by IEC. Both should be maintainedin duplicate with


A consolidated amount of Rs. ——————— per visit will be paid to subject onevery visit.





709






Name: ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “Randomized double blind controlled clinical trial of ayush-HT inessential hypertension”.





Relationship ___________________________________


710





The available treatment for essential hypertension in modern medical science likeBetablockers, ACE inhibitors, Calcium channel blockers, a blockers and diuretics but these drugshave side effects and most of these are not cost effective. Hence the search for potent safe andcost effective Ayurvedic anti-hypertensive drugs.


Your doctor will explain clearly what you have to do. It is important that you shouldfollow the instructions scrupulously. The study will take approximately one year to complete (sixmonths treatment period and six months follow up). During this period, you are expected to visitthe hospital 24 times, fortnightly during treatment phase and follow up period.

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination, ECG an X-ray and Findus examination. Blood and urine samples will also betaken. This is to make sure that you are eligible for the study.

If you are found eligible, you would be put on dietary regimen prescribed in theinformation sheets besides light exercise. This should be followed during treatment period. Duringtreatment you will receive either the trial drug or control drug. In cases showing control inhypertension trial drug will be continued for another six months. After end of the study, patientwill be advised to continue treatment as per advice of the physician.

At each visit, you will be supplied with sufficient quantities of drugs to last until your nextvisit.

Diet regimen: The patients are advised to restrict salt intake (ie less than 5gm per day)and follow diet as per advice of the treating physician.

Advice for Exercise: The patients are advised to do brisk walking/Jogging or lightexercises for about 30 minutes per day.

The patients will also be advised to avoid smoking.


711




(Before Treatment)


1. Centre : ...................................


3. Subject Name : ....................................................................................................................


5. Address : ............................................................................................................................................................................................................................................................


1. Diagnosed patients of essential hypertension of duration < one year without taking any anti-hypertensivemedication for 1 month S.B.P. < 160 mm. Hg. > =140 mm Hg.and D.B.P. < 100 mm. Hg. and >= 90 mm. Hg.



3. Patient below 35 years and above 60 years of age.

4. Patients with

S.B.P. > =160 mm. Hg.,<140 mm Hg and

D.B.P. > =100 mm. Hg. and < 90 mm. Hg

5. Patient receiving conventional anti-hypertensive drug regularly

6. Complicated hypertensive cases e.g. Nephropathy and left ventricular hypertrophy, heart block, congestive heart failure,coronary artery disease and retinopathy

712

7. Patients suffering with Diabetes mellitus

8. Accelerated and malignant hypertension.


10. Pregnant women or planning pregnancy with in six months

11. Patients on steroids oral contraceptive pills, oestrogen replacement therapy or NSAID groups of drug.

12. Patient with severe other illness hepatic/renal failure.



If Sl. No. 1 to 2 is ‘Yes’ and Sl. No. 3 to 13 are ‘No’.

If admitted, Sr. No. of the Subject: ________________________________________________

Date: ____________ Signature of the Investigator _________________

713




1. Centre : ...................................


3. Subject Name : ....................................................................................................................


5. Address : ..............................................................................................................................










Indicate nature of work : .........................................................................

10. Income per capita per month in Rs. .....................................................................................

Chief complaint with duration (if any) in days Yes (1) No (0) Duration(in days)

11. Giddiness

12. Irritability

714

13. Fatigue

14. Lack of sleep

15. Headache

16. Any chest pain/palpitation

17. Breathlessness with or without exertion

18. Other symptoms if any specify______________________________________________

History of Present illness:

19. Duration of disease in months_______________________________________________

Treatment received so far Yes (1) No (0)

20. Beta Blockers

21. Calcium Channel Blockers

22. Diuretics

23. Others

24. If yes, specify ___________________________________________________________

Personal History:

25. Diet: Veg Non-veg

26. Sleep: Normal Distrubed

Yes (1) No (0)

27. Presence of Emotional Stress

28. Constipation

29. Occupation: Sedentary Moderate Work

Hard Work

715

Addiction Yes (1) No (0)

30. Smoking

If yes specify: (a) Quantity (Packs) : _____________________

(b) Total Duration in years : ________________

31. Tobacco

If yes specify: (a) Quantity ____________________________

(b) Total Duration in years : _______________

32. Alcohol

If yes specify : (a) Quantity ___________________________

(b) Total Duration in years : _______________

33. Any other (specify) _______________________________________________________



Sannipataj

Family History: Present (1) Absent (0)

32. Hypertension:

Parent:

Siblings:

33. Hypercholesterolemia

Parent :

Siblings:

34. PHYSICAL EXAMINATION:

a) Built Lean Medium Heavy

716

b) Gait Normal Abnormal

c) Body weight ____________ Kg.

d) Body temperature ____________oF

e) Blood pressure: ____________

Systolic ____________ mm/Hg (in sitting posture of right upper limb)

Diastolic ____________ mm/Hg

f) Pulse rate: ____________ /min. (Radial pulse of right upper limb)

g) Respiration rate: ____________ /min.


h) Pallor

i) Jaundice

j) Koilonychia

k) Lymphadenopathy

l) Edema

35. SYSTEMIC EXAMINATION Normal Abnormal

a) CVS with chest

If Abnormal, specify abnormalities____________________________________________

b) CNS


c) Digestive system


d) Uro-genital system


717

e) Respiratory system


f) Abdomen Palpable Not palpable

i) Liver

ii) Spleen

g) Eye examination

If abnormal details of vision disturbance and Fundoscopy _________________________

Date: _____________ Signature of Investigator ___________________

718



CASE RECORD FORM III -PERIODICAL OBSERVATION AND ASSESSMENT

(Fortnightly during treatment period and follow up)

1. Centre : ...................................


3. Subject Name : ....................................................................................................................


5. Address : ..............................................................................................................................



Clinical Parameters

a. Subjective Present (1) Absent (0)

8. Giddiness

9. Irritability

10. Fatigue

11. Lack of sleep

12. Headache

13. Any chest pain/palpitation

14. Breathlessness with or without exertion

15. Other Complaints with if any specify_________________________________________

719

b. Objective

15. Weights ________________________Kg

16. Resting Systolic B.P _________________________mmHg

17. Resting Diastolic B.P _________________________mmHg

Date: _____________ Signature of the Investigator: ________________

720





(Before treatment, end of the 3rd month and after the treatment)

1. Centre : ...................................


3. Subject Name : ....................................................................................................................


5. Address : ..............................................................................................................................



Urine Examination

Routine

8. Sugar: __________________

9. Albumin __________________

10. Deposits __________________

Microscopic

11. Pus cell __________________(hpf)

12. RBC __________________(hpf)

13. Cast __________________(hpf)

721

Stool examination

14. Routine __________________

Microscopic

15. Ova __________________

16. Cyst __________________

17. Occult Blood __________________

Blood

18. Blood Group __________________

19. TC(Cells/Cmm.) __________________

20. DLC: P(%)________ L(%)________ E(%)________M(%)________B(%)________

21. Hb (g/dl) __________________

22. ESR (1st hour.) __________________

23. Blood Sugar- Fasting(mg./dl) __________________

24. Blood Sugar – PP (mg./dl) __________________

25. Blood Urea (mg./dl) __________________

26. S. Creatinine (mg./dl) __________________

27. Uric acid (mg./dl) __________________

LIPID PROFILE

28. Serum total Cholesterol (mg./dl) __________________

29. S. Triglycerides (mg./dl) __________________

30. HDL(mg./dl) __________________

31. LDL(mg./dl) __________________

32. VLDL(mg/dl) __________________

722

LIVER FUNCTION TEST

Serum Bilirubin

33. Total (mg/dl) __________________

34. Direct (mg/dl) __________________

35. SGOT (IU/L) __________________

36. SGPT (IU/L) __________________

37. Alk.Phosphatase (KA units) __________________

38. Total proteins (gm./dl) __________________

39. Albumin (gm./dl) __________________

40. Globulin (gm./dl) __________________

41. A/G Ratio __________________

Serum Electrolytes

42. Sodium (mEq/L) __________________

43. Potasium (mEq/L) __________________

Other investigations

44. ECG __________________

45. X-ray chest (PA View) (only at the beginning of study) _____________________________

46. Fundoscopy (only at the beginning of study) ______________________________________

Date: _____________ Signature of the Investigator: _________________

723

Diet Regimen:

To take 25 kCal/kg per day (Moderate work)

Protein 0.8 gm/kg per day

Fat < 30% of calorie (Saturated fat < 10% Polyunsaturated fat < 8% of total diet)

Cholesterol < 300 mg per day

Dietary fibre 50 gm per day (atleast)

Common salt < 5 gm. per day

Saturated fat e.g. Ghee, Vanaspati, Dalda, Palm, Coconut oil, egg and meet These contain highlysaturated fat and cholesterol.

Sun flower oil, Soyabean oil, Olive oil contain unsaturated fat it should be taken 3 small teaspoonful per day.

Milk: Three cup daily double tone

Whole Cereal: 90 gm daily. Example old Sama rice, wheat, java, with husk.

Vegetable: 250 gm daily. Example Pumpkin, methi, padwal, karaila, and beans.

Non polished Dal: 75 gm. Daily. Example Moong, Masoor, Chana, Arhar.

Fruits: 250 gm. Daily.Example all seasonal like mango, apple, cucumber, pear dhatriphal,

Spices: 05 gm. Per day coriander, Ginger, and Cardamom.

724

Blank

725

Drug: Study Code:


PROTOCOL FOR PLACEBO CONTROLLED MULTI-CENTRIC CLINICAL TRIAL OF AN AYURVEDIC

FORMULATION IN THE MANAGEMENT OFCHRONIC STABLE ANGINA


726

Blank

727

I. BACKGROUND

Coronary artery disease is an important cause of morbidity and mortality. The incidenceand prevalence of the disease is gradually rising in our country and a substantial portion of adultpopulation is affected. Some of the Ayurvedic drugs investigated so far have shown encouragingcardio-protective potential. The classical literature in Ayurveda has described the usefulness ofArjuna1 and Pushkarmula2 in prevention and treatment of Hridroga (cardiac angina speciallyrelating to Ischaemic heart diseases). The studies on Arjuna3,4,5 and Pushkarmula,6,7,8,9,10 in manycenters have put forth the efficacy of the drug in the management of ischaemic heart disease andhas been practiced in preventive cardiology. They lower lipids in patients and prevent the increasein lipids in experimental animals.

Keeping in view the references with the ancient classical literature of Ayurveda and theleads obtained in the recent studies, the combination of Arjuna and Pushkarmula has beenselected for trial in prevention of cardiac risk factors in cases of Chronic Stable Angina.


PLACEBO CONTROLLED MULTI-CENTRIC CLINICAL TRIAL OF ANAYURVEDIC FORMULATION IN THE MANAGEMENT OF CHRONIC

STABLE ANGINA

References

1. Chakrapani; Chakradutta; Chaukhamba Publication, Varanasi; 3rd Edition, Hridroga (Chapter 21),verses 8 & 9

2. Charaka Samhita; Chaukhamba Publication, Varanasi; 2nd Edition; Sutra Sthana, Chapter 25,Verses 40 and Chikitsa sthana, Chapter-26, verses 84-86.

3. Colabawalla, H.M., An Evaluation of Cardio-tonic and other properties of Terminalia arjuna,Indian Heart.J.3;205-30, 195

4. Singh, N.et.al.: Mechanism of Cardiovascular response of Terminalia arjuna, Ind.J.Pharmacol. II(I) : 33, 1979

5. Ojha J.K. et.al., I.racemosa, as Hypolipidaemia agent (an experimental and clinical study), IndianJ.Pharm.39 (6);176, 1977

6. Singh, Ramji, et.al. Pushkara guggulu - an Antianginal and Hypolipidaemic Agent in CoronaryHeart Disease (CHD), JRAS, Vol.XII, No.1-2, Pp-1-18 (1990)

7. Singh, N.et.al.; Pharmacological studies on I.racemosa, J.Res. Indian Med.Yoga and Homoeo11(3):25-32, 1976.

8. Dwivedi S, Agarwal MP. Antianginal and cardioprotective effects of Terminalia arjuna: Anindigenous drug in coronary artery disease.J Ass Phys India 1994; 42:287-289.

9. Bharani A, Ganguli A, Bhargava KD. Salutary effect of Terminalia arjuna in patients with severerefractory heart failure. Int. Journal Cardiol 1995;49:191-99.

10. Dwivedi S, R. Jouhari.Beneficial effects of Terminalia arjuna in Coronary artery disease: IndianHeart J.; 49:507-10.

728

II. OBJECTIVE

Effect of Arjuna barks powder and aqueous extracts of Pushkarmula on Chronic StableAngina.

III. CENTRES




Run-in Period : One week

Groups : Two (Trial and Control)


Group-I Trial drug

a). Drug : Arjuna twaka (bark of Terminalia arjuna W. & A.) andPushkarmula (root of Inula racemosa Hook. f.) incapsule form (each capsule containing Arjuna barkpowder 500 mg. and aqueous extract of Pushkarmuladerived from 500 mg. of crude drug).

b). Dosage : Three capsule of 500 mg each twice a day.

c). Duration : 90 days

Group II- Control drug (Control drug will be made similar to trial drug)

Design of the study : Randomized Double–blind Placebo controlled study.

Duration of : One week run-in period and three months drug therapythe study with follow up for three months without drug.

Period of Study : Period of study will be six months for each case. Totalduration will be two and half years to complete the trial ateach Centre.


1. Age more than 35 years of either sex

2. Diagnosed cases of Chronic Stable Angina.

3. TMT positive cases

729


1. Age below 35 years

2. Recent M.I. less than three months

3. Patients with conduction problem

4. Patients with uncontrolled hypertension

5. Unstable Angina

6. Serious concomitant disease of liver and/or kidney

7. Any malignancy

8. Undergoing treatment for any other serious illness


If during the course of the trial treatment, subjects shows the following:

1. any serious toxicity for intolerance,

2. acute myocardial infarction,

3. stable angina progressing to unstable angina and/or,

4. undergoing Coronary re-vascularisation

Subject will be withdrawn from the study. If any other serious condition develops duringthe course of study, which requires urgent treatment, such subjects will also be withdrawn from thetrial and managed by the Principal Investigator accordingly.


The full details of history and physical examination of the patients will be recorded as perthe Performa (Forms I & II). Clinical assessment will be done before drug administration (0),after one week of Run-in period, every six weeks during treatment and at the end of follow up(Form III) (after three months of completion of treatment). The laboratory investigations and TMTwill be recorded before drug administration, after one week of Run-in period and after completionof treatment (Form-IV). All the patients will be provided a ‘Diary of Events’ for keeping recordof angina attacks and consumption of nitrate tablets.


Data on frequency of angina, consumption of nitro-glycerin tablets, duration of exercisetolerance on TMT (end point), time taken for 1 mm ST depression, maximum double product,lipid profile at the end of run-in period and at the end of treatment will be analyzed usingappropriate statistical methods.

730


The assessment of progress & outcome of treatment are assessed on the basis ofimprovement in the symptoms.


The progress of the trial will be monitored by Monitoring Unit of CCRAS Head Quarters,New Delhi.

XII. ETHICAL REVIEW

Each participating center’s Institutional Ethical Committee (IEC) should give a clearancecertificate before the project is initiated. Patient’s information sheet and informed consent formshould be submitted along with the project proposal for approval by IEC. Both should bemaintained in duplicate with one copy given to the patient at the time of entry to the trial.


A consolidated amount of Rs…../- per visit will be paid to subject selected for trial.


Short-term two-day training will be provided to the Investigators and Laboratorypersonnel involved in the multi-centric trial at CCRAS Hqrs. New Delhi. The investigators andtechnicians will be detailed about the clinical trial conduct and laboratory procedures in order tomaintain the uniformity.


The Laboratory Investigations (Pathological/Biochemical, etc.), which are not available atresearch Institutes should be conducted at identified reputed labs /Government Institutes underintimation to this Council about codal formalities.

731



STABLE ANGINA





Name: ____________________________

CONSENT BY SUBJECT

I have been informed to my satisfaction, by the attending doctor, the purpose of theclinical trial and the nature of drug treatment and follow-up, including the laboratory investigationsto be performed to monitor and safeguard my body functions.


I, exercising my free power of choice, hereby give my consent to be included as a subjectin the “Clinical trial of Arjuna and Pushkarmula in the cases of Chronic Stable Angina”.





Relationship ___________________________________


732



STABLE ANGINA



Ayurveda has a very comprehensive approach for the treatment of chronic stable angina.The present study is aim to evaluate selected Ayurvedic drugs for their efficacy in the treatment ofIschemic heart disease. You are invited to participate in this study where you will be provided acombination of Arjuna and Pushkarmula in daily dose of three capsules BD. The previousobservations in clinical and experimental studies have shown promising effect of these drugs in thetreatment of Ischemic heart disease. About 300 cases of Ischemic heart disease from thisand other hospitals around the country will be taking part in this study.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately six months to complete (three monthsfor treatment and another three months for follow-up study). During this period, you are expectedto visit the hospital five times (0, after one week, six week, 12 week and six months).

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination, ECG, X-ray, TMT. Blood and urine samples will also be taken. This is tomake sure that you are eligible for the study. Clinical assessment and lab investigations will becarried out during subsequent visits.

If you are found eligible, you would be put on trial treatment for three monthsand on follow up for three months. The daily dosage will be three capsules twice a day.At each visit, you will be supplied with sufficient quantities of drugs to last until yournext visit.


733



STABLE ANGINA


BEFORE TREATMENT


1. Centre : ...................................


3. Subject Name : ....................................................................................................................



6. Address : ............................................................................................................................................................................................................................................................



2. Diagnosed cases of chronic stable angina

3. TMT positive case



5. Recent M.I. less than three months

6. Patients with conduction problem

7. Uncontrolled hypertension

8. Unstable Angina

734

9. Serious concomitant disease of liver / kidney

10. Malignancy

11. Patients undergoing treatment for any other serious illness



If admitted, subject serial No.: ___________________



735



STABLE ANGINA



1. Centre : ...................................


3. Subject Name : ....................................................................................................................


5. Address : ..............................................................................................................................



Chief complaint with duration (if any) in days Present (1) Absent (0) Duration

8. Chest pain [NYHA Criteria]

If present, indicate:

Location________________________________________________________________

Radiation________________________________________________________________

Type of pain_____________________________________________________________

Frequency of anginal attacks per week ___________________________________________

9. Post-prandial pain

10. Dyspnoea on exertion

11. History of CAD if any in the Past

736

History of present illness

12. Duration of disease (in months)______________________________________________

Treatment given so far Yes (1) No (0)

13. Beta blockers

14. Calcium channel blocker

15. Nitrates

16. Others

If yes, specify____________________________________________________________

17. Family History of CAD

If yes, specify____________________________________________________________

PERSONAL HISTORY

18. Smoking/Tobacco/Pan masala

19. Constipation

20. Sharirik Prakriti: Vataja 1 Pittaja 2 Kaphaja 3

Vata-kaphaja 4 Vatapittaja 5 Pitta-kaphaja 6

Sannipataja 7


General

21. Body weight (Kg.) ________________________

22. Body height (in cm) ________________________

23. Resting Blood pressure (Systolic) mm of Hg ________________________

24. Resting Blood pressure (Diastolic) mm of Hg ________________________

737


Cardiovascular

25. Pulse Rate (per minute) ____________________________________________________

26. Pulse Rhythm Regular 0 Irregular 1

27. Apex beat Normal 0 Abnormal 1

28. Heart sound Normal 0 Abnormal 1


29. Jugular venous pulse. Normal 0 Abnormal 1


30. Congestive Cardiac Failure

31. Oedema

GASTRO INTESTINAL TRACT

32. Hepatomegaly

33. Splenomegaly

RESPIRATORY

34. Crepitation

35. Rhonchi/Wheezing

CENTRAL NERVOUS SYSTEM

36. Normal Yes 1 No 0


738



STABLE ANGINA


(0, 1st, 7th, 13th and 25th week)

1. Centre : ...................................


3. Subject Name : ....................................................................................................................





Clinical Parameters

A. Subjective Present (1) Absent (0)

8. Chest pain

[NYHA Criteria for Class II/III]

If present, indicate:

Location _____________

Radiation _____________

Type of pain _____________

Frequency of anginal attacks per week

12. Post-prandial pain

739

13. Dyspnoea on exertion

B. Objective

11. Body weight (in kg): ______________________________________________________

12. Resting Blood pressure (Systolic) (mm of Hg): __________________________________

13. Resting Blood pressure (Diastolic) (mm of Hg): _________________________________


740


1 2 3 4

Adverse

Experience


PLACEBO CONTROLLED MULTI- CENTRIC CLINICAL TRIAL OF ANAYURVEDIC FORMULATION IN THE MANAGEMENT OF CHRONIC

STABLE ANGINA


(0, 15, 30, 45, 60, 75, 90 days)

1. Centre : ...................................


3. Subject Name : ....................................................................................................................




7. Address : Permanent postal address with phone number and email if any.

..............................................................................................................................

..............................................................................................................................

ADVERSE EVENTS


741

Date started

Date

Time

Date stopped

Pattern

Isolated-1

Intermittent-2

Continuous-3

Severity

Mild-1

Moderate-2

Severe-3



Serious*

Yes-1

No-2





742

Relationship

to study

medication

Unrelated-1

Possible-2

Probable-3










743



STABLE ANGINA

CASE REPORT FORM IV – LABORATORY INVESTIGATIONS('O' day, after one week of Run in period and after end of the treatment)

1. Centre : ...................................


3. Subject Name : ....................................................................................................................




7. Address : Permanent postal address with phone number and email if any.

..............................................................................................................................

..............................................................................................................................


9. Stage of Assessment (in weeks)

Urine Examination (Microscopic)

10. Sugar: ______________

11. Albumin: ______________

12. Deposits: ______________

Blood

13. Hb(g/dl): ______________

14. Blood Sugar-Fasting (%) ______________

15. Blood Sugar – PP(mg./dl)______________

16. S. Cholesterol (mg./dl) ______________

744

17. HDL (mg./dl) ______________

18. LDL (mg./dl) ______________

19. Triglycerides (mg./dl) ______________

20. B. Urea (mg./dl) ______________

21. S. Creatinine (mg./dl) ______________

22. Uric acid (mg./dl) ______________

23. SGOT ______________

24. SGPT ______________

Radiological Investigations

25. X-ray Chest: [ 0 Month only ] ___________________________________

___________________________________

Special Tests

26. ECG (report all details) ___________________________________

___________________________________

TMT (Bruce Protocol)

27. Duration of exercise (in minutes & seconds) (min.) (sec.)

{Mets-…….]

28. Time to 1mm ST depression( in seconds)

29. Maximum double product

30. Maximum ST segment depression (in mm)

31. Leads showing ST depression:

L1

L2

L3

aVR aVL aVF

V1

V2

V3

V4 V

5 V

6

If in other special leads, specify________________________________________

Date: _____________ Signature of the Investigator ______________________

URINARY SYSTEM

SEC

TIO

N - X

II

746

Blank

747

Drug: Study Code:


MULTICENTRIC DOUBLE BLIND PLACEBOCONTROLLED CLINICAL TRIAL OF AN AYURVEDIC

FORMULATION ON MUTRASHMARI(UROLITHIASIS)


748

Blank

749

I. BACKGROUND

Urinary calculi consist of aggregation of crystals and small amounts of proteins andglycoproteins but their genesis is poorly understood. Different types of stone occur in differentparts of the world with different chemical composition. Dietary factors probably play a part indetermining the varying patterns. In developing countries, bladder stones are common particularlyin children. In industrial countries the incidence of childhood bladder stone is low and renal stonesin adults are more common. In this condition there may be urinary calculi anywhere in the urinarytract.

Detailed descriptions concerning the etiology, clinical features and line of management ofthis condition is available in classical literature of Ayurveda. The common features of presentationare pain and obstruction to flow of urine with/without haematuria. The management of urinarycalculi is revolutionized during the last 2-3 decades. The surgical treatment, endourology andESWL can effectively treat/manage the existing calculi but the problem of residual fragments andrecurrence of calculi persists.

The medical treatment is effective in the management of small calculi, residual fragmentsand prevention of urinary calculi. Keeping this in view various Ayurvedic drugs like Shveta Parpati,Gokshuru, Varuna, Pashana Bheda, Kulattha and Palash Kshara prescribed in ancient Ayurvedictexts have been studied in the management of this condition.


MULTICENTRIC DOUBLE BLIND PLACEBO CONTROLLED CLINICALTRIAL OF AN AYURVEDIC FORMULATION ON MUTRASHMARI

(UROLITHIASIS)

References

1. Sannd, B.N., Kumar, Anil and Kumar, Naresh: To evaluate the effect of Ayurvedic DrugsShveta Parpati with Pasana Bheda and Gokshuru in the management of Mutrashmari(urolithiasis); JRAS, Vol.XIV, No. 3-4 , Pp.98-114, 1998.

2. Kumar, Anil and Kumar, Naresh: To evaluate the effect of Ayurvedic drugs – a herbomineralcomibiation of Shveta Parpati with Kulatha Kwatha in the management of Mutrashmari(urolithiasis); JRAS, Vol. XVI, No.1-2, Pp.35-42, 1995.

3. Kumar, Anil and Kumar, Naresh: To evaluate the effect of Palasha Kshara in the managementof Mutrashmari (Urolithiasis); JRAS, Vol.XVI, No.1-2, Pp.43-50, 1995.

4. Singh, L.M., Shukla, J.P. and Deshpande, P.J.: Monograph on “Management of Mutrashmariby three Ayurvedic Drugs Varuna, Kulatha and Gokshuru”, C.C.R.A.S., New Delhi, 1987.

750

Shveta Parpati with decoction of Gokshuru and ,Pashana Bhed1; Shveta Parpati withdecoction of Kulattha2; Palash Kshara3; and Varuna, Kulattha and Guggulu4 have been found quiteeffective in management this condition. The present multricentric clinical trial is proposed with aview to re-establish the efficacy of this formulation for the management of urolithiasis.

II. OBJECTIVE

To assess the efficacy of Shveta Parpati and Palash Kshara with the aqueous extract ofKulattha, Pashana Bheda, Gokshuru in the cases of Mutrashmari (Urolithiasis).

III. CENTRES

CCRAS centers in collaboration with other centers.


Sample Size : 120 Subjects (60 subjects in each group)

Groups : Two – trial and control

Drug/Dosage/Duration : Trial drug in one group

(i) Drug : Shveta Parpati1and Palash Kshara2 with theaqueous extract of Kulattha3, Pashan Bheda4 andGokshuru5, all in equal quantity.

(ii) Dosage : Two capsules of 500 mg each TDS

(iii) Duration : 90 days and placebo in another group.

Design of the study : Randomised Double – blind Placebo controlledstudy.

Duration of the study : Three months drug therapy with follow up for ninemonths without drug

Total period of study : Total one year, registration of the patients shouldbe done only in first fifteen months of the start ofthe study.

Period of Study : Twelve months for each case. Total duration will betwo and half years to complete the trial at eachCentre.

Follow – Up : Three follow-ups will be carried out after 3rd, 6th

and 9th after completion of treatment.

751


1. Age: between 15 to 60 years

2. Sex: either sex

3. Radiological evidence of stone (upto 10 mm) in kidney, ureter and urinary bladder



2 Stone size more than 10 mm

2. Impacted stone

3. Gross hydronephrosis

4. Pyelonephritis


6. Malignancy

7. Impaired renal function

8. Poorly functioning kidney

9. Patients with obstruction in urinary passage.

10. Patients with known metabolic abnormality for calculus formation

11. Any other complication of calculus.



During the course of the trial treatment, if any serious condition develops which requiresurgent treatment such subjects may be withdrawn from the trial and managed by the PrincipalInvestigator accordingly.


The full details of history and physical examination of the patients will be recorded as perthe proforma (Forms I & II). Clinical assessment will be done before drug administration (0), atthe end of Ist, IInd, IIIrd months during treatment and at the end of 6th, 9th and 12th monthsduring follow up (Form III). The laboratory and radiological investigations will be recorded beforedrug administration (0 month), at the end of treatment (3 months) and at the one year (12months) as per proforma (Form IV)

752


Radiological evidence of disappearance or reduction in the size of the stone, Clinicalparameters and laboratory parameters will be analysed using appropriate statistical methods.


The progress of the trial will be monitored by Monitoring Unit of CCRAS Head quarters,New Delhi.

XI. ETHICAL REVIEW

Each participating centre’s Institutional Ethical Committee (IEC) should give clearancecertificate before the project is initiated. Patient’s information sheet and informed consent formshould be submitted alongwith project proposal for approval by IEC. Both should be maintainedin duplicate with one copy given to the patient at the time of entry to the trial.







753



(UROLITHIASIS)

PATIENT CONSENT FORM




Name: ____________________________

CONSENT BY SUBJECT

I have been informed to my satisfaction, by the attending doctor, the purpose of theclinical trial and the nature of drug treatment and follow-up, including the laboratory investigationsto be performed to monitor and safeguard my body functions.


I, exercising my free power of choice, hereby give my consent to be included as a subjectin the “Clinical trial of Shveta Parpati, Palash Kshara, Kulattha, Pashana Bheda and Goksuru inthe cases of Mutrashmari (urolithiasis)”.





Relationship ___________________________________


754



(UROLITHIASIS)



Ayurveda has a very comprehensive approach for the management/treatment ofMutrashmari (Urolithiasis). The present study is aim to evaluate selected Ayurvedic drug for itsefficacy in the treatment of Urolithiasis. You are invited to participate in this study where you willbe provided a combination of Shveta parpati, Palash Kshara, Kulattha, Pashana Bheda andGokshuru. in daily dose of two capsules TDS. The previous observations in clinical andexperimental studies have shown promising effect of these drugs in the treatment of Urolithiasis.About 360 cases of urolithiasis from this and other hospitals around the country will be taking partin this study.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 12 months to complete (3 months fortreatment and another 9 months for follow-up study). During this period, you are expected to visitthe hospital seven times (0, 1st, 2nd, 3rd, 6th, 9th and 12th months). The interval between the first,second, third and fourth visits will be around four weeks. Then there will be three more visits afterevery three months of last visit of third month.

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination, ECG, X-ray and IVP. Blood and urine samples will also be taken. This is tomake sure that you are eligible for the study.

If you are found eligible, you would be put on trial treatment for 3 months and onfollow up for 6 months. The daily dosage will be two capsules thrice a day. At each visit,you will be supplied with sufficient quantities of drugs to last until your next visit.


755



(UROLITHIASIS)


BEFORE TREATMENT


1. Centre : ...................................


3. Subject Name : ....................................................................................................................



6. Address : ............................................................................................................................................................................................................................................................



2. Either Sex

3. Radiological evidence of stone upto 10 mm in size



5. Stone size more than 10 mm

6. Gross hydronephrosis

7. Pyelonephritis


756

9. Malignancy

10. Impacted stone

11. Impaired Renal Function

12. Poorly functioning kidney

13. Patients with obstruction in urinary passage.

14. Patients with known abnormality of calculus formation

15. Any other complication of calculus.




If admitted, subject serial No.: ___________________



757



(UROLITHIASIS)



1. Centre : ...................................


3. Subject Name : ....................................................................................................................





Illiterate (1) 1 Read and write (2) 2 Primary (3) 3

Middle school (4) 4 High school (5) 5 College (6) 6

Others (specify) (7) 7 INA (8) 8

10. Occupation




Indicate nature of work………………………….................................................

Chief complaints with duration in days Absent (0) Present (1) Duration

9. Intermittent dull or colickly flank pain

10. Haematuria

758


11. Crystalluria

12. Turbid urination

13. Intermittent flow of urine

14. Increased frequency

15. Burning micturation

16. Others

If yes specify____________________________________________________________


18. Duration of disease (in months)______________________________________________

No (0) Yes (1)

19. Past illness of urinary stone

If yes, give details_________________________________________________________

20. History of any other Urological /Nephrological illness


21. Family history of Urolithiasis


PERSONAL HISTORY

22. Diet Veg.(1) Non-veg (2)

23. Fluid intake Less than one ltr.(1) 1-2 ltr. (2)

2-3 ltr. (3) more than 3 ltr. (4)

24. Prakriti: Vataja 1 Pittaja 2 Kaphaja 3

Vata-kaphaja 4 Vatapittaja 5 Pitta-Kaphaja 6

Sannipataja 7

759

25. Addiction No (0) Yes (1)

If yes, Specify____________________________________________________________



27. Body weight (Kg.) ___________________

28. Body height(in cm) ___________________

29. Blood pressure (Systolic) ___________________

30. Blood pressure (Diastolic)___________________

31. Anaemia Absent (0) Present (1)


32. C.V.S. (with Chest)


33. C.N.S.




35. Respiratory System


Uro-Genital system

36. External gelitalia


37. Prostate


760

Palpable (1) Non-palpable (2)

38. Kidney

39. Bladder

40. Any other, positive finding No (0) Yes (1)



761



(UROLITHIASIS)


(0, 1, 2, 3, 6, 9 & 12th months)

1. Centre : ...................................


3. Subject Name : ....................................................................................................................






Clinical Symptoms Present (1) Absent (0)

9. Intermittent dull or colickly flank pain

10. Haemturia

11. Crystalluria

12. Turbid urination

13. Intermittent flow of urine

14. Increased frequency

15. Burning micturition

16. Other if any

If yes, specify____________________________________________________________

Date: ___________ Signature of the Investigator: ________________

762


1 2 3 4

Adverse

Experience


PROTOCOL FOR MULTICENTRIC DOUBLE BLIND PLACEBOCONTROLLED CLINICAL TRIAL OF AN AYURVEDIC FORMULATION ON

MUTRASHMARI (UROLITHIASIS)


(0, 15, 30, 45, 60, 75, 90 days)

1. Centre : ...................................


3. Subject Name : ....................................................................................................................





ADVERSE EVENTS


763

Date started

Date

Time

Date stopped

Pattern

Isolated-1

Intermittent-2

Continuous-3

Severity

Mild-1

Moderate-2

Severe-3



Serious*

Yes-1

No-2





764

Relationship

to study

medication

Unrelated-1

Possible-2

Probable-3




Possible: Follows a reasonable temporal sequence from administration of the drug; follows a



Probable: Follows a reasonable temporal sequence from administration of the drug; follows a



765



(UROLITHIASIS)


(0, 1st, 3rd and 12th MONTH)

1. Centre : ...................................


3. Subject Name : ....................................................................................................................






Urine Examination

9. Routine: _______________________________

10. pH _______________________________

11. Microscopic _______________________________

12. RBC _______________________________

13. WBC _______________________________

14. CRYSTALCASTS_______________________________

15. Urine culture _______________________________

16. Culture sensitivity_______________________________

766

Hours Urine Analysis

17. Calcium _______________________________

18. Phosphate _______________________________

19. Uric acid _______________________________

20. Total protein _______________________________

21. Oxalate (Optional) _______________________________

22. Citrate (Optional) _______________________________

Blood

23. Hb (g/dl): _______________________________

24. ESR (1st hour.)(mm) _______________________________

25. Parathormone assay(optional) _______________________________

26. Blood Sugar – PP(mg./dl) _______________________________

27. S. Cholesterol(mg./dl): _______________________________

28. B. Urea (mg./dl): _______________________________

29. S. Creatinine (mg./dl) _______________________________

30. Uric acid (mg./dl) _______________________________

31. Total proteins (gm./dl) _______________________________

32. Albumin(gm./dl) _______________________________

33. Globulin(gm./dl) _______________________________

34. A/G Ratio _______________________________

35. Serum calcium (mg/dl) _______________________________

36. Serum phosphate (mg/dl) _______________________________

37. ECG: _______________________________

767

Radiological Investigations

38. X-ray Chest: [ 0 Month only ] _______________________________

Plain X-ray (KUB)* [0, 3rd, 6th, 9th 12th Month] ____________________

39. Radio-opaque shadow

40. Site _______________________________

41. Size (in mm) _______________________________

42. Shape _______________________________

43. Opacity _______________________________

Intravenous pyelography (0, 3 Months)

Kidney

44. Size

45. PCS Normal 1 Abnormal 2

If, abnormal specify _______________________________________________________

46. Hydronephrosis Normal 1 Abnormal 2

If, present indicate grade (I,II,III)_____________________________________________

47. Location of Calculus

48. Ureter Normal 1 Dilated 2

49. Bladder Normal 1 Abnormal 2

Ultra Sound (Optional)

Kidney

50. Size

51. Hyderonephrosis

52. Thickness of parenchyma

768

53. Ureter Normal 1 Dilated 2

54. Bladder Normal 1 Abnormal 2

55. Prostate Size (Grade I,II,III,IV)

56. PVR Insignificant 0 Significant 1

If in-significant, specify_____________________________________________________

Stone Analysis as and when passed

57. Chemical Analysis

58. X-Ray diffraction

Date: _____________ Signature of the Investigator_______________________

VECTOR BORNE DISEASES

SEC

TIO

N - X

III

770

Blank

771

ASSESSMENT OF THE THERAPEUTIC EFFICACY OFCERTAIN HERBAL / HERBOMINERAL DRUGS IN

THE MANAGEMENT OF KALA-AZAR

Drug: Study Code:



772

Blank

773


ASSESSMENT OF THE THERAPEUTIC EFFICACY OF CERTAIN HERBAL /HERBOMINERAL DRUGS IN THE MANAGEMENT OF KALA-AZAR

I. BACKGROUND

The disease Kala-azar also known as Visceral Leishmaniasis is a highly fatal diseasecaused by Leishmania donovani. The origin or entity of the disease may not be historic butaccording to classical literature may be correlate with same of the symptoms found resembleswith ‘SATATAK JWAR’ under the group of Vishamajwara. Though the Visceral Leishmaniasis iscaused due to the bite of sandflies transporting the organism / parasite Leishmania donovani whichis not described in Ayurveda but the causative factor of ‘SATATAK JWARA’ may be correlatedwith ‘Bhutabhisanga’. Then probably Leishmania donovani might have been discovered by presentera. However the sign & symptoms like spleenomegaly (Pleihavriddhi). Fever (Mandajwara).Vishamarambha is the cardinal symptoms in ‘SATATAK JWARA’ upon which Kala-a-zar may betaken as in prevalence with modern synonyms.

In India, man is the reservoir of infections, and parasite are readily obtainable fromperipheral blood by the sand fly (rodents and dogs are the main reservoir hosts in African venerealleishmaniasis). Visceral Leishmaniasis may occur in epidemics and recording of epidemic outbreaksin India goes to year 1870.

Keeping in the view and considering these above aspect, the persistent morbidity, highmortality and high toxicity of present available modern drugs especially Pentamedin,Amphotericin‘B’ and Sodium stibogluconate etc. and some herbo-mineral compound has beenshorted out for the management of Kala-azar and aspecting the probable results due to containingAntimony sulphide (modern drug of choice) i.e. Srotonjana.1

Apart from this some Hepato-protective and Spleeno-protective, Heamatinic, febrifugeherbal drugs i.e. Guduchi, Sharpunkha, Kalmegha, Rohitaka, Sakhotaka, Saptaparna, Sudarshanaand Punarnava etc. are possible suitable Ayurvedic drugs in this ailment and this project has beenselected for clinical trial.

References :1. Pandit.Kasinath Sashtri and Dr. Gorakhanath Chaturvedi (1984) Charaka Samhita, (text with

Hindi commentary) XIIth Edition (1984), Published by Chaukabha Vidhya Bhavan, Varanasi,

India2. Harisson’s Principles of internal medicine, Volume-1, 14th Edition, International Editions, 1998,

Published by McGraw-Hill CompaniesInc.

3. Ambika Dutta Sashtri(1989), Susruta Samhita (text with Hindi commentary), VIIth EditionChaukhamba Sanskrit Series Office, Varanasi

774

II. OBJECTIVE

To evaluate the efficacy of some Herbal / Herbomineral drugs in the management of Kala-Azar.

III. CENTRE

CCRAS centers in collaboration with other centers.


Sample size- 300

Groups –

Group Total Cases Drug & Dose

Group – I (Treated group) 150

Group – II (Treated group) 100

Group – III (Control group) 50 Amphotericin’B’

(Treated with modern medicines)

Allocation of the cases in each group will be made on randomize by a statistician.

Treatment: Some Herbal / Herbomineral drugs

Design of study: Open trial with standard control group.

Duration of study: 2 years ( 1 year for treatment and 1 year for follow up)

Total period of study: 2 years


1. Age – 10 to 60 years

2. Sex both male & female

3. Positive cases of Kala-azar (Leishmania donovani in spleen / bone marrowaspirate )

4. Clinical diagnosis of active VL (visceral leishmaniasis) with consistent signs &symptoms (e.g. Fever & spleenomegaly)

5. Haemoglobin 5 gm / dl

6. WBC > 1500/mm3

775


1. Age below 10 yrs & above 60 yrs.

2. Pulmonary tuberculosis

3. Severe Jaundice / Hepatitis

4. Pregnancy / Lactating mother

5. HIV positive serology / Malignancy

6. Any other serious systemic disease.

7. Hepatic-spleenomegaly due to other diseases.

8. History of Renal disease / Cardiac disease.

VII. CRITERIA FOR WITHDRAWL FROM STUDY

During the course of the trial treatment, if any serious condition or any serious adverseevents which requires urgent treatment or if patient himself want to withdrawn from the study, suchsubject may be withdrawn from the trial and managed by the principal Investigators accordingly

VIII. ROUTINE EXAMINATION & ASSESSMENT

A detailed clinical history and physical examination of each patient will be recorded as perproforma (From I & IA). The clinical pathological, Biochemical and other lab investigation will bedone before treatment, during treatment period and at the end of the treatment will be carried outas per recorded in the proforma. The assessment of the results will be done on the basis ofdisappearance of L.D. bodies and improvement in clinical features.



X. CRITERIA OF ASSESSMENT

1. Disappearance of parasite (L.D. bodies)

2. Absence of Pyrexia & other clinical symptoms.

3. Negative L.D. bodies in bone marrow / spleen aspirate found at the end oftreatment (clinical improvement), smear stained for demonstration of Leishmaniadonoveni bodies (L.D. Bodies).

776

4. Culture Aspirates (for L.D. Bodies) of the following

5. Aldehyde Test

6. R.K. 39 Kit test

7. Urea stibamin test

XI. TRIAL MONITORING AND DATA ANALYSIS:-

The monitoring of progress of the trial and data analysis will be undertaken by CCRAS,H.Q. New Delhi.

XII. ETHICAL REVIEW

Each Institutional Ethical Committee (IEC) of participating centers should give clearancecertificate before the project initiated. Patient’s information sheet and informed consent form shouldbe submitted along with project proposal for approval by IEC. Both should be maintained induplicate with one copy given to the patient at the time of entry of trial. The study will beconducted in accordance with Good Clinical Practice.

XIII. TRAVELING EXPENSES FOR RESEARCH SUBJECTS:

A consolidated amount of Rs…../- per visit will be paid to subject.





777


ASSESSMENT OF THE THERAPEUTIC EFFICACY OF CERTAIN HERBAL /HERBOMINERAL DRUGS IN THE MANAGEMENT OF KALA-AZAR


CERIFICATE BY INVESTIGATOR


Date: …………………… Signature …………………..

Name ………………………

CONSENT BY SUBJECT

I have been informed to my satisfactory, by the attending physician, the purpose of theclinical trial and the nature of drug treatment and follow-up, including the laboratory investigationsto be performed to monitor and safeguard my body functions.


I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “Assessment of the Therapeutic efficacy of certain Herbal / Herbomineraldrugs in the management of Kala-azar.”

Date: ………… Name of the Subject: ………………..................

Signature or Thumb impression…………….........

Date: ………… Name of witness: ……………………….............

Signature or Thumb impression: ………...............

Relationship ……………………………..............

To be translated into regional language

778


ASSESSMENT OF THE THERAPEUTIC EFFICACY OF CERTAIN HARBAL /HERBOMINERAL DRUGS IN THE MANAGEMENT OF KALA-AZAR



The available treatment for Kala-azar in modern medical science like amphotericin’B’,sodium stibogluconate etc. Modern medicine have made tremendous success in providing the reliefbut is drug resistence & adverse effects are found in treatment. In Ayurveda, certain Herbal /Herbomineral drugs that have been in practice as well as have shown anti-kala-azar effect havebeen taken up for the study.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 7 days to complete. During thisperiod, you are expected to visit the hospital for clinical and physiological assessment.

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination, & R.K.-39 test, spleen-bone marrow aspirate for L.D. body and otheressential lab-investigations of blood and urine samples will also be taken. This is to make sure thatyou are eligible for the study.

If you are eligible, you would be put on trial treatment for Kala-azar. During visit, youwill be supplied with sufficient quantities of drugs to last until your next visit. If any adversereactions like skin allergy, nausea, vomiting and palpitation / tremor etc., noticed during thetreatment period, this should be noticed to the Principal Investigator.

Advice: (To be given along with Patients Information Sheet)

1. To avoid trigger factors like allergens if known.

2. To avoid respiratory irritants like tobacco, smoke and chemicals.

3. To have warm and fresh food and drinks.

Sympathetic discussion of the problem with the patient and assurance.


779


CLINICAL EVALUATION OF SINGLE / COMPOUND HERBO /HERBOMINERAL COMPOUND DRUGS IN THE MANAGEMENT OF

KALA-AZAR


BEFORE TREATMENT

(Enter a √√√√√ in the appropriate box)

1. Name of the Subject: …………………………………........……………………………

2. Address …………………………………………………….......……………………….

3. Centre…………………………………




7. Group: Treatment Treatment Control

CRITERIA OF SELECTION Yes(1) No(0)

1. Age 10 to 60 yrs.

2. Positive Symptoms of Kala-azar (L.D. bodies)

3. Fever

4. Enlarged spleen

CRITERIA OF EXCLUSION Yes No

5. Age below 10 yrs and above 60 yrs.

. Pulmonary Tuberculosis

7. Severe Jaundice

8. Pregnancy

9. Malignancy

Any other severe systemic disease

Date: …………………… Signature of the Investigator: …………………..

780


CLINICAL EVALUATION OF SINGLE /COMPOUND /HERBO /HERBOMINERAL COMPOUND DRUGS IN THE MANAGEMENT OF

KALA-AZAR


(Enter a √ √ √ √ √ in the appropriate box)

1. Name of the Subject: ………………………………………….......……………………

2. Address ……………………………………………………………......……………….


4. Centre…………………………




8. Date of admission: Date of discharge:


10. Educational status: Illiterate (1) 1 Read and Write (2) 2

Primary School (3) 3 Middle School (4) 4

High School (5) 5 College (6) 6

Other (specify) (7) 7 I.N.A. (8) 8




Indicate nature of work: ..................................................................................................

12. Total income of the family in Rupees: ______________________


781

14. Income per capita per month in rupees: ____________________


Christian 4 Parsi 5

16. Marital status Married 1 Unmarried 2 Widow 3

Divorced 4 Widower 5

17. Result: Good Response 1 Fair Response 2

Poor Response 3 No Response 4

Drop out 5 LAMA 6

Death 7

CHIEF COMPLAINTS WITH DURATION (in days)

Fever Present Absent Duration

18. With / without chill

19. Low grade (Patient remaining ambulant intermittent

20. With sweating

21. Double rise in 24 hours

22. Diarrhoea

23. Pain in abdomen

24. General Weakness

25. Bleeding (site)


26. Onset of disease: Acute (1) Insidious (2)

27. Duration of disease (in days):

28. Treatment given so far: Ayurvedic medicine Modern medicine

Unani Homeopathy

Mixed

782

Spell out the medicine given and results obtained: _______________________________

PREVIOUS MODERN TREATMENT (if any)

Drug Total quantity Duration Response

29. Pentavalent Antimony _____________________

30. Pentamidin / Lomidin _____________________

31. Allopurinol _____________________

32. Anti-tuberculosis _____________________

33. Other _____________________

34. Factors aggravate the disease / chief complaint:

Drug Diet Cold climate Tropical climate

Damp climate Sea sore

Positive factors may be spell out ……………...........................………………………….

35. Factors relieve main complaints:-

Drug Diet Cold climate Tropical climate

Damp climate Sea sore

Positive factors may be spell out ……………...........................………………………

36. Past illness, having relation with present illness: Yes No

Family History Yes (1) No (0)

37. Hypertension

38. Diabetes Mellitus


40. Mental disease

41. Cancer

42. Cardio Vascular disease

783

43. Tuberculosis

44. Others (specify) ………………………………….......................………………………..

Personal History

45. Diet: Veg Non-veg Lacto-ova veg


47. Emotional stress: Yes No

48. Bowel habit Regular Constipation

Hard stool Loose stool

49. Sharira Prakriti Vata Pitta Kapha


Sama

50. Manasa prakriti Satva Rajas Tamas

Satva- rajas Satva-tamas Rajas- tamas

Sama

51. Addiction: Yes No

If yes specify …………………....................……………………………………………


52. Built: Lean Medium Heavy


54. Body weight (Kg): ___________________________

55. Blood pressure (Systolic) ___________________________

56. Blood pressure (Diastolic) ___________________________

57. Body temperature ___________________________

58. Pulse rate per min. ___________________________

784

59. Respiration per min. ___________________________

Yes No

60. Pallor

61. Jaundice

62. Emaciation

Present Absent

63. Lymphadenopathy

If present indicate group …………………..................................……………………….

64. Increased pigmentation of the skin

If yes specify: On face ________________ Other part ____________

Normal Abnormal

65. Hair distribution

If abnormal specify …………………................................……………………………..

66. GumsIf abnormal specify ………….................................………….............…………….........


Abdomen

67. Shape: Normal Abnormal

68. Distention : Present Absent

If present indicate ……................................…………………………………………..

69. Distended veins: Present Absent

70. Umbilicus: Normal Abnormal

If Abnormal specify ……….................................................……………………………….

71. Tenderness : Yes No

If yes specify ………………………...................................…………………………….

72. Rigidity: Present Absent

785

If present then specify ……………….......................................................……………

73. Spleen: Mild Moderate Massiveenlargement

74. Spleen-consistency Soft Hard Firm

75. Liver Enlarged: Yes No

If yes then indicate the measurement in cm

76. Kidney: Palpable Not Palpable

77. Any other abdomen Masses: Palpable Not Palpable

78. Ascities: Present Absent

Normal Abnormal

79. Hernial Orifices:

If abnormal, specify abnormalities ……………………………………….......………….

80. C.V.S. with chest

If abnormal, specify abnormalities …………………........……………………………….

81. C.N.S.

If abnormal, specify abnormalities ………………………........………………………….


If abnormal, specify abnormalities ……………………………........…………………….

Samprapti (Pathogenesis) of the disease according to Ayurvedic concept

Vata Pitta Kapha


84. Anubandha dosha

85. Avraka dosha

86. Ksheena dosha

87. Ksheena dhatu: Rasa Rakta Mamas Meda

Asthi Majja Shukra Ojas

786

88. Dushya Involved: Rasa Rakta Mamas Meda

Asthi Majja Shukra

89. Stages of disease (Roga Kriya Kala): Sthana – Sanshraya Sanchaya

Prakopa Prasar

Vyakti Bheda

Srotas Examination Yes No

90. Annavaha Srotas

Anannabhilasha (Loss of appetite)

Aruchi (Anorexia)

Avipaka (Indigestion)

Chhardi (Vomiting)

91. Prana Vaha Srotas

Alpa Alpa Swasa (Dyspnoea)

Atisarana Swasa (Increased Respiration rate)

Abhikshna Swasa (Chyne Stroke Breathing)

Kupita Swasa (Vitiated, breathing)

Shashula Swasa (Dyspnoea with pain)

92. Udak Vaha Srotas

Jihva Shosha (Dryness of tongue)

Dusth Shosha (Dryness of lip)

Talu Shosha (Dryness of palate)

Kanth Shosha (Dryness of buccal cavity)

Kloma Shosha (Excessive thirst)

Trishna (Feeling of thirsty)

787

Yes No

93. Pureeshavaha Srotas

Alpa alpa purisha (Not clear, repeated, scanty defecation)

Sashoola Purisha (Painful defection)

Atidrava pureesha (Diarrhea)

Atigrathita pureesha (Scybala)

94. Mutravaha Srotas

Bahumatrata (Polyurea)

Atibandhata (Scanty urination)

Prakupita Mutrata (Difficulty in urination)

Alpa Alpa Mutrata (Scanty urination)

Abhikshna Mutrata (Constant/repeated -urination)

Bahul Mutrata (Urine with prostatic secretia)

Sashoola Mutrata (Dysuria)

95. Svedavaha Srotas

Aswedana (Dryness of skin)

Atiswedana (Profuse sweating)

Parushya (Roughness of skin)

Lomaharsha (Erection of hair follicle)

Angaparidaha (Burning sensation in the body)

Yes No

96. Rasavaha Srotas

Mukha Vairasya (Bad test in mouth)

788

Arasajnata (Testelessness)

Hrillasa (Nausea)

Gaurava (Feeling heaviness)

Tandra (Drowsiness)

Angamarda (Body cramps)

Jvara (Fever)

Pandu (Anaemia)

Avasada (Lassitude)

Klaivya (Sexual inadequacy)

Karshya (Emaciation)

Agnimandya (Diminished appetite)

97. Rakta Vaha Srotas

Pidika (Boils)

Raktapitta (Bleeding from any of the orifice)

Mukhapaka (Stomatitis)

Vidradhi (Absess)

Charma Roga (Skin disease)

Kamala (Jaundice)

Yes No

98. Mamsa Vaha Srotas

Arbuda (Tumor)

Alajee (conjunctivitis)

Gandamala (Cirvical Lymphadinitis)

Upajivihika (Epiglotitis)

Adhimansa (Protuberance of flesh/Cancer/Cyst)

789

99. Medovaha Srotas

Maladhikya (Excess of excreta)

Hastapadadaha (Burning sensation in the sole & palm)

Hastapadasunata (Numbness of the limbs)

Tandra (Drowsiness)

Dehachikkanata (Greasiness of the skin)

Alasya (lethargy)

100. Asthivaha Srotas

Adhyasthi (Hypertrophy of bone)

Adhidanta (Redudant tooth)

Dantashoola (Toothache)

Asthishoola (Tenderness of bone)

Kesha, Loma, Nakha, Smashru Vikar

(Any defects of hair, hair follicle, nail and mustaches)

101. Majja Vaha Srotas

Parvashoola (Pain in the Inter-phalangeal joint)

Bhrama (Vertigo/Giddiness)

Murchha (Syncope)

Mithyagyana (Illusion)

102. Sukravaha Srotas

Klaivya (Sterlity / Impotency)

Aharshana (Loss of erection)

Garbhapata (Abortion)

790

Santana Vikriti (Congenital deformity of the children)

103. Artavavaha Srotas

Anartava (Amenorrhoea)

Vandhyatva (Sterility)

104. Provisional Diagnosis :-

105. Final Diagnosis :-

106. Medical Management :-

107. Principal Drug Therapy :-

Dose

Vehicle

Diet

108. Summary of finding :-

Date: ……………. Signature of the Investigator: ……………………………..

791

COUNCIL FOR RESEARCH IN AYURVEDA AND SIDDHA

CLINICAL EVALUATION OF SINGLE / COMPOUND / HERBOMINERALCOMPOUND DRUGS IN THE MANAGEMENT OF KALA-A-ZAR

CASE REPORT FORM III -CLINICAL AND PHYSIOLOGICAL ASSESSMENT(2, 4, 6 & 8 weeks)

(For periodic observation & assessment Parameter to be taken for assessment ofresponse of therapy initially at the time of Admission / Enrollment after starting therapy)

1. Name of the Subject: ………………………………………………….........……………

2. Address ……………………………………………………………………...........…….


4. Centre…………………………




8. Date of admission: Date of discharged:


1. Clinical Parameter

Before Treatment After Treatment

2 weeks 4 weeks 6 weeks 8 weeks

a) Subjective symptoms

1. Fever

2. Loose motion

3. Pain abdomen

4. Weakness

5. Bleeding

792

b) Objective signs

1. Temperature

2. Pallor

3. Anemia

4. Emaciation (Body wt.)

5. Pulse rate

6. Lymphadenopathy

7. Increased pigmentation of the skin

8. Enlargement of spleen

9. Enlargement of liver

10. Measurement of girth of abdomen.

Date: …………………….. Signature of the Investigator: ……………………….

793


CLINICAL EVALUATION OF SINGLE / COMPOUND / HERBOMINERALCOMPOUND DRUGS IN THE MANAGEMENT OF KALA-A-ZAR


(2, 4, 6 & 8 weeks)

1. Name of the Subject: ………………………………………….......................……....…

2. Address ……………………………………………………………..............…………..


4. Centre…………………………




8. Date of admission: Date of discharge :


ADVERSE EVENTS



1 2 3 4

Adverse

Experience

794

Date started

Date

Time

Date stopped

Pattern

Isolated-1

Intermittent-2

Continuous-3

Severity

Mild-1

Moderate-2

Severe-3



Serious*

Yes-1

No-2





795

Relationshipto studymedication

Unrelated-1Possible-2Probable-3

Unrelated: A reaction that does not follow a reasonable temporal sequence from theadministration of the drug; or a known adverse reaction pattern of the suspected drugs could



Probable: follows a reasonable temporal sequence from administration of the drug; follows aknown response pattern to the suspected drug; that could not be reasonably explained by theknown characteristics of the patient's clinical state.

796


CLINICAL EVALUATION OF SINGLE / COMPOUND / HERBOMINERALCOMPOUND DRUGS IN THE MANAGEMENT OF KALA-AZAR


1. Name of the Subject: …………………………………………........……………………

2. Address …………………………………………………………….......……………….


4. Centre…………………………




8. Date of admission: Date of discharge :


Investigation at the sample taken At the After 15 After 45 After 60

time of days days days

admission

1 2 3 4

Urine

10. Sugar: ……………………....……

11. Albumin: …………………………

12. Pus cell: …………………………

13. Cast: ……………………….........

14. RBC: ………………………....…

15. Bile salt: …………………….…..

16. Bile pigment: …………………....

797

Stool

17. Ova: ……………………..............….......…

18. Cyst: ……………….................……........…

19. Occult blood: ………………………….......

20. Stercobiline: ………………………...….......

21. Sputum A.F.B: ………………………….....

HAEMATOLOGICAL INVESTIGATION

Blood

22. Hb.% : …………………….........................

23. T.L.C.(In thousands) : ……………………..

24. D.L.C.: P (%): ______ L (%) ______ B (%) _______ M (%) _______ E (%) _______

25. E.S.R.: ………………….............................

26. P.C.V.: ………………………......................

27. M.C.V.: ………………………....................

28. Platelate count: …………………….........…

29. Reticulo Cyte: …………..……....................

Count: ………………………......................

(In thousands)

30. B.T.: …………………….........................…

31. C.T.: ………………………….....................

32. P.T.: ………………………......................…

33. T. Protein: ………………………................

34. A/G ratio: ……………………….............…

35. F.B.S.: …………………………..................

36. P.P.B.S.: ………………...............…………

37. S. Bilirubin: …………………..........………

798

38. S. Alkaline Phosphatase: ……………..……

39. S.G.O.T.: ………………………..............…

40. S.G.P.T.: ………………………...............…

RADIOLOGICAL INVESTIGATION

42. X-Ray Normal Abnormal

Chest

Parametric investigations (for Kala-azar)

43. Smear stained for demonstration of Leishman Donovan bodies

Positive Negative

1. Aspirates of

a) Bone marrow

b) Spleen

c) Liver

d) Lymph gland

2. Culture of aspirates (for L.D. bodies) of the following

a) Bone marrow

b) Spleen

c) Liver

d) Lymph gland

3. Aldehyde test: ……………………....……..

4. Urea stibamin test: …………………....……

5. R.K. 39 – Kit test: …………………….….


799

ASSESSMENT OF THE EFFICACY OF CERTAINHERABL / HERBO-MINERAL DRUGS IN THEMANAGEMENT OF SLEEPADA (FILARIASIS)

Drug: Study Code:



800

Blank

801


ASSESSMENT OF THE EFFICACY OF CERTAIN AYURVEDIC / HERBO-MINERAL DRUGS IN THE MANAGEMENT OF SLEEPADA

(FILARIASIS)

I. BACKGROUND

The control of the disease is dependent on the control of mosquito breeding andelimination of the intermediate host Culexfatigans. It is a global problem. References of this isfound in Ayuervedic text book where in it has been described as a swelling of legs and feet dueto vitiation of Mamsa & Rakta by Kapha Dosha. The detailed description of the disease, coveringclinical features, etio-pathogenesis, the different types, the prognosis and the epidemiological detailsof the disease have been provided. The treatment of this disease is Siravedh and Kaphanashakremedies as described in Charak Samhita.

The characteristic features of the disease are the onset of painful swelling in groins withfever which gradually descends down to leg & foot. The other parts of the body may be affectedthrough scrotum in male and breast in female. It is further stated that though the disease may bedue to the involvement of all three doshas, but the predominance of Kapha is obvious in all thethree varities.

This disease is a result of the infestation of filarial parasite, Wuchereria bancrofti. Thefrequency of this disease is very much related to the situation where mosquito breeding is moreprevalent. The mosquito Culex fatigans is of crucial importance in the life cycle of filarial parasite.

Ayurveda has also recognized this disease from very earliest time and its description andtherapy have been developed in this system. In Ayurvedic literatures so many herbal &herbomineral drugs are mentioned viz. Guduchi, Punarnava, Saptaparna, Sharapunkha, Rohitakaetc., as herbal preparation & Nityodit Rasa, Slipadari Rasa, Kanchnara Guggulu, GokshuradiGuggulu etc. as compound herbomineral formulations for the treatment of Sleepada.

References1. Pandit.Kasinath Sashtri and Dr. Gorakhanath Chaturvedi (1984) Charaka Samhita, (text with

Hindi commentary) XIIth Edition (1984), Published by Chaukabha Vidhya Bhavan, Varanasi,

India.

2. Ambika Dutta Sashtri(1989) Susruta Samhita (text with Hindi commentary) VIIth EditionChaukhamba Sanskrit Series Office, Varanasi.

3 Shri Pandit Lal Chandra vaidya (1963), Astanga Hridya ((text with Hindi commentary), Moti Lal

Banarsi Das Publication, Varanasi4. Harisson’s Principles of internal medicine, Volume-1, 14th Edition, International Editions, 1998,

Published by McGraw-Hill CompaniesInc.

802

(filaria). The objective of this study are the assessment of some certain herbal / herbo-mineralcompound preparation in the management of Sleepada (filaria) and to assess the importance ofherbal drugs for the management of the challenging problem ‘Sleepada’

II. OBJECTIVE

To assess the efficacy of certain Herbal / Herbo-mineral drugs in the management ofSleepada (Filariasis)

III. CENTRE


IV. SAMPLE SIZE AND METHOD

Sample size — 200 (100 patients in each group)

Treatment — Herbal / Herbo-mineral drugs

Design of the study — Single blind

Period of Study — 1 month


1. Age – 10 to 60 years.

2. Sex – both male & female

3. Positive case of Filaria

4. Patients having clinical features like Lymphadenities, Lymphangitis, Lymphodema, deformity,chylurea & fever will be selected irrespective of positive blood smear of microfilaria.


1. Age below 10 yrs & above 60 yrs.

2. Patients having nodular deformity, wound, ulcer, thorny deformity, anthill like deformity,nutritional odema, odema due to renal problems, cardiac disorder & arthritis disorders.

3. Any other serious systemic disease like – Pulmonary tuberculosis, Jaundice, HIV positivecases / Malignancy.

4. Pregnancy & Lactating mother.

803

VII. CRITERIA FOR WITHDRAWL

During the course of the trial treatment, if any serious conditions or any serious adverseevents which requires urgent treatment or if patient himself want to withdrawn from the trial andmanaged by the principal investigators accordingly.

VIII. ROUTINE EXAMINATION & ASSESSMENT:-

A detailed clinical history and physical examination of each patients will be recorded asper proforma (from I & IA). The Clinical, Pathological, Biochemical & other Lab investigation willbe done before treatment, during treatment and at the end of treatment will be carried out as perrecorded in the proforma. The assessment of the result will be done on the basis of disappearanceof M.F. and improvement in the clinical features.



X. CRITERIA FOR ASSESSMENT OF THERAPY

Response Assessment Criteria

1. Good Response — 75 % & above relief in symptoms

2. Fair Response — 50 % & 74% above relief in symptoms

3. Poor Response — 25% , 49% & 25% above relief in symptoms.

4. No Response — No relief in symptoms or other wise withdrawnfrom the study.


The monitoring of progress of the trial & data analysis will be undertaken by CCRAS,New Delhi.

XII. ETHICAL REVIEW

1. Ethical Committee (IEC): The proposal will be placed before Ethical Committee (IEC)of trial center for getting clearance certificate before the project is initiated. Patient’sinformation sheet and informed consent form will be submitted along with project proposalfor approval by EC. Both will be maintained in duplicate with one copy given to thepatient at the time of entry to the trial.

2. Data and Safety Monitoring Board: A Data and safety monitoring board (DSMB) atHqrs will carefully monitor the data and side effects during the period of study and put in

804

a place where by prompt reporting of adverse events occur. The data will be reviewed asevery 20 participants entered the study and administered the trial drugs. The researchteam will report immediately to the PI and Data Monitoring Board 1) any life threateningconditions whether they are perceived to be study related or not. The Board decideswhether the adverse effects warrant discontinuation of the study protocol. Protocols will bewritten and approved for the treatment of study related adverse events




Short-term two-day training will be provided to the Investigators and Laboratorypersonnel involved in the multi-centric trial at CCRAS Hqrs. and Central Research Institute(Ay.), New Delhi. The investigators and technicians will be detailed about the clinical trialconduct and laboratory procedures in order to maintain the uniformity.


The Laboratory Investigations (Pathological/Biochemical, etc.), which are not available atresearch Institutes should be conducted at identified reputed labs /Government Institutesunder intimation to this Council following codal formalities.

805


ASSESSMENT OF THE EFFICACY OF CERTAIN HERBAL / HERBO-MINERAL DRUGS IN THE MANAGEMENT OF SLEEPADA (FILARIASIS)




Date: ……………… Signature of the subject: …………..........………………

Name …………………………………….........………..

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “Assessment of Safety & Therapeutic Efficacy of Certain Ayuervedic /Herbal / Herbomineral drugs in the management of Sleepada (Filariasis).”

Date: ……………….. Name of the Subject: …………….............…………..…

Signature or Thumb Impression …………................……

Date: ……………….. Name of Witness: ……………….................….………...

Signature or Thumb Impression: ......……….............……

Relationship …………………………………...............…


806

ENTRAL COUNCIL FOR RESEARCH IN AYURVEDA AND SIDDHA

ASSESSMENT OF SAFETY & THERAPEUTIC EFFICACY OF CERTAINAYUERVEDIC / HERBOMINERAL DRUGS IN THE MANAGEMENT OF

SLEEPADA (FILERIASIS)



The available treatment for Sleepada (Filariasis) in modern medical science like drugsHetrazan, Banocide forte etc. have made tremendous success in providing instant or symptomaticrelief but there is recurrent acute exacerbation and remission. In Ayuerveda, many drugs seem topossess a anti Filarial effect of which certain Ayuervedic / Herbal / Herbomineral drugs that havebeen in practice as well as have shown anti Filarial effect have been taken up for the study.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 3 months to complete. During thisperiod, you are expected to visit the hospital 6 times for clinical and physiological assessment.

Before you start treatment, during the first visit to the clinic you will undergo a completephysical examination, ECG and X-ray, Blood, MF test and urine samples will also be taken. Thisis to make sure that you are eligible for the study.

If you are found eligible, you will be supplied with sufficient quantities of drugs to last untilyour next visit. If any adverse reactions like skin allergy, nausea, vomiting and palpitation/tremoretc., noticed during the treatment period, this should be noticed to the Principle Investigator.

Advice: (To be given along with Patients Information Sheet)

To avoid trigger factors like allergens if known.

To avoid respiratory irritants like tobacco, smoke and chemicals.

To have warm and fresh food and drinks.

Sympathetic discussion of the problem with the patient and assurance.


807


ASSESSMENT OF SAFETY & THERAPEUTIC EFFICACY OF CERTAINHERBAL / HERBOMINERAL DRUGS IN THE MANAGEMENT OF



(Enter a √ in the appropriate box)

1. Centre: ………………..……….........


3. Name of the subject: ………………………………………….....………………………

4. Address ……………………………………..…………………….....………………….



7. Date of admission:

8. Date of discharge:

9. Group No.: First Second Third Fourth


1. Age – 10 to 60 years.

2. Sex – both male & female

3. Positive case of Filaria

4. Patients having clinical features like Lymphadenities

5. Lymphangitis

6. Lymphodema

7. Deformity

8. Chylurea

9. Fever

808


10. Age below 10 yrs & above 60 yrs

11. Nodular deformity

12. Wound

13. Ulcer and thorny deformity

14. Anthill like deformity

15. Nutritional odema

16. Odema due to renal problems

17. Cardiac disorder

18. Arthritis disorders.

19. Pulmonary tuberculosis

20. Jaundice

21. HIV positive cases/Malignancy

22. Pregnancy & Lactating mother



Date: ………… Signature of the Investigator:.,…………………….

809


ASSESSMENT OF SAFETY & THERAPEUTIC EFFICACY OF CERTAINHERBAL / HERBOMINERAL DRUGS IN THE MANAGEMENT OF SLEEPADA

(FILERIASIS)



1. Centre: …………….........…........….


3. Sr. No. of the subject: ……………………………...

4. Name of the subject: ……………………………….............……………………………

5. Address ………………………………..…………………….............………………….





10. Educational status: Illiterate 1 Read and Write 2

Primary School 3 Middle School 4High School 5 College 6Other (specify) 7 I.N.A. 8

11. Occupation: Desk work 1 Field work 2 Student 3Housewife 4 Others 5

Indicate nature of work: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12. Income per capita per month (in Rs.)

Less than Rs.5000/- (1) More than Rs.-5000/-

Chief Complaints with duration (in days)


13. Lymphadenitis

810

14. Lymphangitis


15. Lymphoedema

16. Deformity

17. Chylurea

18. Fever

19. Rigor

20. Pain in affected part of the body

21. Heaviness of the affected

part of the body




24. Treatment given so far: Ayurvedic medicine Modern medicine

Unani Homoeopathy

Medicines given…………………….. Result obtained ………………….

25. Factors aggravate the disease / chief complaint:

Drugs Diet Cold climate

Tropical climate Damp climate Sea shore

Others (specify) ……………………………….......……………………………………

Positive factors may be spell out ………………….....…………………………………

26. Factors relieved main complaints:

Drugs Diet Cold climate


Others (specify) ………………………………….....……………………………………

Positive factors may be spell out …………………......…………………………………

811

27. Past illness, having relation with present illness: Yes No

If yes, specify ……………………………………………….....……………………..

Family History Yes (1) No (0)

28. Hypertension

29. Diabetes Mellitus


31. Mental diseases

32. Cancer

33. Cardio vascular disease

34. Tuberculosis

Personal History :

35. Diet: Veg Non-veg Lacto-ova-veg


37. Emotional stress: Yes No

38. Bowel habit Regular Constipation

Hard stool Loose stool

39. Prakriti: Vataja Pittaja Kaphaja

Vata-Kaphaja Vata-Pittaja Pitta-Kaphaja

Sannipataja

40. Mans Prakriti: Satva Rajas Tamas

Satva-Rajas Stava- Tamas Rajas-Tamas

Sama

Yes (1) No (0)

41. Tobacco smoking exposure

If yes specify whether it aggravated the symptoms or not: ……………….....................…………

812

42. Tobacco chewing

If yes specify: (a) Quantity ____________

(b) Total duration in years: ____________

43. Betel chewing

44. History of alcohol intake:

Occasional : 1

Regular : 2

Never : 3

Physical Examination:



47. Height (cm): ____________

48. Weight (kg) ____________

49. Weight (kg.) ____________

Height (meters)2

50. Pulse (per min) ____________

51. Blood Pressure (mm Hg) ____________

52. Body temperature (o F) ____________


54. Cyanosis ____________

55. Clubbing nails ____________

56. Edema ____________


57. Cynosis

B.M.I ={ }

813

58. Anaemia

59. Jaundice

60. Pigmentation


62. Deformities

63. Lymphadenopathy


Normal Abnormal

66 C.V.S. (with chest)

If ‘abnormal’ specify abnormalities …………....................................................…………

67 C.N.S.

If ‘abnormal’ specify abnormalities ……………...............................................……………

68 Digestive system

If ‘abnormal’ specify abnormalities ……………………............................................……

69 Uro-Genital system

If ‘abnormal’ specify abnormalities ……………………….............................................…

Local Examination of the affected part(s)(As per criteria laid down vide annexure – 1)

S.No. Part(s) affected Swelling Tenderness Appearance /Colour/Consistency

1.

2.

3.

4.

5.

6.

814

Samprapti (Pathogenesis) of the disease according to Ayurvedic concept

64. Anubandhya dosha Vata Pitta Kapha

65. Anubandha dosha Vata Pitta Kapha

66. Avaraka dosha Vata Pitta Kapha

67. Ksheena dosha Vata Pitta Kapha

68. Ksheena dhatu Rasa Rakta Mamsa

Meda Asthi Majja

Shukra Ojas

69. Dushya (Involved) Rasa Rakta Mamsa

Meda Asthi Majja

Shukra Ojas

70. Stages of disease (Roga Kriya Kala) Sanchaya Prakopa

Prasara Sthana Sanshray Vyakti

Bheda

Srotas Pareeksha

71. Prana vaha srota



Abhikshna Swasa (Chyne stroke breathing) 3

Kupita Swasa (Vitiated breathing) 4


72. Udakavaha srota



Talu sosha (Dryness of palate) 3

815

Kantha sosha (Dryness of throat) 4

Kloma sosha (Excessive thirst) 5

Trishna (Thirst) 6

73. Annavaha srotas


Aruchi (Anorexia) 2






Hrillasa (Water brash) 3


Tandra (Stupor) 5


Jwara (Fever) 7

Pandu (Anaemia) 8

Avasada (Depression) 9

Klaibya (Loss of libibo) 10




Pidika (Boils) 1


Mukha Paka (Stomatitis) 3


816

Charma roga (Skin disease) 5

Kamala (Jaundice) 6


Arubuda (Tumour) 1

Alajee (Phlyctenular conjunctivitis) 2

Gandamalaa (cervical lymphadenitis) 3

Upji (Epiglotis) 4







Tandra (Stupor) 4


Alasya (Lethargy) 6


Adhyasthi (Hypertrophy of bone) 1


Dantashoola (Toothache) 3

Asthi shoola (Bone pain) 4

Kesha, loma, nakha, samshru vikara 5(Any defects of hair, hair follicles, nails and mustaches)

79. Majja vaha srotas



817

Moorchh (Syncope) 3


80. Shukra vaha srotas

Klaivya (Sterility / impotence) 1



Santana Vikriti (Congenital deformity of the children) 4

81. Manovaha srotas

Manovibramsha 1

Budhivibramsha 2

Sanjna Vibhramsha 3

Smritivibhramsha 4

Bhaktivibhramsha 5

Sheelavibhramsha 6

Chesta Vibhramsha 7

Acharavibhramsha 8



Vandhyatva (Sterility) 2


Bahumutra (Polyuria) 1

Atibadhata (Urination with obstruction) 2

Prakop-mutra (Defective Urination / Difficulty 3in micturition)


Aabhikshna (Constant / repeated urination) 5

818

Bahulamutrata (Urine with prostatic secretion) 6

Sashoola amutrata (Painful micturition) 7


Alpaalpa Pureesha (Scanty defecation) 1

Sashoola Pureesha (Painful defecation) 2

Atidrava Pureesha (Diarrhoea) 3

Atigrathita Pureesha (Scybala) 4


Aswedana (Loss of perspiration) 1




Angaparidaha (Burning sensation in the body) 5

86. Provisional Diagnosis

87. Final Diagnosis

88. Medical Management

89. Principal drug therapy

Dose

Vehicle

Diet

90. Summary of finding

Date: ……………… Signature of Investigator

819




CASE REPORT FORM – III CLINICAL ASSESMENT

1. Centre: ……………….……….


3. Sr. No. of the subject: ……………………….……..

4. Name of the subject: ………………………………………………………................…

5. Address ………………………………..………………………………………................





INITIAL Weeks after starting therapy

1 2 3 45 6

1. Clinical Parameters

a). Lymphadenitis

(i)

(ii)

(iii)

(iv)

b). Lymphangitis

(i)

(ii)

820

(iii)

(iv)

c). Lymphoedema

(i)

(ii)

(iii)

(iv)

d). Deformity (Score with measurement in cms.)

(i)

(ii)

(iii)

(iv)

(v)

(vi)

e). Pain

(i)

(ii)

(iii)

(iv)

f). Tenderness

(i)

(ii)

(iii)

(iv)

g). Fever

(i)

821

(ii)

(iii)

(iv)

h). Rigor

(i)

(ii)

(iii)

(iv)

2. Laboratory Investigation

i) Microfilaria

ii) Chyle

iii) M.F. Count per 20 Cu.mm

In night blood/ DECP Test

iv) Immunoglobulins

Date: …………….. Signature of the Investigator: ………………….....……….

822




CASE REPORT FORM III A - ADVERSE EVENTS RECORD(0, 15, 30, 45, 60, 75, 90 days)

1. Centre: ………………............…….


3. Sr. No. of the subject: ……………………………..

4. Name of the subject: ……………………………………………............………………

5. Address ………………………………..……………………………….............……….





ADVERSE EVENTS



1 2 3 4

Adverse

Experience

823

Date started

Date

Time

Date stopped

Pattern

Isolated-1

Intermittent-2

Continuous-3

Severity

Mild-1

Moderate-2

Severe-3


Serious*

Yes-1

No-2


824

Relationshipto studymedication

Unrelated-1

Possible-2

Probable-3

Unrelated: A reaction that does not follow a reasonable temporal sequence from theadministration of the drug; or a known adverse reaction pattern of the suspected drugs couldhave been produced by the patients clinical stage, intermittent illness, trauma, accidents etc:



825





1. Centre: ………………..........……….


3. Sr. No. of the subject: ……………………………..

4. Name of the subject: ………………………………………...............……….…………

5. Address ………………………………..……………………………..............………….



Lab. Investigation Before treatment During treatment after

First weeks Second weeks Third weeks Fourth week

8. Date of sample taken

9. Urine

i) Microfilaria

ii) Solublity in ether

iii) Chyle

10. Blood

ii) M.F. Count per 20 Cu.mm.

in night blood smear / DECP Test.

iii) Hb%

iv) T.L.C.

v) D.L.C.

Polymorph : …………………………

826

Lymphocyte : …………………………

Eosinophil : …………………………

Basophil : …………………………

Monocyte : …………………………

vi) E.S.R.

vii) Immunoglobulin

Date: ……………… Signature of the investigator: …………………

827

HAEMATOLOGICAL DISORDERS

SEC

TIO

N - X

IV

828

Blank

829

MULTICENTRIC OPEN CLINICAL TRIAL OFSELECTED DRUGS IN IRON DEFICIENCY ANAEMIA

Drug: Study Code:



830

Blank

831

Reference:1. Charaka, 1962, Charaka Samhita, Chikitsa Sthana Chapter– 16, Choukhamba Sanskrit Series, Varanasi2. A textbook of Preventive and Social Medicine, PARK 15th Edition, 403-404.

3. John W. Adamson, Harrison’s Principles of Int. Medicine, P.660-665.

4. B.C. Mehta, API Text Book of Medicine, 5th Edition reprint, 983-984.5. Harrisson’s Principles of Internal Medicine, Volume 1,15th Edition.

MULTICENTRIC OPEN CLINICAL TRIAL OF SELECTED DRUGS IN IRONDEFICIENCY ANAEMIA

I. BACKGROUND

Iron Deficiency Anaemia1 (which is described under the disease Panduroga in Ayurveda)is a worldwide problem with the highest prevalence in developing countries. It is found especiallyamong women of childbearing age, young children and during pregnancy & lactation. Detaileddescription concerning the etiology, pathogenesis classification and management of Anaemia(Panduroga) is available in classical literatures of Ayurveda.

Iron Deficiency is the most common cause of nutritional Anaemia; others are foliate &Vitamin B-12 deficiency. Iron deficiency can arise either due to inadequate intake or poorbioavailability of dietary iron or due to excessive loss of iron from the body. The poorbioavailability is considered to be major reason for widespread iron deficiency. Women lose aconsiderable amount of iron in menstruation. Some of other factors leading to anaemia areintestinal parasites (hookworm etc.) & malaria.

Current Medical therapy –Prospects

In conventional medicine, various forms of iron viz. Ferrous sulfate, ferrous fumerate etc.are commonly prescribed, but these therapies have their noted adverse effects e.g. nausea,vomiting, abdominal pain, diarrhoea /constipation.

Owing to the gravity of the situation, need is felt for search of safe /effective Ayurvedicoral dosage forms to improve the haemoglobin level in iron deficiency Anaemia. Keeping thegravity of the situation and the public health needs in view, the council has initiated scientificstudies on Dhatri Lauha, a promising formulation that is being successfully prescribed byAyurvedic physicians without any side effects since centuries. The formulation has beenstandardized after formulating SOPs besides safety / toxicity evaluation.

The formulation is found safe and biological activity studies revealed significant haemateniceffect. (Unpublished data of CCRAS) The objective of current study is to assess clinical safetyand efficacy through measurable objective parameters.

832

II. OBJECTIVES

1) Observe the effect of Dhatri lauha on haematological parameters viz. Hb%, MCV,MCHC, TIBC, Serum iron content and Serum ferritin in Iron Deficiency Anaemiasubjects.

2) Observe the clinical safety of Dhatri lauha in Iron Deficiency Anaemia subjects.

III. CENTRE

CCRAS identified Institutes.


Sample size : 40 subjects per Centre

Trial Drug /Dosage /Duration : Dhatri Louha 500 mg. (one capsule) twice dailyafter meal for forty five (45) days with warmwater.

In the pre-treatment phase de-worming should be done with the prescription of onechewable tablet stat of 400 mg. Albendazole, 7 days before the treatment phase to all casesincluded in the trial.


Total period of the study : 1 year (recruitment of Subjects upto the end of 6th

month , continuation of trial therapy till end of 8th

month, last 4 months for compilation of data andstatistical analysis)


1 Age between 15 to 60 years

2 Haemoglobin level between 8 to 10 gm /dl.

3 Serum iron content < 50 ìg /L

4 S. Ferritin < 30 ìg /L

5 MCHC < 34 g/dl

6 MCV <80fL.

7 Peripheral smear of blood shows hypochromic / microcytic anaemia

833



2. Pregnancy and lactation

3. Severe Renal / Hepatic/ Cardiac disease

4. Any continuing blood loss e.g. Haematemesis, Melaena, bleeding piles etc.

5. Dimorphic anaemia


During the course of the trial treatment, if any serious condition or any serious adverseevents which requires urgent treatment or if subjects themselves want to withdraw from the study,such subjects may be withdrawn from the trial.


The full details of screening, history and physical examination of the subjects will berecorded as per case record form I & II. Clinical and physiological assessment in form III andlaboratory investigations in forms IV A, B, C, D will be done at 0, 15th, 30th & 45th daysrespectively. Consolidated data on periodical observation will be recorded in case record form Vat 45th day.


Changes in haemoglobin % (Cyanomethamoglobin method), MCV, MCHC (MeanCorpuscular Haemoglobin Concentration), Serum Iron and Serum Ferritin levels will be consideredfor assessing the outcome of the treatment on 0, 15th, 30th and 45th day. The safety parameters(liver and kidney function tests) will be assessed at 0 and 45th day.





834


A. Institutional Ethical Committee (IEC): The proposal will be placed before InstitutionalEthical Committee (IEC) of trial center for getting clearance certificate before the project isinitiated. Patient’s information sheet and informed consent form will be submitted along withproject proposal for approval by IEC.

B. Data and safety monitoring board: A Data and safety monitoring board (DSMB) atHqrs will carefully monitor the data and side effects during the period of study and put in a placewhere by prompt reporting of adverse events occur and take appropriate steps in case of anyadverse events occur. The data will be reviewed for every 20 participants included into the studyand administered the trial drugs. The research team will report immediately to the PI and DataMonitoring Board if any life threatening conditions whether they are perceived to be study relatedor not. The Board decides whether the adverse effects warrant discontinuation of the studyprotocol. Protocols will be written and approved for the treatment of study related adverse events.


A consolidated amount of Rs. _____ /- per visit i.e., on the 1st day of recruitment afterscreening, 15th day, 30th day and 45th day (4 times)


Short-term two-day training will be provided to the Investigators and Laboratorypersonnel involved in the multicentric trial at CCRAS Hqrs., New Delhi. The investigators andtechnicians will be detailed about the clinical trial conduct and laboratory procedures in order tomaintain the uniformity.


The Laboratory Investigations (Pathological/Biochemical etc.), which are not available atresearch institutes should be conducted at identified reputed Labs /Government Institutes underintimation to this Council following codal formalities.

835




I certify that I have disclosed all details about the study in the terms easily understood bythe subject.

Date: ___________ Signature of the investigator: _______________________

Name ________________________________________

CONSENT BY SUBJECT

I have been informed to my satisfaction, by the attending physician about the purpose ofthe clinical trial and the nature of drug treatment and follow-up, including the laboratoryinvestigations to be performed to monitor and safeguard my body functions.


I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “Multicentric Open Clinical Trial of Selected (Dhatri Lauha) Drugs inIron Deficiency Anaemia.”

Date: _____________ Name of subject: _________________________

Signature or Thumb impression: ______________

Date: _____________ Name of witness: _________________________


Relationship: _____________________________

Translate into regional language

836





Iron Deficiency Anaemia is a worldwide problem with the highest prevalence in developingcountries. It is found especially among women of childbearing age, young children and duringpregnancy & lactation. In conventional medicine various forms of iron viz. Ferrous sulfate, ferrousfumerate etc. are commonly prescribed, but these therapies have their certain limitations.

The council has initiated scientific studies for revalidation (through measurable objectiveparameters) of certain classical formulations that are being successfully prescribed by Ayurvedic/Siddha physicians without any side effects since centuries. In scientific studies no adverse effectsare reported.

Beneficiaries and benefits

Subjects suffering from Iron Deficiency Anaemia, after free consultation and screening byphysician, if found suitable shall be provided free medicines & laboratory investigations etc. forcertain time. Consolidated amount for traveling / wage loss shall be provided to the suitableindividuals on each visit till completion of the study.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 15 days. During treatment period,you are expected to visit the hospital three times i.e. on 0th, 8th, 15th, 30th and 45th day for clinicaland physiological assessment.




Translated into regional language

837




BEFORE TREATMENT


1. Code No. (of clinical trial): 01

2. Center: ____________________

3. Subject Name__________________________________

4. Sex Male Female

5. Date of birth : Age (in years):

6. Address: Permanent postal address with phone number & E-mail if any.

_____________________________________________________________________

_____________________________________________________________________



2. Hemoglobin level between 6 to 10 gm / dl

3. Serum iron content < 50 ìg /dl

4. S. Ferritin < 30 ìg /L

5. MCHC < 34 g/dl

6. MCV<80 fl

7. Peripheral smear for blood shows

8. Hypochromic & Microcytic anaemia



10. Pregnant / lactating woman

838

11. Severe Renal/Hepatic/Cardiac disease*

12. Any continuing blood loss e.g. hematemesis,

melena and bleeding piles etc.

13. Dimorphic anaemia

14. History of Chronic Infections



If enrolled:-

Subject Sl. No.: ____________ No. of strips issued__________

Date: _______________ Signature of the Investigator: ________________Name of the Investigator: ___________________

* Normal range of values for Sl. No. 17


a). S. Bilirubin

i. Total 0.3 – 1.0 mg/dl

ii. Direct 0.1 – 0.3 mg/dl

b). SGPT 0 – 35 IU/L

c). SGOT 0 – 35 IU/L

d). S. Alkaline phosphatase 30 – 120 IU/L

e). S. Proteins (Total) 5.5 – 8.0 g/dl

i. Albumin 3.5 – 5.5 g/dl

ii. Globulin 2.0 – 3.5 g/dl


f). Blood urea 15 – 40 mg/dl

g). S. Creatinine < 1.5 mg/dl

839



CASE REPOTR FORM II – HISTORY



2. Center: ____________________

3. Sr. No. of the Subject: _______________________________

4. Subject Name: ______________________________________

5. Sex Male Female


7. Address: Permanent postal address with phone number & E-mail if any.

__________________________________________________

__________________________________________________

8. Educational status: Illiterate 1 Read and Write 2

Primary School 3 Middle School 4

High School 5 College 6


9. Annual Income of the family Rs.

10. Total number of members sharing the income:




If Field work, indicate nature of work: ________________________________________

840



Yes (1) No (0) If Yes Duration (in days)

12. Weakness

13. Fatigue

14. Palpitation

15. Effort intolerance

16. Breathlessness

17. Swollen feet

18. Asymptomatic


20. Previous episodes Yes 1 No 2


PERSONAL HISTORY:

Addictions: Yes (1) No (0)

22. Alcohol:

23. Tea / Coffee more than 4 times a day

24. Tobacco

If yes: Chewing 1 Smoking 2 Both 3

25. Diet Vegetarian 1 Non-vegetarian 2

26. Menstrual history: Regular 1 Irregular 2

If irregular, Specify___________________________________

Duration of menstruation Up to 5 days 1 5-7 days 2 More than 7 days 2

Quantity Normal 1 Abnormal 2

If abnormal, specify__________________________________

841

27. Sharirik Prakriti: Vata 1 Pitta 2 Kapha 3


Sannipataja 7

PHYSICAL EXAMINATION:



30. Body weight (Kg.) __________

31. Height (cm.)_________

32. Body temperature (oF)____________

33. Blood pressure (in sitting posture of right upper limb) –

Systolic_______mm/Hg

Diastolic _______mm/Hg




36. Pallor

37. Koilonychia

38. Lymphadenopathy

SYSTEMIC EXAMINATION:


39. CVS with chest

If Abnormal, specify abnormalities________________________________

40. CNS

If abnormal, specify abnormalities________________________________


842







Liver

Spleen




46. Anubandh dosha

47. Avraka dosha

48. Ksheena dosha

49. Ksheena dhatu: Rasa 1 Rakta 2 Mamsa 3 Meda 4

Asthi 5 Majja 6 Shukra 7 Oja 8

50. Dusya Rasa 1 Rakta 2 Mamsa 3 Meda 4

Asthi 5 Majja 6 Shukra 7 Oja 8

Date: __________________ Signature of the Investigator: ____________________

Name of the Investigator: ______________________

843



CASE REPORT FORM – III PERIODICAL OBSERVATION AND CLINICALASSESSMENT

(0th day)



2. Center: _______________________

3. Sr. No. of the Subject: ____________________________

4. Subject Name: ___________________________________

5. Sex Male 1 Female 2




Yes (1) No (0) If yes, Duration (in days)

8. Weakness

9. Fatigue

10. Palpitation


12. Breathlessness

13. Swollen feet

Yes (1) No (0)

14. Asymptomatic

15. Other Associated Symptoms

844

If yes, specify: ___________________________

___________________________

___________________________

Date: ______________ Signature of Investigator: _________________

Name of Investigator: ____________________

845




(On 15th Day)



2. Center: ____________________

3. Sr. No. of the Subject: ___________________________

4. Subject Name: __________________________________






8. Weakness

9. Fatigue

10. Palpitation


12. Breathlessness

13. Swollen feet

14. Asymptomatic


If yes, specify: ___________________________

___________________________

846

Adverse Reactions: Present (1) Absent (0) If yes, Duration (in days)


17. Nausea

18. Diarrhoea

19. Skin rashes

20. Any other adverse complaints/observations specify______________________________






Continuing 1

Drop out 2 Reason: _____________________________________________

Death 3 Cause: ______________________________________________

If continuing, No. of blisters issued: __________________________________________

Date: ______________ Signature of Investigator ____________________

Name of Investigator ______________________

847




(On 30th Day)



2. Center: _______________________

3. Sr. No. of the Subject: ____________________________

4. Subject Name: ___________________________________






8. Weakness

9. Fatigue

10. Palpitation


12. Breathlessness

13. Swollen feet

14. Asymptomatic


If yes, specify: ___________________________

___________________________

848



17. Nausea

18. Diarrhoea

19. Skin rashes

20. Any other adverse complaints/observations specify_______________________________






Continuing 1

Drop out 2 Reason: ______________________________

Death 3 Cause: _______________________________

If continuing, No. of blisters issued: __________________________


Name of Investigator ____________________

849




(On 45th Day)



2. Center: _______________________


4. Subject Name: __________________________________






8. Weakness

9. Fatigue

10. Palpitation


12. Breathlessness

13. Swollen feet

14. Asymptomatic


If yes, specify: ___________________________

___________________________

850



17. Nausea

18. Diarrhoea

19. Skin rashes

20. Any other adverse complaints/observations specify_______________________________






Completed 1

Drop out 2 Reason: _____________________________

Death 3 Cause: ______________________________


Name of Investigator ____________________

851




(0th Day)



2. Center: ____________________


4. Subject Name: __________________________________

5. Sex Male 1

Female 2



URINE EXAMINATIONRoutine


8. Sugar

9. Albumin

10. Bile Salts

11. Bile Pigments

Microscopic


12. RBC

13. Pus Cells

14. Epithelial Cells

15. Any others _________________________________________

852

STOOL EXAMINATIONRoutine


16. Occult Blood

Microscopic


17. Ova/Cyst

BLOOD

18. TC (Cells/Cu. mm.) _______________

19. DC: P ______ (%) L ______ (%) E ______ (%) M ______ (%) B ______ (%)

20. ESR (mm / 1st hour.) _________________

21. M.C.H.C. (g/dl)______________________

22. M.C.V. (fl)__________________________

23. Serum iron (ìg/dl)_____________________

24. Serum ferritin (ìg/L) ___________________

25. Hb (g/dl) (Cyanomethamoglobin method) _____________________________________

26. PCV (%) _________________

27. TIBC (μg/dl) ____________

28. General Blood Picture for morphology of RBC ______________________________

Normocytic Normochromic (1) Normocytic Hypochromic (2)

Macrocytic Normochromic (3) Macrocytic Hypochromic (4)

Microcytic Hypochromic (5)


29. Serum Bilirubin

Total (mg/dl) ________

Direct (mg/dl) _________

853

30. SGPT (IU/L) ________

31. SGOT (IU/L) ________

32. S. Alkaline phosphatase (U/L) ________

33. S. Proteins (Total) (g/dl) _____________

34. Albumin (g/dl) ________

35. Globulin (g/dl) ________


36. Blood urea (mg/dl) __________

37. S. Creatinine (mg/dl) _________

Date: _____________ Signature of the Investigator ______________

Name of the Investigator _________________

854


MULTICENTRIC OPEN CLINICAL TRIAL OF SELECTED DRUGS IN

IRON DEFICIENCY ANAEMIA.

CASE REPORT FORM IV-B – LABORATORY INVESTIGATIONS

(15th Day)



2. Center: _______________________


4. Subject Name: __________________________________




8. M.C.H.C. (g/dl)____________________

9. M.C.V. (fl)________________________

10. Serum iron (ìg/dl)___________________

11. Serum ferritin (ìg/L) _________________

12. Hb (g/dl) (Cyanomethamoglobin method) _______

13. PCV (%) _______________

14. TIBC (ìg/dl) ___________

15. General Blood Picture for morphology of RBC ____________________




Date: _____________ Signature of the investigator ___________________

Name of the investigator _______________________

855


MULTICENTRIC OPEN CLINICAL TRIAL OF SELECTED DRUGS IN

IRON DEFICIENCY ANAEMIA.

CASE REPORT FORM IV-B – LABORATORY INVESTIGATIONS

(30th Day)



2. Center: _______________________


4. Subject Name: __________________________________

5. Sex Male 1

Female 2



8. M.C.H.C. (g/dl)____________________

9. M.C.V. (fl)________________________

10. Serum iron (ìg/dl)___________________

11. Serum ferritin (ìg/L) _________________

12. Hb (g/dl) (Cyanomethamoglobin method) _______

13. PCV (%) _______________

14. TIBC (ìg/dl) ___________

15. General Blood Picture for morphology of RBC ____________________




Date: _____________ Signature of the investigator ____________________

Name of the investigator ________________________

856




(45th Day)



2. Center: ____________________


4. Subject Name: __________________________________

5. Sex Male 1

Female 2



URINE EXAMINATIONRoutine


8. Sugar

9. Albumin

10. Bile Salts

11. Bile Pigments

Microscopic


12. RBC

13. Pus Cells


15. Any others: ___________________________________

857

STOOL EXAMINATIONRoutine Absent (0) Present (1)

16. Occult Blood

Microscopic


17. Ova/Cyst

BLOOD

18. TC (Cells/Cu. mm.) _______________

19. DC: P _____ (%) L _____ (%) E _____ (%) M _____ (%) B _____ (%)

20. ESR (mm / 1st hour.) __________

21. M.C.H.C. (g/dl)________________

22. M.C.V. (fl)______________________

23. Serum iron (ìg/dl)_____________________

24. Serum ferritin (ìg/L) __________________

25. Hb (g/dl) (Cyanomethamoglobin method) ____________________

26. PCV (%) ___________

27. TIBC (μg/dl) ___________






29. Serum Bilirubin

Total (mg/dl) ________

Direct (mg/dl) _________

30. SGPT (IU/L) ________

858

31. SGOT (IU/L) ________

32. S. Alkaline phosphatase (U/L) ________

33. S. Proteins (Total) (g/dl) _____________

34. Albumin (g/dl) ________

35. Globulin (g/dl) ________


36. Blood urea (mg/dl) ________

37. S. Creatinine (mg/dl) ________

Date: _____________ Signature of the Investigator ____________________

Name of the Investigator _______________________

859



CASE RPORT FORM – V



2. Center: _______________________


4. Subject Name: __________________________________


Sl Subjective/ objective 0 day/BT 15th day 30th day 45thday/ATParameters Dt. Dt. Dt. Dt.

Yes No Yes No Yes No Yes No(1) (0) (1) (0) (1) (0) (1) (0)

1. Weakness

2. Fatigue

3. Palpitation


5. Breathlessness

6. Swollen feet

7. Other Associated Symptoms if Any [Specify]

Adverse reactions

8. Burning sensation in Not applicableabdomen

860

9. Nausea Not applicable

10. Diarrhoea Not applicable

11. Skin rashes Not applicable

12 TC (Cells/Cu. mm.)

DC (%) 13. P 13. P

14. L 14. L

15. E Not applicable Not applicable 15. E

16. M 16. M

17. B 17. B

18 ESR (mm / 1st hour.) Not applicable Not applicable

19 M.C.H.C. (g/dl)

20 M.C.V. (fl)

21 Serum iron (ìg/dl)

22 Serum ferritin (ìg/L)

23 Hb (g/dl)(Cyanomethamoglobinmethod)

24 PCV (%)

25 TIBC (ìg/dl)

26 General BloodPicture formorphology of RBC

Liver function testsS. Bilirubin

27. Total (mg/dl)28. Direct (mg/dl)

29. SGPT (IU/L)

30. SGOT (IU/L)Not applicable Not applicable

861

31. S. Alkalinephosphatase (U/L)

32. S. Proteins (Total)(g/dl)

33. Albumin (g/dl)

34. Globulin (g/dl)



36. S. Creatinine (mg/dl)

Urine Examination

Routine

37. Sugar

38. Albumin (gm/dl)

39. Bile Salts

40. Bile Pigments

Microscopic

41. RBC

42. Pus Cells


44. Any others

Stool Examination

45. Occult Blood

46. Ova/Cyst





Not applicable Not applicable





862


Completed 1

Drop out 2 Reason: ______________________________

Died 3 Cause: _______________________________

Date: ______________ Signature of the investigator _____________________

Name of the investigator: _______________________

863

Drug: Study Code:


TO EVALUATE THE SAFETY AND EFFICACY OFAYUSH-RP IN SICKLE CELL ANEMIA


864

Blank

865

I. BACKGROUND

Sickle Cell Anaemia (SCA) is a chronic hemoglobinopathy characterized by frequentepisodes of painful arises, widespread tissue infarcts causing multisystem dysfunction, chronicanaemia, increased susceptibility to infection & growth retardation (Francklin Bunn 1987). Thereare many genotypes of sickle hemoglobinopathies e.g. Sickle Cell Anaemia, Sicke Cell traint (HbStrait), S/ß0 thalassemia/Sß + thalassemia haemoglobin SC, SD, SE. The prototype of Sicklehemoglobinopathy is Sickle Cell anemia, is the homozygous state for HbS. The Sickle Cell Anemiais caused by a mutation in the ß-globin gm that changes the sixth amino acid from Glutamic acidto valine HbS ß

2ß

26Glu’→Val). Hypoxia, pyrexia & acidosis aggravate sickling. The precipitating

cause is not always detectable. The Clinical features of Sickle Cell disorder have got maximumresemblance with Raktadusti, Jeernajwara, hepatomegaly, splenomegaly) rather than PanduRoga as described in Compendiums of Ayurvedic System of Medicine. A variety of drugs likeurea, zinc, cyanate, vitamin-E, magnesium sulphate, cietidil, 5 azamutidine, hyperbolic oxygen andpentoxifyline, etc. have all produced equivocal results. Recently antibiotic prophylaxis withsplenectomised patient, vigorous hydration with narcotic analgesic. Exchange blood transfusion,hydroxurea, S-Arginine, folic acid supplements, clotirimazole are the mainstay of treatment butrecent treatment proved to be expensive & toxic side effect (Bone marrow toxicity ofhydroxyurea). Bone marrow transplantation is most effective treatment in modern medicines but itis too expensive. Therefore, this study aims to evaluate the effect of Ayurvedic drug which has lowcost, probably low toxicity and probably that lessons the sickle cell crises.

II. AIM & OBJECTIVES

The objectives will be to evaluate the changes in frequency of Sickle Cell crisis withAYUSH-RP in Sickle Cell Anaemia.


TO EVALUATE THE SAFETY AND EFFICACY OF AYUSH-RP IN SICKLECELL ANAEMIA

References

1. API, Textbook of Medicine 5th Edition Reprint 1994 P.997-998

2. Davidson’s Principle and Practice of Medicine 19th Edition p.926-927

3. Harrison’s is Principle of Internal Medicine 15th Edition 669-671

4. Hemoglobin level and prevention of repeated Blood transfusion in sickle cell disorders withclassical Ayurvedic formulation, R.K.Panda. JRAS XVII, 47-55.

866

III. CENTRES -



Sample size: 20 subjects per centre.

Drug:

(i) Drug/Dosage/Duration: Ayush-RP 500 2 cap. BID with lukewarm water for sixmonths before food for six months.

(ii) Design of the study - Open trial (Pilot study)

Duration of the study – 6 months with drug and without follow up for another sixmonths.

Total period of the study - 2 years. (Recruitment for nine months. Treatment and followup for one year and three months for statistical analysis).


1. Age >5 years with or without fever, muscular pain in both extremities & Hepatomegaly.

2. Patients having hemoglobin > 5 gm%.

3. Diagnosed Patients on the basis of peripheral smear for sickling & HaemoglobinElectrophoresis.


4. Patient with Hb% < 5 gm%.

5. Patient with end stage renal disease.

6. Patient with documented infection.

7. Severe liver dysfunction.

8. Patient with acute chest syndrome (Like Respiratory failure, pulmonary edema/ embolism/infarction.

9. Patient on bone marrow transplant/renal transplant.


During the course of trial if any serious condition (Liver, kidney and lungs functiondeteriorates) develops which requires urgent treatment such subject may be withdrawn from trial& managed by principle investigator accordingly.

867


The full details of history and physical examination of the patients will be recorded as perthe proforma (Forms I & IA). Clinical assessment will be done before drug administration, at thestart of the treatment and then monthly during treatment period and follow up period for 6 month.The laboratory investigations will be recorded before drug administration, at the start of treatmentthen monthly during treatment period and follow up.

IX. CRITERIA FOR ASSESSMENT OF RESULT OF TREATMENT

METHOD OF ASSESSMENT:

Two parameters subjective and objective were used for assessment of progress:

i. SUBJECTIVE PARAMETERS: The symptoms e.g. fever, weakness, abdominaldiscomfort & pain in extremities observed during the follow up period were grades0,1,2,3 on the basis of severity and duration. The improvement was confirmed fromfavourable shift grade of each sign & symptoms from grade 3-0 as follows.

SUBJECTIVE SYMPTOMS GRADES

Fever 0,1,2,3

Weakness 0,1,2,3

Abdominal discomfort 0,1,2,3

Pain in the extremities 0,1,2,3

ii. OBJECTIVE PARAMETERS:

i. Increase level of Haemoglobin.

ii. Change of size of liver and spleen.

iii. Changes of frequency of crisis.

XI. STATISTICAL ANALYSIS:

On the basis of above mentioned subjective and objective parameters result will beanalyzed using appropriate statistical parameters.

XII. TRIAL MONITORING AND DATA ANALYSIS:

The progress of the trial will be monitored by field visits by Monitoring Unit and Staff ofcollaborating agencies (Department of ISM&H and ICMR, Hqrs, New Delhi.) regularly.

Data analysis will be undertaken at the Monitoring Unit/Department of ISM & H.

868

XIII. ETHICAL REVIEW:



869


TO EVALUATE THE SAFETY AND EFFICACY OF AYUSH-RP IN SICKLECELL ANEMIA

CONSENT FORM




Name: ____________________________

CONSENT BY SUBJECT

I have been informed to my satisfaction, by the attending Physician, the purpose of theclinical trial and the nature of drug treatment and follow-up, including the laboratory investigationsto be performed to monitor and safeguard my body functions.


I, exercising my free power of choice, herby give my consent to be included as a subjectin the clinical trial of Ayurvedic drug in Sickle Cell Anaemia.





Relationship ___________________________________


870


PROTOCOL TO EVALUATE THE EFFECT OF AYURVEDIC DRUG IN SICKLECELL ANAEMIA



Sickle Cell Anaemia (SCA) is a chronic hemoglobinopathy characterized by frequentepisodes of painful crisis, widespread tissue infarcts causing multisystem dysfunction, chronicanemia increased susceptibility to infection and growth retardation. It is caused by mutation in theB-globin of haemoglobin. In Indian, it is more prevalent in tribal area of Orissa, Madhya Pradesh,Maharashtra. It occurs in both sexes occurrence at the ages of 3 to 30 yrs. There are variousmodern drug available but recent treatment proves to be expensive and have toxic side effects.Therefore, this study aims to evaluate the safety & efficacy of Ayurvedic drug in Sickle CellAnaemia which has low cost & probably low toxicity (the symptoms of gastrointestinal tract e.g.Nausea, vomiting, diarrhoea, any abdominal discomfort if any).


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take 6 month treatment period. During this period youhave to visit at beginning of treatment and monthly during treatment period and follow up forclinical assessment and Lab. Investigation.

Before you start of treatment clinical assessment and the biochemical test will be carriedout. If your diagnosis is confirmed and you will be a fit case you will be subjected to this studyfor the period of one year you will be supplied with the sufficient quantity of medicine to last untilyour next visit and once in every months the clinical assessment and blood test will be repeated toassess therapeutic efficacy of drug.


871


PROTOCOL TO EVALUATE THE EFFECT OF AYURVEDIC DRUG IN SICKLECELL ANAEMIA

CASE REPORT FORM PART-I – SCREENING

1. Centre: ………………..……….


3. Patient No.

4. Name of the patient: ………………………………........ Age .................. Sex .................

5. Address : ..............................................................................................................................

CRITERIA FOR INCLUSION

6. Age >5 years with or without fever, muscular pain in both extremities & Hepatomegaly.

7. Patients having haemoglobin >5 gm%.

8. Diagnosed Patients on the basis of peripheral smear for sickling & Haemoglobin Electrophoresis.

CRITERIA FOR EXCLUSION

9. Patient with Hb% < 5 gm%

10. Patient with End stage renal disease.

11. Patient with documented infection.

12. Severe liver dysfunction

13. Patient with acute chest syndrome (Like Respiratory failure, pulmonary edema/ embolism/infarction.

12. Patient on bone marrow transplant/renal transplant

If yes to 4-6 & no to 7-12, then patient should be included into the study.

872


PROTOCOL FOR TO EVALUATE THE EFFECT OF AYURVEDIC DRUG INSICKLE CELL ANAEMIA

CASE REPORT FORM PART-II HISTORY PROFORMA

1. Centre: ………………..……….


3. Patient No.

4. Name of the patient: ………………………………........ Age .................. Sex .................

5. Address : ..............................................................................................................................

6. Date of admission: Date of Discharge :









9. Total income of the family in rupees


11. Religion: Hindu Muslim Sikh

Christian Parsi

12. Marital status: Married Unmarried Divorcee/separated

873

Chief Complaints with Duration (in days) Present Absent Duration

13. Fever

14. Weakness

15. Pain in hip and shoulder joints.

16. Any other joint pains.

17. Pain in extremitiesback, hand, foot, muscle

18. Abdominal discomfort

19. Yellowish Eye, yellow colour urine

20. Any altered sensation in the limbs

21. Chest pain (pleuritic)

22. Any rash

23. Priapism

24. Any C/o growth retardation.

25. Any vision disturbances

26. Any other complaints specify.


Past history of illness: History of bleeding from the nose and history of conversion, giddinessfainting, attack, CVA, if any


28. Previous episodes Yes No

29. Type of fever-periodicity 24 hrs. 48 hrs.


874

31. Treatment given so far Ayurvedic medicine Modern medicine

Unani Homoeopathy

Siddha Mixed

Spell out the medicine and results obtained

______________________________________________________________________________________________________________________________________________

Personal History :

Yes No

32. Smoking

33. Obesity

34. Non-Vegetarian

35. Alocholic

36. Prakriti

Vataj Pittaj Kaphaj

Vataja-Kaphaja Vataj-Pittaja Pittaja-Kaphaja

Sannipataja

37. Manas Prakriti

Sattava Rajas Tamas

Sattava-Rajas Rajas-Tamas Sattva-Tamas

Sama




40. Body weight (in Kgs.)

875

41. Body temerature :

42. Blood pressure (Systolic/Diastolic)

43. Pulse

44. Respiration

Present Absent

45. Cynosis

46. Anaemia

47. Jaundice

48. Pigmentation


50. Ulcer

51. Lymphadenopathy

52. Rash/erythema, pallor


Normal Abnormal

53. C.V.S. with chest

If abnormal, specify abnormalities : ......................................................................................

54. C.N.S.






876{}


If abnormal, specify abnormalities: _________________________________

58. Liver Palpable Not palpable

Size in cm.

59. Spleen Palpable Not palpable

Size in cm.

Present Absent

60. Tumour/Lump

61. Portal ascites

SAMPRAPTI (PATHOGENESIS) OF THE DISEASE ACCORDING TO AYURVEDICCONCEPT

Vata Pitta Kapha


63. Anubandh dosha

Avrak dosha

Ksheen dosha

Ksheen dhatu Rasa Rakta Mamsa

Meda Asthi Majja

Shukra Oja

Dusya Rasa Rakta Mamsa

Meda Asthi Majja

Shukra

877



Sthansamshraya Vyakti Bheda

65. Srotas Pareeksha

Pranvaha Srotas

Alpa Alpa Swasa (Shortened breathing)

Atisrama Swasa (Increased respiration rate)

Abhiksham Swasa (Chyne stroke breathing)

Kupit Swasa (Vitiated breathing)

Sashula Swasa (Dyspnoea with pain)

878



CASE REPORT FORM III – CLINICAL & PHYSIOLOGICAL ASSESSMENT

(Monthly during treatment period and follow up)

1. Centre: ………………..……….


3. Sr. No. of the Subject: ……………………………........…………………………………




Clinical Symptoms Absent Present

7. Relief in fever

8. Weakness

9. Abdominal discomfort

10. Pain in extremities

11. Pain in hip and shoulder joints

12. Any other joint pains

13. Other complaints, if any (Specify)_____________________________________________


If yes, Present specify _____________________________________________________

15. Frequency of crisis

16. Adverse reaction: No (0) Yes (1)

If yes, details: ___________________________________________________________

879




Continuing (1)

Drop out (2) Reason: _____________________________

Died (3) Cause: _______________________________

19. Systolic blood pressure (mm of Hg) __________________________________________

20. Diastolic blood pressure (mm of Hg) _________________________________________

21. Weight (kg) _____________________________________________________________

Date: ____________ Signature of the Investigator:________________

880



(Monthly during treatment and monthly during follow up)


(To be done before, at the end of three months and end of the treatment)

1. Centre: ………………..……….


3. Sr. No. of the Subject: ……………………………........…………………………………






8. TC (Cells/Cmm.) __________________________

9. DC: P (%)_______ L (%)_______ E (%)_______ M (%)_______ B (%)_______

10. Hb(g/dl) _________.

11. PCV (%) ___________

12. ESR (1st hour) (mm) _____________________

13. BT

14. CT

15. Platelet count

16. Reticulocyte count

881

17. Peripheral smear for sickling (before treatment only)

18. Serum Iron (Microgram per dl.)

19. Serum Ferritin (Nanogram/ml.)

20. Sickling test (before and end of the treatment only)

21. Haemoglobin Electrophoresis (before treatment only)

22. Serum Hb. F level (0 and 6 months)

Serum Hb. S level (0 and 6 months)

23. B. Urea (mg./dl) ________________

24. S. Creatinine (mg./dl) ________________


25. S. Bilirubin

26. SGPT

27. SGOT

28. S. Alkaline phosphates

29. S. Proteins

882

Blank

IMMUNE SYSTEM

SEC

TIO

N - X

V

884

Blank

885

EVALUATION OF EFFICACY OF AYUSH-QOL-2 INHIV INFECTED PERSONS AS AN SUPPORTIVE

THERAPY

Drug: Study Code:



886

Blank

887


EVALUATION OF EFFICACY OF AYUSH-QOL-2 IN HIV INFECTEDPERSONS AS AN SUPPORTIVE THERAPY

I. BACKGROUND

Acquired immunodeficiency Syndrome1 or AIDS is a disease of the defense system of thebody. The causative organism is Human Immunodeficiency Virus (HIV), which belongs to thefamily of human retroviruses. This virus attacks the immune system of the human beings, leadingto depletion of CD4 cells resulting in immunodeficiency. Because of immunodeficiency the personbecomes susceptible to various secondary infections and neoplasm that are AIDS-definiting illness.

The World Health Organisation estimates that there are over 1.75 millions HIV infectedadults throughout India. In majority of cases infection occur through sexual route and rest throughblood transfusion, injecting drugs etc.

There are four broad approaches to the treatment of HIV infection. These include 1.Treatment or prophylaxis of specific opportunistic infections 2. General management 3. Antiretroviral agents, which include reverse transcriptase (RT) inhibitors and proteinase inhibitors 4.Immunorestorative therapy.

Presently Zidovadine (AZT), Didanosine, Zalcitabine and Lamivudine are available RT-inhibitors; Saquinavir, Kitovavir and Indinovir are the available proteinase inhibitors.

However, the major limitations of these drugs to be used in our country include 1.Restricted availability in our country. 2. Major side effect 3. High cost 4. Unequivocal findings intheir role in preventing progression to AIDS related complex (ARC) or AIDS.

WHO had noticed inability of people in developing countries to purchase costly medicinesused in the treatment of AIDS. Hence it is trying to promote indigenous drugs available in thesecountries, through scientific study.

Since the initial recognisition of the clinical manifestations of HIV-1 infection are the resultof declining cellular and humoral immune responsiveness, there have been a number of efforts toreverse this decline through the use of a) agents with putative general immune enhancing activityand b) recombinant cytokines. However, these are complicate both by uncertainty of mechanismin terms of agents with putative general immune enhancing activity and by the complex immuneregulatory milieu in which either general immune modulators or cytokines are used.

Immune based therapeutic intervention for HIV-1 infection may be divided into two broadcategories. These include reconstitution of general immune responsiveness and augmenting HIV-1 specific immune responses.

1. Harrison’s Principle of Internal medicine: 15th Edition

888

The development of highly active antiretroviral drugs, especially protease inhibitors, hasresulted in the identification of potent combination regimens that clearly serve as the main stay ofcurrent therapy for HIV infection. However, despite the profound suppression of viral replicationthat can be seen with these combination therapies, the level of immune restoration associated withsuch therapies appear to be limited in many patients. Furthermore, the duration of viral suppressionin many patients is also limited, especially for those with long exposure histories to many of theavailable antiretroviral drugs, which were often utilized sequentially as single agents. Thusidentification of effective alternative therapeutic approaches for the treatment of HIV-infectedpatients is essential.

Some studies showed that Ayurvedic preparations were effective only if used asprophylactic and not if used as curative. They produce most of their effects by primarily acting onthe immune system. It had been shown that Ayurvedic preparations, given to rats whosemacrophages have been overloaded with a fat lipofyundin, were unable to stimulate macrophagesand thus proving that stress induced damage is no preventable.

Ayurvedic preparations act primarily by activating the macrophages. It increases thephagocytic activity of macrophages and also induces expression of MHC-II antigens indicatingenhancement of their antigen-presenting ability. In vitro, treatment of mice splenocytes withAyurvedic preparations stimulated the production of II-2, IFN-Gamma and TNF-Alpha reflectingactivation of Th-1 type of T cell responses. Since Th-1 type of response has been implicated withthe cell mediated immunity the therapeutic effect of Ayurvedic preparation, as reported may bemediated by activation of cellular immune responses. In fact, the antimicrobial properties ofAyurvedic preparation have found to be mediated by the immune system.

In the Indian scenario, Ayurveda could possibly contribute in this respect by using rasayanaand balya oushadi dravyas. The development of immune-potentiators with Ayurvedic drugs hasopened an entirely new chapter in therapeutics.

In AIDS the patient losses something essential. The cellular immunity becomes defenselessagainst the pathogens and suffers from various clinical manifestations. These manifestations aresimilar to that of OJOKSHAYA2-3 or BALAKSHAYA patients, depicted in Ayurvedic classics.By administrating the rasayana medicaments meant for ojovardhaka, balavardhaka which willpromote the process of dhatu poshana and enrich ojus and thus leads to improve the vitalstrength and immunity or vyadhi kshamatva (non-specific immunity).

2. Charaka Samhita, Sutra Sthana Chapter – 17/73, Vidyotini Hindi Vyakhya by Vd. Ambikadatta

Shastry, Choukhamba Orientalia, Varanasi

3. Ambika Dutta Sashtri (1989) Susruta Samhita (text with Hindi commentary), Sutra Sthana, Chapter15/24, VIIth, Edition Chaukhamba Sanskrit Series Office, Varanasi.

889

If AIDS is treated in this way, it may lead to break through for newer views in solving theproblem.

Hence the present study is designed to evaluate efficiency of certain selected Ayurvedicformulations in HIV/AIDS patients as a supportive therapy for improving quality of life. Theselected drug will be evaluated for its rasayana and balya properties.

II. OBJECTIVE

The study is aimed to evaluate the efficacy of the Ayush-QOL-2 in HIV infected persons,as a supportive therapy for the improvement of quality of life.

III. CENTRES



Sample size : 100 subjects (divided in to two equal groups) per centre

Group I : Available standard management + Ayush – QOL –2 (considered as trailgroup) – 50 subjects

Group-II : Available standard management for HIV/AIDS patients+ Placebo(placebo/control drug will be made similar to trial drug) - 50 subjects

Dose of the trial drug : 2 tablets (500 mg/tab) tid

Type of study : Double blind randomized controlled trial.

Level of study : OPD level only.

Period of study : Six months.

Follow-up :

A. During study, patients will be screened for HIV/AIDS depending upon the investigationsreport and other clinical signs and symptoms. ELISA will be used for screening and western blottest for confirming of HIV infections. Patients will be followed for a period of six months andwere carried out investigations CD4+, Beta-2 micro globulin level, Viral load and gm% ofHaemoglobin with interval of two months.

B. In addition to laboratory findings, change in body weight, reduction in opportunisticinfections, improvement in Karnofsky performance score and improvement in clinical status of thepatient will be reviewed periodically.

890

V. CRITERIA FOR INCLUSION:

1. Age group – 20 to 60 irrespective of sex

2. Seropositive to HIV-1 or HIV-2 or both

3. Western Blot positive

4. CD4 count ranging from 200-500/cu. mm

5. Hb gm% at least 7 gm%

6. Patients with normal hepatic and renal function

7. Patients with total lymphocyte count 2000/cu.mm and platelet counts 75000/cu.mm8. Able to understand and give written consent

VI. CRITERIA FOR EXCLUSION:

1. Pregnant or lactating females.

2. Presence of serious systemic illness – e.g. Chronic renal failure, hepatic failure,cardiovascular diseases, endocrinal or metabolic disorders (such as diabetesmellitus).

3. History suggestive of pulmonary tuberculosis, pneumocystis, carinii pneumonia,toxoplasmosis.

4. Patients suffering from secondary infections or opportunistic infections like severechronic diarrhoea, all types of pneumonias, disseminated diseases, brain abcesses,meningitis, encephalitis, herpes simplex, herpes zoster, syphilis, toxoplasmosis,cytomegalovirus infection.

5. Patients with neoplasms – visceral kaposi’s, lymphomas, invasive cervicalcarcinoma.

6. Other conditions like peripheral neuropathies, pancreatitis, G6PD deficiency, HIVwasting syndrome etc. that may potentially interfere with the study.

7. Past history of drug allergies.


A patient may be withdrawn from the study in case of any one of the following

• Development/occurrence of a life threatening illness.

891

• Severe adverse effect of the drug.

VIII. ROUTINE EXAMINATION AND ASSESSMENT:

The efficacy of the trial drug will be assessed on the basis of changes in clinical parametersas well as laboratory investigations.

A. Clinical parameters:

i. Weight gain

ii. Improvement of Karnofsky performance score

iii. Reduction in opportunistic infections

iv. Improvement in clinical status of the patient (subjective scales of measurement ofsymptomatic improvement 0=Static; 1=Mildly better; 2=Moderately better;3=Much better)

B. Laboratory investigations:

i. Increase in CD4 count

ii. Decrease in Beta-2 micro globulin level

iii. Decrease in viral load

iv. Increase in Hb%

IX. GENERAL MANAGEMENT:

Patients will be managed on OPD level only at HIV/AIDS clinic, J.J. Hospital, Mumbai.Physicians on the set proforma will make periodic assessments.

Patients will be instructed to avoid other forms of medicines during the period of trial.They should report to the physicians immediately for appropriate treatment in the event ofdevelopment of other diseases.

Strict confidentiality of all data collected will be maintained to prevent embarrassment ofvictimization of patients. Consent form will be obtained from every patient.


Before treatment and after treatment data on clinical and laboratory parameters taken intoaccount for diagnosis and for the assessment of results of treatment will be tabulated and analysed

892

using suitable statistical method.


The monitoring of progress of the trial and data analysis will be undertaken by CCRAS.

XII. ETHICAL REVIEW

Each Institutional Ethical Committee (IEC) of participating Centre’s should give clearancecertificate before the project is initiated. Patient’s information sheet and informed consent formshould be submitted alongwith project proposal for approval by IEC. Both should be maintainedin duplicate with one copy given to the patient at the time of entry to the trial.

893

APPENDIX

KARNOFSKY PERFORMANCE SCORE REFERENCE SHEET

Able to carry on normal activity; No special care is needed

100 Normal; No complications; No evidence of disease.

90 Able to carry on normal activity.

80 Normal activity with effort; Some signs (or) symptoms of disease.

Unable to work; Able to live at home; Care for most personal needs; A varying amount ofassistance is needed

70 Cares for self; Unable to carry on normal activity (or) to do active work.

60 Requires occasional assistance and frequent medical care

50 Requires considerable assistance and frequent medical care.

Unable to care for self; requires equivalent of institutional or hospital care; Disease may beprogressing rapidly

40 Disabled; Requires special care and assistance.

30 Severely disabled, hospitalization is indicated, though death is not imminent.

20 Very sick; Hospitalization is necessary; Active supportive treatment is necessary.

10 Moribund; Fatal processes are progressing rapidly.

0 Dead

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Date:___________ Signature _________________________

Name ____________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included asa subject in the clinical trial on “Evaluation of Efficacy of Ayush QOL-2 in HIV InfectedPersons as an Supportive Therapy”

Date: ________________ Signature or Thumb impression_________

Name of subject____________________

Date: ________________ Name of witness: ___________________

Signature or Thumb impression: ________

Relationship: _______________________


895





Acquired immunodeficiency Syndrome or AIDS is a disease of the defense system of thebody. The causative organism is human immunodeficiency virus (HIV), which belongs to thefamily of human retroviruses. This virus attacks the immune system of the human beings, leadingto depletion of CD4 cells resulting in immunodeficiency. Because of immunodeficiency the personbecomes susceptible to various secondary infections and neoplasm that are AIDS-definiting illness.

The World Health Organisation estimates that there are over 1.75 millions HIV infectedadults throughout India. In majority of cases infection occur through sexual route and rest throughblood transfusion, injecting drugs etc.

There are four broad approaches to the treatment of HIV infection. These include 1.Treatment or prophylaxis of specific opportunistic infections 2 General management 3. Antiretroviral agents, which include reverse transcriptase (RT) inhibitors and proteinase inhibitors 4.Immunorestorative therapy.

Presently Zidovadine (AZT), Didanosine, Zalcitabine and Lamivudine are available RT-inhibitors; Saquinavir, Kitovavir and Indinovir are the available proteinase inhibitors.

However, the major limitations of these drugs to be used in our country include 1.Restricted availability in our country. 2. Major side effect 3. High cost 4. Unequivocal findings intheir role in preventing progression to AIDS related complex (ARC) or AIDS.

WHO had noticed inability of people in developing countries to purchase costly medicinesused in the treatment of AIDS. Hence it is trying to promote indigenous drugs available in thesecountries, through scientific study.

Since the initial reorganization of the clinical manifestations of HIV-1 infection are the resultof declining cellular and humoral immune responsiveness, there have been a number of efforts toreverse this decline through the use of a) agents with putative general immune enhancing activityand b) recombinant cytokines. However, these are complicating both by uncertainty of mechanismin terms of agents with putative general immune enhancing activity and by the complex immuneregulatory milieu in which either general immune modulators or cytokines are used.

Immune based therapeutic intervention for HIV-1 infection may be divided into two broad

896

categories. These include reconstitution of general immune responsiveness and augmenting HIV-1 specific immune responses.

The development of highly active antiretroviral drugs, especially protease inhibitors, hasresulted in the identification of potent combination regimens that clearly serve as the main stay ofcurrent therapy for HIV infection. However, despite the profound suppression of viral replicationthat can be seen with these combination therapies, the level of immune restoration associated withsuch therapies appear to be limited in many patients. Furthermore, the duration of viral suppressionin many patients is also limited, especially for those with long exposure histories to many of theavailable antiretroviral drugs, which were often utilized sequentially as single agents. Thusidentification of effective alternative therapeutic approaches for the treatment of HIV-infectedpatients is essential.

Some studies showed that Ayurvedic preparations were effective only if used asprophylactic and not if used as curative. They produce most of their effects by primarily acting onthe immune system. It had been shown that Ayurvedic preparations, given to rats whosemacrophages have been overloaded with a fat lipofyundin, were unable to stimulate macrophagesand thus proving that stress induced damage is no preventable.

Ayurvedic preparations act primarily by activating the macrophages. It increases thephagocytic activity of macrophages and also induces expression of MHC-II antigens indicatingenhancement of their antigen-presenting ability. In vitro, treatment of mice splenocytes withAyurvedic preparations stimulated the production of II-2, IFN-Gamma and TNF-Alpha reflectingactivation of Th-1 type of T cell responses. Since Th-1 type of response has been implicated withthe cell mediated immunity the therapeutic effect of Ayurvedic preparation, as reported may bemediated by activation of cellular immune responses. In fact, the antimicrobial properties ofAyurvedic preparation have found to be mediated by the immune system.

In the Indian scenario, Ayurveda could possibly contribute in this respect by using rasayanaand balya oushadi dravyas. The development of immune-potentiators with Ayurvedic drugs hasopened an entirely new chapter in therapeutics.

In AIDS the patient losses something essential. The cellular immunity becomes defenselessagainst the pathogens and suffers from various clinical manifestations. These manifestations aresimilar to that of OJOKSHAYA - or BALAKSHAYA patients, depicted in Ayurvedic classics.By administrating the rasayana medicaments meant for ojovardhaka, balavardhaka which willpromote the process of dhatu poshana and enrich ojus and thus leads to improve the vitalstrength and immunity or vyadhi kshamatva (non-specific immunity). If AIDS is treated in thisway, it may lead to break through for newer views in solving the problem.

897


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 180 days. During treatment period,you are expected to visit the hospital in 30 days interval for clinical and physiological assessment.



At each visit, you will be supplied with sufficient quantities of drugs to last untilyour next visit. If any adverse reactions like skin allergy, nausea, vomiting andpalpitation/tremor etc., noticed during the treatment period, this should be noticed to thePrincipal Investigator.


898


EVALUATION OF EFFICACY OF AYUSH-QOL-2 IN HIV/AIDS PATIENTSCASE REPORT FORM -I SCREENING


2. Centre _______________________________________

3. Name of the patient_______________________________________________________


5. Date of Birth: Age (in yrs.)

6. Address: ______________________________________________________________

CRITERIA FOR INCLUSION

Yes (1) No (0)

1. Age group – 20 to 60 irrespective

2. Seropositive to HIV-1 or HIV-2 or both

3. Western Blot positive

4. CD4 count ranging from 200-500/cu.mm

5. Hb gm% at least 7 gm%

6. Patients with normal hepatic and renal function

7. Patients with total lymphocyte count 2000/cu.mm

8. Platelet counts 75000/cu.mm

CRITERIA FOR EXCLUSION

Yes (1) No (0)

9. Pregnant or lactating females

10. Presence of serious systemic illness

11. History suggestive of pulmonary tuberculosis,

899

pneumocystis, carinii pneumonia, toxoplasmosis.

12. Patients suffering from secondary infections or

opportunistic infections

13. Patients with neoplasms

14. Peripheral neuropathies, pancreatitis, G6PD

deficiency, HIV wasting syndrome etc.

15. Past history of drug allergies.



If admitted:

Sr. No. of the Subject: _______________

Group: Control Trial

No. of packets issued:

Date: ______________ Signature of the Investigator_______________

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CASE REPORT FORM-II HISTORY



2. Centre __________________________________

3. Sl. No. of the subject: ___________________________________________________



6. Address: _______________________________________________________________

7. Educational Status

Illiterate 1 Read and Write 2 Primary School 3






Indicate nature of work: . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . .

9. Income per capita per month in Rs


11. Marital Status: Married 1 Unmarried 2 Widow 3


In case of (3), (4) or (5) since when ________________________________________

12. Sexual History Heterosexual 1 Homosexual 2

Bisexual 3 Multi partner 4

Abstentation 5

901

13. History of exposure towardsmedical causes

1. Blood transfusion

2. Blood products

3. Major surgery

4. I.V drug use

5. Needle pricks/Needle stick injury

6. Other relevant causes

14. History of present illness: _____________________________________________

_____________________________________________

_____________________________________________

15. History of past illness: _____________________________________________

_____________________________________________

_____________________________________________

16. Family History _____________________________________________

_____________________________________________

_____________________________________________

17. Personal History

No (0) Yes (1)

1. Active drug abuse

2. Consumption of alcohol

3. Smoking habit

PlaceMonth/yearLatest episode

Yes(1)

No. of

times

No(0)

If yes

902

18. Examination of the Patient

A. General Examination No (0) Yes (1) If yes, duration(in months)

1. Fatigue

2. Fever

3. Night sweats

4. Anorexia

5. Weight loss

6. Diarrhoea

7. Cough

8. Breathlessness

9. Headache

10.Vomiting

11.Oedema

12.Dermatitis

13.Herpes

14.Any others

B. Systemic Examination Normal Abnormal


If abnormal, give the details: _________________________________________



3. Gastro-Intestinal system


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5. Genito-Urinary system

If abnormal, give the details: __________________________________________

C. Vital Signs: Present Absent

1. Pallor

2. Icterus

3. Cyanosis

Central/Peripheral)

4. Clubbing

5. Koilonychia

6. Oedema

a. Legs

b. Face

c. General

7. Lymphadenopathy

If present, size (cm)____________________

Site: Cervical____________ Axillary____________ Inguinal_______________

8. Temperature (0F):_________________

9. Pulse (rate/min.):_________________

10. Blood Pressure (Systolic/Diastolic) in mm of Hg: ____________________________

D. Anthropometry:

1. Height (in cm): _______________

2. Weight (in Kg): _______________

904

3. Chest circumference (in cm): _______________

4. Abdominal circumference (in cm): _______________

5. Mid arm circumference (in cm): _______________

6. Thigh circumference (in cm): _______________

19. Past Drug Schedule

Duration(in days)

S.No. Name of medication Period oftreatment

Prescribed by Total daily

From To Dose Unit

1.

2.

3.

4.

5.

6.

7.

8.

20. Past Adverse Drug Effects

S.No. Name of Drug Details of Adverse Effects Definite/Possible

1.

2.

3.

4.

5.

6.

7.

8.

Date: ____________ Signature of the Investigator: ____________________

905



CASE REPORT FORM-III LABORATORY INVESTIGATIONS

(All investigations to be carried out during pre-entry screening level. During treatment CD4count, Beta-2 micro globulin level, Viral load and gm% of haemoglobin will be done at every

two months interval)

General Information


2. Centre _____________________

3. Sl. No. of the subject:



6. Date of Birth: Age (in yrs):

7. Date of starting treatment:

8. Date of assessment: Month No:

Blood Tests

Negative (0) Positive (1)

9. HIV Antibodies by ELISA test

10. Western Blot test

11. Beta-2 micro globulin:____________________________________________________

12. HIV RNA Quantification (Viral load) :________________________________________

Cell Count Normal range

13. Haemoglobin : ________________ 12-16 gm/dl

14. RBC counts : ________________ 4-6 x 103/¼L

15. PCV : ________________ 37-52%

906

16. ESR (1 hour) : ________________ 10-20 mm

17. Leucocyte count : ________________ 4,000-10,000/¼L

18. Neutrophil count : ________________ 40-60%

Lymphocyte Count

19. Total T-Lymphocyte count : ________________ 60-88%

20. Total CD4 count : ________________ 32-66%

21. Total CD8 count : ________________ 10-43%

22. CD4 : CD8 ratio : ________________ 1

23. Platelet count : ________________ 150,000-400,000/¼L

Blood Chemistry + Serology

24. Anti HCV Negative (0) Positive(1) (titre:____________)

25. HBsAg Negative (0) Positive(1) (titre:____________)

26. Blood sugar (mg%) (Fasting) : ________________ 60-100 mg/100 ml

27. Blood urea (mg%) : ________________ 15-40 mg/ 100 ml

28. Serum Creatinine (mg%) : ________________ 0.5-1.5 mg/100 ml

29. Serum Uric acid (mg%) : ________________ 2.0-6.0 mg/100 ml

30. Serum Bilirubin (mg%) : ________________ 0.1-1.2 mg/100 ml

31. SGOT (IU/L) : ________________ 0 - 35 IU/ml

32. SGPT (IU/L) : ________________ 0 - 35 IU/ml

33. Total protein : ________________ 5.5 - 8.5 gm/dl

34. Albumin : ________________ 3.5 - 5.5 gm/dl

35. Globulin : ________________ 2.0 - 3.5 gm/dl

36. Prothrombin time (sec.) : Normal 11-14_________(Control)________(Patient)

907

Skin Sensitivity Test (With 5 units)

37. Mantoux test (mm) : ________________ Normal 10 mm

38. Urine

Routine _______________________________________________________________

Microscopic___________________________________________________________

39. Stool Examination

Routine ________________________________________________________________

Microscopic___________________________________________________________

40. Chest X-ray : _________________________________________________________

41. ECG : _________________________________________________________

Final Diagnosis

42. CDC STAGE: Stage II (2) Stage III (3)

Stage IV (4)

43. Sr.No. ________________________________________________________________

44. Group: Control Trial

Date:________________ Signature of Investigator: _______________________

908



CASE REPORT FORM-IV ASSESSMENT


2. Centre _____________________

3. Sl. No. of the subject:

4. Name of the patient______________________________________________________


6. Date of Birth: Age (in yrs):

7. Clinical Parameters

Clinical (Parameters) Before the trial Follow-up period (in months)

i. Weight 0 1 2 3 4 5 6

ii. Karnofsky (Performance) score

iii. Incidences of opportunistic infections

iv. Clinical status of the patient

1. Fatigue

2. Fever

3. Night sweats

4. Anorexia

5. Diarrhoea

6. Cough

7. Breathlessness

8. Headache

9. Vomitting

10. Oedema

909

11. Dermatitis

12. Herpes

13. Any others

8. Laboratory Parameters

Laboratory Parameters Before the trial Follow-up period (in months)

0 2 4 6

v. CD4 Count

vi. Bet-2 micro globulin level

vii. Viral load

viii. Haemoglobin (gm%)

9. Sr.No. of the subject: _________________________

10. Group Control Trial

11. Was the patient withdrawn from the trial? No (0) Yes (1)

If yes, principal investigator to record all details below)

12. Remarks, if any: ___________________________________________________

___________________________________________________

___________________________________________________

Date: _____________ Signature of the Investigator: ____________________

910

Blank

DISORDERS OF SKIN

SEC

TIO

N - X

VI

912

Blank

913

EVALUATION OF THE THERAPEUTIC EFFECT OFSINGLE DRUGS/COMPOUND AYURVEDIC

FORMULATIONS AND SHODHANA THERAPY IN THEMANAGEMENT OF KITIBHA (PSORIASIS)

Drug: Study Code:



914

Blank

915


EVALUATION OF THE THERAPEUTIC EFFECT OF SINGLE DRUGS/COMPOUND AYURVEDIC FORMULATIONS AND SHODHANA THERAPY IN

THE MANAGEMENT OF KITIBHA (PSORIASIS)

I. BACKGROUND:

Psoriasis1 is a common chronic non-infectious skin disease said to be idiopathic, accordingto modern medicine. In Ayurveda the causative factors of skin disease are elaborately classified.Continued practice of Apathya Aharavihara and Manovriti, the doshas and dhatus are vitiated andcause Kitibha. In Kitibha vatakapha doshas are predominantly involved and this disease isincluded under the category of ‘Kshudra Kushtha’. Kitibha is roughly compared and acceptedwith Psoriasis of Modern Medical diagnosis. Cases characterized with well defined erythematusplaques with large adherent silvery scale with exfoliation are taken up for study.

The preliminary clinical trials with Kaisoraguggulu, Arogyavardhini and Nimbidin wereconducted earlier with different external applications groups of Samana therapy and one groups ofShodhana therapy along with rasayana treatment is taken up for clinical evaluation. This study isconducted in O.P.D and I.P.D. levels.

AYURVEDIC LITERATURE

Earlier studies in Kitibha confirmed that, this disease can be equated with Psoriasisespecially with stable plaque Proriasis. The signs and symptoms of Kitibha shown below arealmost identical with Psoriasis.

1. Ruksha - Dryness of the skin

2. Kinakharasparsa - Hard an torturous skin

3. Kandu - Itching

4. Parushya - Roughness

5. Asita - Hyperpigmentation

1 References: Charaka Samhita, Chikitsa Sthana Chapter– 7, Vidyotini Hindi Vyakhya by Vd. AmbikadattaShastry, Choukhamba Orientalia, Varanasi

916

As per Ayurvedic concept, Kitibha is classified under Kshudra Kushtha. The line oftreatment for Kitibha is based in the general treatment of kushtharoga. The main treatment issodhana followed by Samana and Rasayana therapy. Many single and compound herbal andherbomineral preparations are mentioned in Ayurvedic classics and text books. Plant origin drugslike Nimba, Bhallataka, Aragwadha, Madhusnuhi, Khadira, Majishta, Haridra, Guduchi, Bakuchi,Chakramarda, Guggulu, Karanja etc. mineral origin drugs like Rasa, Gandhaka etc and animalorigins like Gomutra, Ghee etc. are some of the drugs used alone and as ingredients in manyimportant compound preparations in various Kushtarogas.

Although there are many single and compound medicines prescribed for the treatment ofKushtharogas there is no special scientific study carried out in single or compound drugs toevaluate their therapeutic effect in a particular disease like Kitibha. So here are a few group ofdrugs are giving to evaluate their therapeutic effect in Kitibha.

MODERN CONCEPT

In Psoriasis, main abnormality is of increased epidermal proliferation due to excessivemultiplication of cells in the basal layers. The transit time of keratinosite shortened and epidermalturn over is reduced from 28 to 34 days. Even though the etiology is unknown, the factorsinvolved are genetic, biochemical, immunopathological and dermal. These factors may not be fullysufficient to develop Psoriasis, precipitating factors like trauma, infections, sunlight some drugs andemotions may cause flare up of the disease. There are different types of Psoriasis like StablePlaque Psoriasis, Guttate Psoriasis, Erythrodermic Psoriasis, Pustular Psoriasis. Of these, Stableplaque Psoriasis is dry silvery white scales. The elbow, knee, lower back are commonly involvedareas, other sites include are scalp, nails, flexures, palm and napkin area.

Guttate Psoriasis is common in children and adolescents. The rashes often appear rapidlyand lesions are small, scaly and drop-let shape. Usually the lesions plaque disappears in a fewmonths, but later it may develop into plaque pattern. Erythrodermic lesions are red and scaly.Shivering is also severe in this group due to considerable heat loss. In Pustular Psoriasis, suddenonset with myriads of small sterile pustule erupting on an erythematous base. This type isgeneralized from which is rare but serious type and it requires hospitalization. Localized form ismore common and involve mostly in palm and soles. The eruption consists of numerous smallsterile pustule lying on an erythematous base.Psoriatic arthropathy involves terminal interphalangealof toes and fingers and larger joints like sacroiliac joints and lumbarspine.Coaltar preparations,calcipotriol, retinoides, corticosteroids an ultraviolet radiation are the local measures to managePsoriasis. The systemic treatment commonly used are photo chemotherapy with PUVA, retinoides,mothotrexate and cyclosporine-A under regular specialist supervision. Systemic treatment is givenonly when the local measures fail to respond.

917

II. OBJECTIVES

To evaluate the therapeutic effect of single drugs/compound Ayurvedic formulations andShodhana therapy in the management of Kitibha (Psoriasis).

III. SAMPLE SIZE AND METHOD

The patients between the age group of 15 to 70 years in either sex presenting the clinicalsymptoms of the disease mentioned in the clinical protocol will be taken for trial. After takingdetailed clinical history careful physical examination supported with positive laboratory findings, thepatients will be put under trial either by admitting in the I.P.D. or as an outpatient. Patientssuffering from sub-acute stage of Psoriasis during that particular period with not less than 30%involvement of the body surface alone will be taken for trial. Patients having less than 10 yearsduration will be taken for the study. Patients who can report in person every week in the outpatient department will be included for clinical trial.

Number of patients in each group: 50 patients

Groups: three different groups

Type of Study: Single Blind

Level of Study: O.P.D. and I.P.D. level

Period of Study: 3 months (90 days), 15 days interval.

Follow Up: After completion of the trial, patients are advised to report in the O.P.D. of theInstitute once in every month continuously for twelve months.

DOSE SCHEDULE

Group 1:

- Arogyavardhini 500 mg along with Kaisoraguggulu 1 mg thrice daily for 3 months.

- Chakramarda Keratailam for external application

Group 2:

- Panchanimba lauha churna 2 gms, Kamadudha rasa 250 mg and haridrakhanda 3 gm(mix together in a single dose) twice daily.

Group 3:

- Snehapana for 7 days with Mahatiktaka Ghrita, Mrudu Swedana for one day.

918

- and Samsarjana

- Then after Rasayanaprayoga with Bhallataka for 3 months.

IV. INCLUSION CRITERIA

Age between 15-70 years, patients suffering from clinical syptoms like kandu, ruksha,parushya, rekhamandala, twak vigalana, nuna twak vaivarnya, ati twak vaivarnya, sub-accute stageof Psoriasis during less then ten years with not less then 30% involvement of the body surface.

V. EXCLUSION CRITERIA

Age below 15 years and above 60 years, patients suffering from any severe systemicdisease like Diabetes, Renal disease, H/O Liver disease, in the recent past VDRL positive caseswill be excluded form the trial.

Patients with other forms of Psoriasis like Guttate, Pustular, Erythrodermic, Psoriaticarthropathy and patients addicted to alcohol will not be included in the trial.

VI. CRITERIA FOR WITHDRAWL

1. Personal matters

2. Inter current illness

3. Aggravation of complaints

4. Any other

VII. CRITERIA FOR EXAMINATION AND ASSESSMENT

The diagnosis will be made on the basis of the following clinical findings.

1. Typical distribution of the Psoriatic lesions on the surface of the body such as elbow,knee, lower back, scalp, nails etc.

2. Well defined non-indurated, dry erythematous area with silvery layer scaling.

3. The candle grease sign, kobener’s phenomenon and the pin point bleeding on removalof scale.

4. Little or no itching.

5. History or previous attack or seasonal relapse.

6. Positive Histo-pathological findings.

7. Assessment of cases will be carried out weekly.

919

VIII. CRITERIA FOR ASSESSMENT OF RESULTS

Result of the treatment will be graded as follows:

1. Complete relief:

(a) 100% relief of sign and symptoms of the disease indicated under the head ofdiagnosis.

(b) Complete disappearance of the disease as evident in the colour photographicassessment.

(c) Favorable alterations in the laboratory investigations.

(d) Considerable improvement in the general well being of the patient (Both subjectivean objective).

2. Marked relief:

(a) 76% to 99% relief. Improvement of the presenting clinical symptoms of the diseaserecorded earlier.

(b) Significant change in the skin lesions observed in the photographic assessment.

(c) Satisfactory change in the laboratory investigations.

(d) Overall improvement in the well being of the patients.

3. Moderate relief:

(a) 51% to 75% relief in signs and symptoms recorded earlier.

(b) Satisfactory change in the skin lesions observed in the photographic assessments.

(c) No change in the laboratory investigations

(d) Satisfactory improvement in the general well being of the patient.

4. Mild relief:

(a) 10% to 50% improvement in the clinical symptoms of the disease.

(b) No change in laboratory findings.

(c) Mild improvement in the well being of the patient.

5. No relief:

(a) No relief or below 10% improvement

(b) No change in laboratory findings

(c) No change in photographic assessment

920

(d) No improvement in the well doing of the patient.


Data on clinical symptoms and objective tests before and after the treatment will betabulated and analyzed using appropriate statistical tools.


The progress of the trial will be monitored by CCRAS Hqrs. New Delhi. Data analysiswill be undertaken at the Monitoring Unit CCRAS Hqrs. New Delhi

XI. ETHICAL REVIEW

Each Institutional Ethical Committee (IEC) of participating centres should give clearancecertificate before the project is initiated. Patient’s information sheet and informed consent formshould be submitted alongwith project proposal for approval by IEC. Both should be maintainedin duplicate with one copy given to the patient at the time of entry to the trial.


A consolidated amount of Rs.……. /- per visit after screening and at the end ofevery further visit.





Blood: TLC, DLC, Hb%, ESR, Blood Sugar, Serum Cholesterol, VDRL

Urine: Albumin, Sugar, Bile Salt and routine investigations.

Stool: Ova, Cyst.

These investigations will be repeated every fifteen days.

921




I certify that I have disclosed all details about the study in the terms easily understood by

the patient.

Date: ___________ Signature _________________________

Name ___________________________

CONSENT BY SUBJECT



I, exercising my free power of choice, hereby give my consent to be included as asubject in the clinical trial on “Evaluation of the therapeutic effect of single drugs/compoundAyurvedic formulations and Shodhana therapy in the management of Kitibha (Psoriasis).”

Date: ________________ Name of subject__________________________

Signature or Thumb impression_______________

Date: ________________ Name of witness: _________________________



922


EVALUATION OF THE THERAPEUTIC EFFECT OF SINGLE DRUGS/COMPOUND AYURVEDIC FORMULATIONS AND SHODHANA THERAPY IN

THE MANAGEMENT OF KITIBHA (PSORIASIS)



Psoriasis is a chronic recurrent intractable disease with world wide distribution. Itconstitutes almost 10% of all skin diseases. Although Psoriasis is not a life threatening disease, itis associated with disfigurement, restrictions of activities and complications like arthritis. As far ascurative aspect of the treatment of the disease is concerned, ever after the discoveries of certainadvanced medicines, there is no effective treatment except symptomatic relief temporarily inmodern medicine.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 90 days. During treatment period,you are expected to visit the hospital in 15 days interval for clinical and physiological assessment.



At each visit, you will be supplied with sufficient quantities of drugs to last untilyour next visit. If any adverse reactions like skin allergy, nausea, vomiting andpalpitation/tremor etc., noticed during the treatment period, this should be noticed to thePrincipal Investigator.


923


EVALUATION OF SINGLE/COMPOUND/HERBOMINERAL COMPOUNDDRUGS

CASE REPORT FORM I- SCREENING

1. Name of the patient: ..............................................Age: ................ Sex: .......................

2. Address: .................................................................................................................................

3. Centre: ..................................................................


5. Patient No.

6. Group No. Group 1 Group 2


1. Age between (15 – 70 yrs)

2. Kandu

3. Ruksha

4. Parushya

5 Rekamandala

6. Twakvigalana

7. Nuna Twakvivarnya

8. Ati Twakvaivarnya


9. Acute Guttate

10. Flexular

11. Pustular

924


CLINICAL EVALUATION OF SINGLE/COMPOUND/HERBOMINERALCOMPOUND DRUGS



1. Name of the patient: .................................................... Age: ................... Sex: ..................

2. Address: .................................................................................................................................

3. Date of admission: Date of Discharge:

4. Center: .................................................................................................................................


6. Patient No:

7. Group No: 1 2 3


Illiterate 1 Read and Write 2 Primary School 3



9. Occupation:




Indicate nature of work: ...........................................................................................

Total income of the family (in Rs.): ...........................................................................


11. Income per capita per month (in Rs.):


925

Christian 4 Parsi 5

13. Marital Status: Married 1 Unmarried 2 Widow 3


14. Result: Good Response 1 Fair Response 2 Poor Response 3

No Response 4 Drop out 5 Lama 6

Death 7

CHIEF COMPLAINTS WITH DURATION

Present Absent Duration (in days)

15. Itching:

16. Dryness of the skin:

17. Roughness:

18. Circular erythemia:

19. Exfoliation:

20. Hyper Pigmentation:

21. Hypo-Pigmentation:

22. Maceration:

23. Pin point bleeding

after removal of skin

24. Papule/Pustule/Vesicle

25. Fissures:


26. Onset of disease: Acute Insidious

27. Duration of disease:

28. Treatment given so far: Ayurvedic medicine Modern Medicine

Unani Homeopathy

926

Mixed

29. Factors aggravating the disease/chief complaint:

Drug Diet Cold climate


Occupational

Positive factors may spell out: ................................................................................................

30. History of the significant past illness, Yes No

having relation with present illness.

If Yes, specify: ....................................................................................................................

FAMILY HISTORY Yes No

31. Hypertension

32. Diabetes

33. Mental disease


35. Cancer

36. Tuberculosis

37. Skin disease

38. Others, specify:.....................................................................................................................

PERSONAL HISTORY

39. Diet: Veg Non-veg Lacto ova veg

40. Sleep: Good Distributed Insomnia

41. Emotional Stress: Yes No

42. Bowel Habit: Regular Constipation

Hard Stool Loose Stool

43. Prakriti: Vata Pitta Kapha

927


44. Manasa Prakriti Satva Rajas Tamas

Satva-Rajas Satva-Tamas Sama

45. Addiction: Yes No

If yes, specify: .....................................................................................................................


46. Built: Lean Medium Heavy

47. Gait: Normal Abnormal


49. Blood Pressure (Systolic):

50. Blood Pressure (Diastolic):

51. Body Temperature:

52. Pulse:

53. Respiration:

Present Absent

54. Cyanosis:

55. Anaemia:

56. Jaundice:

57. Pigmentation:

58. Clubbing of fingers:

59. Deformation:

60. Lymphadenopathy:

928

SYSTEMATIC EXAMINATION

Normal Abnormal

61. C.V.S. with chest:

If abnormal, specify abnormalities: .....................................................................................

62. C.N.S.


63. Digestive System:

If abnormal, specify abnormalities:.....................................................................................

64. Respiratory System:


65. Uro-Genital System:


Samprapti (Pathogenesis) of the disease according to Ayurvedic Concept

Vata Pitta Kapha

66. Anubandha:

67. Anubandhya dosha:

68. Avaraka dosha:

69. Ksheena dosha:

70. Ksheena dhatu: Rasa Rakta Mamsa

Meda Asthi Majja

Shukra Oja

71. Dushya involved: Rasa Rakta Mamsa Meda

Asthi Majja Shukra


Sanchaya Prakopa Prasara

929

Sthana Sanshraya Vyakti Bheda

73. Srota Pariksha

(a). Pranavaha Srotas: Alpa-alpa Swasa (Dyspnoea)

Atisrishta Swasa (Increased respiration rate)

Abhikshna Swasa (Cheyne stroke breathing)

Kupita Swasa (Vitiated)

Sasula Swasa (Dyspnoea with pain)

(b). Udakavaha Srotas: Jihva Shosa Ostha Shosa

(Dryness tongue) (Dryness of lips)

Talu Shosa Kantha Shosa

(Dryness in Palate) (Dryness in throat)

Kloma Shosa Trishana

(Excessive thirst) (Feeling of thirst)

(c). Annavaha Srotas: Ananna Abhilasha Aruchi

(Loss of appetite) (Anorexia)

Avipaka Chardi

(Indigestion) (Vomiting)

(d). Rasavaha Srotas: Mukha Vairasya Arasadyta

(Bad taste in mouth) (Tastelessness)

Hrillas Gaurava

(Water brash) (Feeling of heaviness)

Tandra Avasada

(Drowsiness) (Depression)

Klaibya Karshya

(Loss of libido) (Emaciation)

Agnimandya

(Indigestion)

930

(e). Raktavaha Srotas: Pidaka Rakta pitta

(Boils) (Bleeding from any of theorifice)

Mukha paka Vidhradhi

(Stomatitis) (Abscess)

Charma roga Kamala

(Skin disease) (Jaundice)

(f). Mamsavaha Srotas: Arbuda Alaji

(Tumor) (Phlyctinolar conjunctivitis)

Gandamala Upjihvika

(Cervical lymphadenitis) (Epiglottis)

Adhimamsa Putimamsa

(Protuberance of flesh) (Decayed flesh/Gangrene)

(g). Medovaha Srotas: Hastapada daha Hastapada Suptada

(Burning sensation in sole (Sensory loss over theand palm) limbs)

Tandra Dehachikkanata

(Drowsiness) (Greasiness of the skin)

Alasya

(Lethargy)

(h). Asthivaha Srotas: Adhyasthi Adhidanta

(Exostosis) (Redundant teeth)

Dantashoola Asthi shoola

(Toothache) (Tenderness of the bones)

Kesha, Loma, Nakha, Samshru vikara (Any disease of hair, hair follicles, nails and moustaches)

(i). Majjavaha Srotas: Parsava shoola Bhrama

(Pain in the flanks) (Vertigo/Giddiness)

Moorchha Mithya gyana

(Syncope) (Illusion)

931

(j). Shukravaha Srotas: Klaibya Aharshana

(Infertility) (Loss of erection)

Garbhapata Santana vikriti

(Abortion) (Congenital deformity of thechildren)

(k). Artavavaha Srotas: Anartava Vandhyatva

(Amenorrhoea) (Sterility)

(l). Mutravaha Srotas Atisrashtamutram, Atibadhamutram,

Prakupita mutra Alpalpa

(Defection urination / Difficulty micturation) (Scantly urination)

Aabhikshna Bahu Mutrata

(Constant/repeated urination) (Excess urination)

Sashoola Mutrata

(Painful micturation)

(m). Pureeshvaha Srotas: Alpalpa Pureesha Sashoola Pureesha

(Scantly defecation) (Painful defecation)

Atidrava Pureesha Atigrathita Pureesha

(Watery motion) (Formation of scybala)

(n). Swedavaha Srotas: Asweda Atisweda

(Anhidrosis) (Hyper Hydrosis)

Parushya Lomaharsha

(Roughness of the skin) (Horripulation)

Anga Paridaha

(Burning sensation in the body)

72. Provisional Diagnosis

73. Final Diagnosis

74. Medical Management

75. Prinicipal drug therapy

Dose :.............................................................................................................................

932

Vehicle :.............................................................................................................................

Diet :.............................................................................................................................

Summary of findings: ..............................................................................................................

..........................................................................................................................................

..........................................................................................................................................

Date: .................................. Signature of Investigator

933



CASE REPORT FORM III – FOR PERIODICAL OBSERVATION &ASSESSMENT

(Parameters to be taken for assessment of response of therapy)

1. Centre :.............................................................................................................................

2. Code No.:.............................................................................................................................

3. Patient No.: ...........................................................................................................................

4. Group No.:.............................................................................................................................

Initially at the time

5. Clinical Parameters Symptoms

i. Itching

ii. Erythema

iii. Thickening

iv. Scaling

v. New Lesion

vi. Any other

vii. Side effects,

If any, specify: ………………………………………………………………………

6. Global Assessment

i. Objective

ii. Subjective

iii. Body Weight

iv. B.P.

After 1week

8week

7week

6week

5week

4week

3week

2week

934

v. Pulse Rate

7. Clinical Pathological

i. Urine a). Macroscopic

b). Microscopic

Date: ..................................... Signature of Investigator

935



PROFORMA PART IV – RECORD INVESTIGATION

Name of the patient: .....................................................................................................................

1. Center: ......................................................


3. Patient No:

4. Group No: 1 2 3

= = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =

Investigation At the time After 15 30 days 45 days 60 days 75 days 90 daysof admission days

1 2 3 4 5 6 7 8

Date of sample taken : .....................................................................................................................

5. Urine Sugar

6. Albumin

7. Pus Cell

8. Cast

9. R.B.C.

10. Bile Salt

11. Bile Pigment

12. Stool Ova

13. Occult Blood

14. Sterco Bilin

15. Sputum A.F.B.

936

HEAMATOLOGICAL INVESTIGATION

16. Blood

Hb%

TLC

DLC

(in thousand)

Polymorph

Lymphocyte

Basophil

Monocyte

Eosinophyl

E.S.R.

P.C.V.

Bleeding Time

Prothrombin time

BIOCHEMISTRY INVESTIGATIONS

17. Protein total

18. Albumin Globulin

Ratio

19. Blood Glucose

20. Urea

21. Uric Acid

22. Bilirubin


24. Serum AlkalinePhosphatase

937

25. Serum AcidPhosphatase

26. S. G. O. T.

27. S. G. P. T.

28. Triglycerides

29. Total lipid

30. Createnine

Positive Negative

31. Rheumatoid factor

32. V.D.R.L.

33. ASO Titre

RADIOLOGICAL INVESTIGATIONS

Normal Abnormal

34. X-ray


35. Abdomen


36. Spine (AP & Lateral view)

(Specify for region)


37. Kasa Joint (AP & Lateral view)


38. Interphalangeal Joints

(Ap & Lateral view)


938

39. Skull (AP & Lateral view)


40. I.V.P.


41. Cholecystography


42. Ba-meal follow through


43. Ba-enema

If abnormal, specify abnormalities: ...................................................................................

ELECTROGRADIUM Normal Abnormal

44. E.C.G.


45. Electro Encephalogram

If abnormal, specify abnormalities: ....................................................................................

46. CAT Scan


47. Ultra sonography of the

particular region


48. Endoscopy


49. Preliminary function test with Autospirometer

E. E.

P. E. F. R.

939

P. V. C.

Total Area Infected

940

Blank

REPRODUCTIVE AND CHILDHEALTH CARE

SEC

TIO

N - X

VII

942

BLANK

943


To evaluate the efficacy of AYUSH AG TAB in management of Anaemia, loss ofappetite, leg crams, Bodyache, Weakness during Pregnancy etc.

I. BACKGROUND:

Despite of advanced technology, a high number of women continue to die during childbirth,due to any cause, related to or aggravated by the Pregnancy or its management. Every minute,the loss of a woman, shatters a family. Woman’s health have been neglected since many decadesdue to gender inequality, poverty, illiteracy, working for the survival of mother is a human rightsimperative.

Pregnancy is a dynamic state, lot of physiological changes take place in hemodynamic andother systems of pregnant woman in order to adopt the increasing demands of the growing fetus.

Ayurvedic classics had prescribed a particular diet and drug schedule for pregnant women.These regimens support the pregnant women all through the antenatal, Intranatal and postnatalperiod. The antenatal care is mainly intended to provide optimum nourishment to mother andfetus; it prepares the reproductive system to withstand the changes during antenatal and intranatalperiods. It facilitates the metabolism of the growing fetus and prevents the obstetricalcomplications.

II AIM:

1. To care minor ailments of pregnancy like vomiting, constipation, indigestion, minoroedema etc.

2. To minimise obstetric complications such as pre-eclampsic problems, anemia, cervicaldystocia etc, to lower maternal and fetal mortality and morbidity etc.

III. Centres of the Study: 3 (three)

IV Sample size and Methods: 60

Sample size: Total case – 60, (20 each in three centres).

V. Investigational product and doses:

AYUSH –AG tablet – 500mg tab TDS from 3rd month onwards to till delivery

Vehicle – Milk or water

Follow-up: To be followed up to delivery.

944

VI. CRITERIA OF INCLUSION:

1. Pregnant women in the IIIrd month of Ist trimester with singleton pregnancy

2. Hb % between 8 and 10.5 gm/dl & Ferritin level less than 13 mg/l

3. Pregnancy not associated with any pre-existing medical illness such as TB, Epilepsy,Hypertension, Diabetes, Severe anaemia etc


5. Pregnancy not associated with any Obstetric complications such as Ante-partumhemorrhage, Multiple Gestations, Partial Hydatidiform Mole, Pre-eclamptic,Toxemia, Pregnancy Induced Hypertension, Malformations of pelvis, Rh-Incompatibility, Bad Obstetric History etc.

6. Pregnancy not associated with any Gynecological complications such as Fibroiduterus, Ovarian cyst, Cervical carcinoma, Genital prolapse etc.

VII. CRITERIA OF EXCLUSION:


2. Pregnant women in the III trimester

3. Pregnancy associated with pre-existing medical illness like TB, Epilepsy, Hypertension,Diabetes, Heart disease and severe anemia etc.

4. Grand multi-Para

5. Pregnancy associated with any Gynecological complications such as Fibroid uterus,Ovarian cyst, Cervical carcinoma, Genital prolapse etc.

6. Pregnancy associated with any Obstetric complications such as Ante-partumhemorrhage, Multiple Gestations, Partial Hydatidiform Mole, Pre-eclamptic Toxemia,Pregnancy Induced Hypertension, Malformations of pelvis, Rh-Incompatibility, BadObstetric History etc.

VIII. CRITERIA OF WITHDRAWAL:

1. 100% non-compliance

2. Irregular follow-ups

3. Pregnant woman developing severe obstetric complications

4. Non-availability of the selected cases

945

IX. ROUTINE EXAMINATION AND ASSESSMENT:

The full details of History and Physical Examination of the pregnant women will berecorded as per the Proforma (form I & IA).

First visit of the pregnant woman will be considered as the initial assessment (whether it isI or II trimester). Monthly follow up till 6th month, Fortnightly follow up –7th & 8th months,weekly follow up 9th month to till term, Oedema – weekly follow-up.

X. PERIOD OF STUDY:

7 months for each case. Total duration will be 6 months (For Ayush PG tablet) tocomplete the trial at each centre.

XI. FOLLOW-UP:

To be followed up to delivery

XIII. CRITERIA FOR ASSESSMENT OF RESULTS:

Assessment of outcome of Pregnancy:

1. To assess the outcome of delivery as abortion, live birth and still birth

2. Type of delivery as Normal vertex, Breach, Instrumental or Caesarian section

The outcome of this programme will be considered significant if;

i) The woman passes antenatal period without any major complication

ii) Delivery being normal vaginal delivery

iii) Minimal third stage bleeding with normal expulsion of placenta – uncomplicated thirdstage

iv) Giving birth to a normal, healthy, live child

XIV. STATISTICAL ANALYSIS:

Data of abortion, live birth, still birth and the type of delivery namely Normal vertex,Breach, Instrumental and Caesarian will be completed and tabulated and analyzed usingappropriate statistical methods.

XV. TRIAL MONITORING AND DATA ANALYSIS:

The progress of the trial will be monitored by field visit by monitoring unit of CCRAS.Data analysis will be undertaken at the monitoring unit of CCRAS.

XVI. ETHICAL REVIEW:

Each participating Centres Institutional Ethical Committee (IEC) or Head of the Institutionshould give clearance certificate before the trial is initiated.

946


Proforma - Antenatal Care

FORM-I: SCREENING PROFORMA

1. Code no. (of Clinical Trial)

2. Centre: __________________________________________________________________

3. Name of the subject: ________________________________________________________

4. Date of Birth: Age (in years):

5. Postal Address_____________________________________________________________

______________________________________________________________________________________

___________________________________________________________________________

Telephone number: Mobile: Landline:

CRITERIA OF INCLUSION:

6. Pregnant woman in the I and II trimesters with singleton pregnancy

7. Pregnancy not associated with any pre-existing medical illness such as Hypertension,Tuberculosis, Epilepsy, Diabetes, and severe Anemia etc.

8. Pregnant woman age between 18 to 35 years

9. Pregnancy not associated with any Obstetric complications such as Ante-partum hemorrhage,Partial Hydatidiform Mole, Pre-eclamptic Toxemia, Pregnancy Induced Hypertension,Malformations of pelvis, Rh - Incompatibility, Bad Obstetric History etc.

10. Pregnancy not associated with Gynecological complications such as Fibroid uterus, Cervicalcarcinoma, Genital prolapse, Ovarian cyst etc.



12. Pregnant woman in the III trimester

13. Pregnancy associated with any pre-existing medical illness such as Hypertension, Tuberculosis,Epilepsy, Diabetes, and severe Anemia etc.

14. Pregnancy associated with Obstetric complications such as Antepartum hemorrhage, PartialHydatidiform Mole, Pre-eclamptic Toxemia, Pregnancy Induced Hypertension, Malformations

947

of pelvis, Rh - Incompatibility, Bad Obstetric History etc.

15. Pregnancy associated with Gynecological complications such as Fibroid uterus, Cervicalcarcinoma, Genital prolapse, Ovarian cyst etc.

If ‘Yes’ to the 6-10 and ‘No’ to 11-15 above, recruit the subject for the trial, if recruited, subjectserial No._____________

Date:_____________ Signature of the Doctor / Investigator__________________

948


FORM - IA : HISTORY PROFORMA


2. Centre: __________________________________________________________________



5. Postal Address_____________________________________________________________

____________________________________________________________________________

____________________________________________________________________________


D.O. A: __________________ D.O.D:_________________


1). Education:

Husband: 1. Nil 2. Upto Primary 3. Upto middle


Wife: 1. Nil 2. Upto Primary 3.Upto middle


2). Occupation: Husband : Wife: ______________________________________________

3). Family Income per month in Rs: _____________________________________________

4). Religion: 1. Hindu 2. Muslim 3. Sikh 4. Cristian 5. Others



PRENATAL HISTORY: Gestation at first visit (in weeks):

LMP: D/M/Y Gravida: Parity:

EDD: D/M/Y

MEDICAL HISTORY:

949



FAMILY HISTORY:



2). Diseases: Chronic illness:

Hypertension: Diabetes

Genetic disorders: (specify)


Other:

3). History of Multiple births, Molar pregnancy, Large baby, Post dated labour etc.

PAST MENSTRUAL HISTORY:

Menarche:

Menstruation - Duration Flow:

- Interval:

MARITAL HISTORY:

Age of marriage: Marital life (in years):

Consanguineous: Yes/No

PERSONAL HISTORY:

Dietary Pattern - Vegetarian: Non-Vegetarian:

Likes:

Habits: Smoking/Drinking/Chewing Pan/Tobacco:

Sex Alive Stillborn Weight

HISTORY OF PREVIOUS PREGNANCY:

S.N Year Full Pre Post Abortion Type of Babyterm term term Delivery

950

1). Instrumental delivery

2). IUFD

3). Hemorrhage- Antepartum: Intrapartum:

4). Bad Obstetric History (History of 3 or > abortion or fetal deaths)

5). Neonatal death: Reason:

6). Previous Caesarian Section: Reason:

7). PET / Eclampsia:

8). Ayurveda care taken during previous pregnancies: Y/N

HISTORY OF PRESENT PREGNANCY:

1). Nausea / Vomiting 10). Vaginal bleeding: I TM - II TM - III TM-

2). Heart burn 11). Oedema

3). Indigestion 12). Hb < 8gms %

4). Constipation 13). Heart disease

5). Giddiness 14). Diabetes

6). Hypertension 15). Uterine irritation/contractions

7). Varicose veins 16). Leg cramps

8). Hemorrhoids 17). Insomnia

9). Tingling & formication

Medication:

1). Whether received TT during this pregnancy: No. of doses

2). Whether received IFA, Calcium during this pregnancy


CLINICAL EXAMINATION:

General Examination: Blood Pressure: TPR:

1. Height 2. Weight

3. Head & Neck: Eyes: Mouth:

Neck: -Lymph gland

-Thyroid gland

4. Thorax:

951

Inspection: Breast: Nipple condition - Cracks Depression

Areola condition

Auscultation: Heart: Lungs:

5. Abdomen - Obstetrical Examination:

Inspection: Incisional Scars: Yes/No Over stretching of abdomen: Yes/No

Prominent veins over the abdomen: Yes/No

Palpation: Before 28th week of pregnancy:

Fundal Height:

Head size:

After 28th week of pregnancy: -

Presentation: Position: Lie:

Auscultation: Fetal Heart Rate:



7. Pelvic Examination:

Perineum, Vulva, Vagina, Cervix, Adnexa:

Clinical pelvimetry: Adequate – Yes/No

Presentation:

8. Treatment:

Ante-natal:

1. AYUSH AG tablet – 500 mg. 1 tablet TDS, after food, from 3rd month onwards ofpregnancy up to post delivery – 3 months

Vehicle: Milk or water

Odema during pregnancy

1. AYUSH PG tablet–500mg. 1 tablet BD, after breakfast and lunch, up to 30 days


10. Remarks:

Signature of the Investigator __________________

952


RCH Proforma - Antenatal Care

FORM-II: CLINICAL ASSESSMENT

(Monthly follow up till 6th month, Fortnightly follow up –7th & 8th months,weekly follow up 9th month to till term, Oedema – weekly follow-up)

1. Code no. (of Clinical Trial):

2. Centre: ___________________________________________________________________



5. Postal Address______________________________________________________________

____________________________________________________________________________

____________________________________________________________________________

Telephone:

6. Date of assessment:

7. Month of Assessment: Initial: 1st month 2nd month

3rd month 4th month 5th month 6th month

7th month: I Fortnight: II Fortnight:


9th month to till term: I week: II week: III week:

IV week: V week: VI week:

Follow Up Record:

Visit Gestation Fundal Ht Fetal FHR B.P. T.P.R(weeks) (weeks) movements

I.

II.

III.

IV.

V.

VI.

VII.

953

VIII.

IX.

X.

XI.

XII.

XIII.

XIV.

XV.

XVI.

XVII.

XVIII.

XIX.

XX.

Associated Symptoms & Signs: (mention ‘Y’ for Yes, ‘N’ for No)

I II III IV V VI VII VIII IX X XI XII XIII XIV XV XVI XVII XVIII

Nausea

Vomiting

Heartburn

Indigestion

Constipation

Giddiness

Vaginalbleeding

Odema

Varicoseveins

Leg cramps

Tingling &formication

Insomnia

954


1.

2.

3.

4.

5.


Outcome of Pregnancy:

1. Outcome of delivery: (1. Abortion 2. Live birth 3. Stillbirth)

2. Type of delivery (1. Normal vertex 2. Breech 3. Instrumental 4. C.S)

3. Place of delivery (1. Home 2. S.C. 3. PHC/CHC 4. Nursing home 5. Hospital

4. Duration of labour (hrs):

5. Conducted by: (1. Dai 2. ANM/Nurse 3. Doctor 4. Relative 5. Other)

6. Safe Birth Kit used (1. Yes 2. No 3. Do not know)

7. Complication in the mother

(1.None 2. PPH 3. Eclampsia 4. Obstructed Labour 5. Retained Placenta)

8. Did mother require referral to higher health facility (1. Yes 2. No)

If yes, Reason————————————————————————————————

Condition of baby:

9. APGAR Scoring:

S.N Sign 0 Neonate’s 1 Neonate’s 2 Neonate’s score Score score

1. Respiratory Absent Slow, Strongeffort irregular cry

weak cry

2. Heart rate Absent Slow,<100 > 100

3. Muscle tone Limp Some Activeflexion movementof limbs

955

Severe asphyxia Score at one minute

Moderate asphyxia Score at five minutes

Mild asphyxia

No asphyxia

Stillborn/Macerated —————————————————————————

Cause —————————————————————————

10. Birth Weight (gms)

11. Sex of the baby:

12. Congenital malformation. 1. Yes 2. No


Completed:

Drop out: Reason: ____________________________

Died: Cause______________________________

Date: ______________ Signature of the Investigator___________________

4. Reflex Absent Facial Cryresponse to grimaceflicking offoot

5. Color Blue-Pale Body pink, Complete-Limbs blue ly pink

956



FORM-III: LABORATORY INVESTIGAIONS - PARAMETERS


2. Centre: ___________________________________________________________________



5. Postal Address______________________________________________________________

___________________________________________________________________________

____________________________________________________________________________

Telephone:



1). ABO & Rh: Wife - Husband:

2). VDRL _______________________

3). HIV I & II ___________________

4) HBS Ag _____________________

5. Hb gm%: ____________________

6. Urine: Routine: _________________________ Microscopic: _________________________

(Investigations 1-4 will be done initially only)

Date: __________________ Signature of Investigator ____________________

7. Hb% _____________________________

8. Clotting time _______________________

9. Bleeding time _______________________

10. Prothrombin time ____________________

11. Fibrinogen time ______________________

957

12. PCV (%) __________________________

13. Blood Sugar PP______________________

14. Blood Urea _________________________

15. Serum Creatinine _____________________

16. SGOT _____________________________

17. SGPT _____________________________

18. Serum Bilirubin ______________________

19. USG: ______________________________

20. Urine: Routine: _______________________ Microscopic: __________________________

Date:____________ Signature of the Investigator_____________________

958


To evaluate the efficacy of AYUSH PG TAB in non pathologicalmild to moderate pedal edema or generalized edema during pregnancy.

I. BACKGROUND:

Despite of advanced technology, a high number of women continue to die during childbirth,due to any cause, related to or aggravated by the Pregnancy or its management. Every minute,the loss of a woman, shatters a family. Woman’s health have been neglected since many decadesdue to gender inequality, poverty, illiteracy, working for the survival of mother is a human rightsimperative.

Pregnancy is a dynamic state, lot of physiological changes take place in hemodynamic andother systems of pregnant woman in order to adopt the increasing demands of the growing fetus.

Ayurvedic classics had prescribed a particular diet and drug schedule for pregnant women.These regimens support the pregnant women all through the antenatal, Intranatal and postnatalperiod. The antenatal care is mainly intended to provide optimum nourishment to mother andfetus; it prepares the reproductive system to withstand the changes during antenatal and intranatalperiods. It facilitates the metabolism of the growing fetus and prevents the obstetricalcomplications.

II AIM:

1. To evaluate the efficacy of AYUSH PG TAB in non pathological mild tomoderate pedal edema or generalized edema during pregnancy.

2. To minimise obstetric complications such as pre-eclampsic problems,

III. Centres of the Study: 3 (three)

IV: Sample size and Methods: 60

Sample size: Total case – 60, (20 each in three centres).

V. Investigational product and doses:

AYUSH – PG tablet – 500mg tab BD, for 30 days in cases of mild to moderate pedal edemaor generalized edema during pregnancy.

Design of study: Open trial single blind.


Follow-up: weekly.

959

VI. CRITERIA OF INCLUSION:

1. Pregnant women with non pathological mild to moderate pedal edema or generalizededema during pregnancy.

2. Pregnancy not associated with any pre-existing medical illness such as TB, Epilepsy,Hypertension, Diabetes, Severe anaemia etc


4. Pregnancy not associated with any Obstetric complications such as Ante-partumhemorrhage, Multiple Gestations, Partial Hydatidiform Mole, Pre-eclamptic Toxemia,Pregnancy Induced Hypertension, Malformations of pelvis, Rh-Incompatibility, BadObstetric History etc.

5. Pregnancy not associated with any Gynecological complications such as Fibroid uterus,ovarian cyst, cervical carcinoma, Genital prolapse etc.

VII. CRITERIA OF EXCLUSION:


2. Any other type of oedema during Pregnancy associated with pre-existing medicalillness like TB, Epilepsy, Hypertension, Diabetes, Heart disease and severe anemia etc.

3. Grand multi-Para

4. Pregnancy associated with any Gynecological complications such as Fibroid uterus,ovarian cyst, cervical carcinoma, Genital prolapse etc.

5. Pregnancy associated with any Obstetric complications such as Ante-partumhemorrhage, Multiple Gestations, Partial Hydatidiform Mole, Pre-eclamptic Toxemia,Pregnancy Induced Hypertension, Malformations of pelvis, Rh-Incompatibility, BadObstetric History etc.

VIII. CRITERIA OF WITHDRAWAL:



3. Pregnant woman developing severe obstetric complications

4. Non-availability of the selected cases


The full details of History and Physical Examination of the pregnant women will berecorded as per the Proforma (form I & IA).

960

First visit of the pregnant woman will be considered as the initial assessment (whether it isI or II trimester). Monthly follow up till 6th month, Fortnightly follow up –7th & 8th months,weekly follow up 9th month to till term, Oedema – weekly follow-up.

X. PERIOD OF STUDY:

7 months for each case. Total duration will be 6 months (For Ayush PG tablet) tocomplete the trial at each centre.

XI. FOLLOW-UP:

To be followed up to delivery

XIII. CRITERIA FOR ASSESSMENT OF RESULTS:

Assessment of outcome of Pregnancy:

1. To assess the outcome of delivery as abortion, live birth and still birth

2. Type of delivery as Normal vertex, Breach, Instrumental or Caesarian section

The outcome of this programme will be considered significant if;

i) The woman passes antenatal period without any major complication

ii) Delivery being normal vaginal delivery

iii) Minimal third stage bleeding with normal expulsion of placenta – uncomplicated third stage

iv) Giving birth to a normal, healthy, live child

XIV. STATISTICAL ANALYSIS:

Data of abortion, live birth, still birth and the type of delivery namely Normal vertex,Breach, Instrumental and Caesarian will be completed and tabulated and analyzed usingappropriate statistical methods.

XV. TRIAL MONITORING AND DATA ANALYSIS:


XVI. ETHICAL REVIEW:

Each participating Centres Institutional Ethical Committee (IEC) or Head of the Institutionshould give clearance certificate before the trial is initiated.

961


Proforma - Antenatal Care



2. Centre: ___________________________________________________________________



5. Postal Address_____________________________________________________________

___________________________________________________________________________

___________________________________________________________________________



6. Pregnant woman in the I and II trimesters with singleton pregnancy

7. Pregnancy not associated with any pre-existing medical illness such as Hypertension,Tuberculosis, Epilepsy, Diabetes, and severe Anemia etc.

8. Pregnant woman age between 18 to 35 years

9. Pregnancy not associated with any Obstetric complications such as Ante-partum hemorrhage,Partial Hydatidiform Mole, Pre-eclamptic Toxemia, Pregnancy Induced Hypertension,Malformations of pelvis, Rh - Incompatibility, Bad Obstetric History etc.

10. Pregnancy not associated with Gynecological complications such as Fibroid uterus, Cervicalcarcinoma, Genital prolapse, Ovarian cyst etc.



12. Pregnant woman in the III trimester

13. Pregnancy associated with any pre-existing medical illness such as Hypertension, Tuberculosis,Epilepsy, Diabetes, and severe Anemia etc.

14. Pregnancy associated with Obstetric complications such as Antepartum hemorrhage, PartialHydatidiform Mole, Pre-eclamptic Toxemia, Pregnancy Induced Hypertension, Malformations of

962

pelvis, Rh - Incompatibility, Bad Obstetric History etc.

15. Pregnancy associated with Gynecological complications such as Fibroid uterus, Cervicalcarcinoma, Genital prolapse, Ovarian cyst etc.


Date:______________ Signature of the Doctor / Investigator

963


FORM-I A: HISTORY PROFORMA


2. Centre: __________________________________________________________________



5. Postal Address_____________________________________________________________

____________________________________________________________________________

____________________________________________________________________________


D.O. A: D.O.D:


1). Education:

Husband: 1. Nil 2. Upto Primary 3. Upto middle


Wife: 1. Nil 2. Upto Primary 3. Upto middle


2). Occupation: Husband: ______________ Wife: ________________

3). Family Income per month in Rs: __________________________________

4). Religion:

1.Hindu 2.Muslim 3.Sikh 4.Cristian 5.Others

5). Working Status:

1. Not gainfully employed 2. Casual worker


PRENATAL HISTORY: Gestation at first visit (in weeks):


EDD: D/M/Y

964

MEDICAL HISTORY:



FAMILY HISTORY:



2). Diseases: Chronic illness: Hypertension: Diabetes



Other:

3). History of Multiple births, Molar pregnancy, Large baby, Post dated labour etc.


Menarche:


- Interval:

MARITAL HISTORY:



PERSONAL HISTORY:


Likes:





965


2). IUFD








1). Nausea / Vomiting 10). Vaginal bleeding: I TM - II TM - III TM-

2). Heart burn 11). Oedema

3). Indigestion 12). Hb < 8gms %

4). Constipation 13). Heart disease

5). Giddiness 14). Diabetes

6). Hypertension 15). Uterine irritation/contractions

7). Varicose veins 16). Leg cramps

8). Hemorrhoids 17). Insomnia

9). Tingling & formication

MEDICATION:

1). Whether received TT during this pregnancy: No. of doses

2). Whether received IFA, Calcium during this pregnancy


CLINICAL EXAMINATION:

General Examination: Blood Pressure: TPR:

1. Height 2. Weight

3. Head & Neck: Eyes: Mouth:

Neck: - Lymph gland

- Thyroid gland

4. Thorax:

966

Inspection: Breast: Nipple condition - Cracks - Depression

Areola condition

Auscultation: Heart: Lungs:

5. Abdomen - Obstetrical Examination:

Inspection: Incisional Scars: Yes/No Over stretching of abdomen: Yes/No

Prominent veins over the abdomen: Yes/No

Palpation: Before 28th week of pregnancy: -

Fundal Height:

Head size:

After 28th week of pregnancy: -

Presentation: Position: Lie:

Auscultation: Fetal Heart Rate:



7. Pelvic Examination:

Perineum, Vulva, Vagina, Cervix, Adnexa:

Clinical pelvimetry: Adequate – Yes/No

Presentation:

8. Treatment:

Ante-natal:

1. AYUSH AG tablet – 500 mg. 1 tablet TDS, after food, from 3rd month onwards ofpregnancy up to post delivery – 3 months


Odema during pregnancy

1. AYUSH PG tablet–500mg. 1 tablet BD, after breakfast and lunch, up to 30 days


10. Remarks:


967




(Monthly follow up till 6th month, Fortnightly follow up –7th & 8th months,weekly follow up 9th month to till term, Oedema – weekly follow-up)


2. Centre: ___________________________________________________________________



5. Postal Address_____________________________________________________________

___________________________________________________________________________

___________________________________________________________________________

Telephone:


7. Month of Assessment:

Initial: 1st month 2nd month 3rd month

4th month 5th month 6th month



9th month to till term: I week: II week: III week:

IV week: V week: VI week:

Follow Up Record:

Visit Gestation Fundal Ht Fetal FHR B.P. T.P.R(weeks) (weeks) movements

I.

II.

III.

IV.

V.

VI.

968

VII.

VIII.

IX.

X.

XI.

XII.

XIII.

XIV.

XV.

XVI.

XVII.

XVIII.

XIX.

XX.

Associated Symptoms & Signs: (mention ‘Y’ for Yes, ‘N’ for No)

I II III IV V VI VII VIII IX X XI XII XIII XIV XV XVI XVII XVIII

Nausea

Vomiting

Heartburn

Indigestion

Constipation

Giddiness

Vaginalbleeding

Odema

Varicoseveins

Leg cramps

Tingling &formication

Insomnia

969


1.

2.

3.

4.

5.


Outcome of Pregnancy:

1. Outcome of delivery: (1. Abortion 2. Live birth 3. Stillbirth)

2. Type of delivery (1. Normal vertex 2. Breech 3. Instrumental 4. C.S)

3. Place of delivery (1. Home 2. S.C. 3. PHC/CHC 4. Nursing home 5. Hospital

4. Duration of labour (hrs):

5. Conducted by: (1. Dai 2. ANM/Nurse 3. Doctor 4. Relative 5. Other)

6. Safe Birth Kit used (1. Yes 2. No 3. Do not know)

7. Complication in the mother

(1.None 2. PPH 3. Eclampsia 4. Obstructed Labour 5. Retained Placenta)

8. Did mother require referral to higher health facility (1. Yes 2. No)

If yes, Reason————————————————————————————————

Condition of baby:

9. APGAR Scoring:

S.N Sign 0 Neonate’s 1 Neonate’s 2 Neonate’s score Score score

1. Respiratory Absent Slow, Strongeffort irregular cry

weak cry

2. Heart rate Absent Slow,<100 > 100

3. Muscle tone Limp Some Activeflexion movementof limbs

970

4. Reflex Absent Facial Cryresponse to grimaceflicking offoot

5. Color Blue-Pale Body pink, Complete-Limbs blue ly pink

Severe asphyxia Score at one minute

Moderate asphyxia Score at five minutesMild asphyxia

No asphyxia

Stillborn/Macerated ——————————

Cause ——————————

10. Birth Weight (gms)

11. Sex of the baby:

12. Congenital malformation. 1. Yes 2. No


Completed:

Drop out: Reason: ____________________________

Died: Cause______________________________


971





2. Centre: __________________________________________________________________



5. Postal Address_____________________________________________________________

___________________________________________________________________________

___________________________________________________________________________

Telephone:




2). VDRL ____________________

3). HIV I & II ________________

4) HBS Ag ___________________

5. Hb gm%: __________________

6. Urine: Routine: ________________________ Microscopic: __________________________


Date: ________________ Signature of Investigator ____________________

7.. Hb% ___________________________

8. Clotting time ___________________

9. Bleeding time __________________

10. Prothrombin time _______________

11. Fibrinogen time ________________

972

12. PCV (%) ______________________

13. Blood Sugar PP_________________

14. Blood Urea ____________________

15. Serum Creatinine _______________

16. SGOT ________________________

17. SGPT ________________________

18. Serum Bilirubin ________________

19. USG: _________________________

20. Urine: Routine: _______________________ Microscopic: ____________________


973


“To evaluate the effect of AYUSH B.R. Leham on growth and development, immunityin infants”

I. BACKGROUND:

Approximately one million newborn deaths could be avoided every year through thepromotion of optimal newborn care practices. To be most effective, these interventions need site-specific information on existing newborn practices, barriers and facilitating factors for adoptingoptimal practices.

While India’s target under the MDG for mortality of children under age 5 is 38 per 1,000live births, the number of children who die before their fifth birthday stands at 76 at present. Infantmortality rate in India stands at 57 per 1,000 live births while neonatal mortality rate - deaths inthe first month of life - stands at 43 per 1,000 live births. According to the report, brought out bythe International Partnership for Maternal, Newborn and Child Health (MNCH), an umbrellaorganisation comprising about 240 members such as UNICEF, WHO and Save the Children,India’s average annual rate of reduction of child deaths between 1990 – 2006, has been just2.6%. If India wants to achieve the agreed targets by 2015, the required rate to reduce child andmaternal mortality will have to be 7.6% from 2007-2015.

Proper neonatal care during immediate neonatal period and infancy will bring down theInfant and neonatal mortality rate effectively, prevent ailments of childhood and ensure optimumphysical as well as mental growth of the baby. This can be done through package of the servicescomprising the nutrition, immunization and periodical health check ups. Ayurveda, the holisticsystem of medicine can render the above said package of services to the neonate in acomprehensive and integrated manner. The neonatal care described in Ayurveda is advanced andit advocates neutraceutical drugs use. Neutraceutical kinds of Rasayana drugs act as growthpromoters through their multiple actions and can prevent the ailments, which occur during theneonatal period to infantile period. The present study is under taken to promote the Neonatal andinfantile care as per Ayurveda to ensure optimum growth and development of the child.

II AIM:

1. To Ensure proper growth and development of Neonate.

2. To Enhance immunity

3. To support Physiological functions of baby like digestion, absorption and assimilation

4. To prevent frequent episodes of neonatal and childhood ailments.

III. CENTRES OF THE STUDY: 2

974

IV: SAMPLE SIZE AND METHODS:


Treatment: AYUSH– Bal Rakshak Leham – 500 mg, once in a day during first monthincrease in first month of treatment followed by increment of 500 mg every month till thecompletion of trial period

Duration of ‘Leham’ administration: Six month

Duration of study: 12 months

Design of study: Open trial single blind.

Level of Study: OPD

Follow-up: To be followed up to one year age.

V. CRITERIA OF INCLUSION:

1. Healthy, full term (AGA) baby.

2. Baby born by vaginal spontaneous delivery.

3. Baby has APGAR score in between 8 -10 at one minute.

VI. CRITERIA OF EXCLUSION:

1. Baby has APGAR score less than 8 at one minute.

2. Full Term babies with SGA and LGA.

3. Pre term and post term babies with AGA/SGA/LGA.

4. Baby born by dystocia, delayed labour.

5. Baby with congenital anomalies.

6. Baby with Rh – incompatability.

7. Baby with Pathological neonatal icterus, cyanosis, anemia and other diseases.

8. Baby with birth asphyxia

9. Baby with birth injuries like fracture, dislocation of the joint, paralysis etc.

10. Baby with HIE (Hypoxic ischemic encephalopathy).

11. Baby born to the women suffering with metabolic/hormonal disorders and TORCHinfection.

12. Baby is associated with severe septicaemia, meningitis or any other life threatening disorfer.

975

VII. CRITERIA OF WITHDRAWAL:



3. Baby developing any severe systemic diseases during the trial period.

4. Non-availability of the selected cases at due follow ups


The full details of ‘History and Physical Examination’ of the baby will be recorded as perthe Proforma (form I & IA) in hard and soft copy at first and subsequently on each visit till theage of 12 months.

First visit of the baby will be considered as the initial assessment (after the delivery).

XI. PERIOD OF STUDY: 12 months for each case. Total duration will be five years tocomplete the trial at each Centre.

X. FOLLOW-UP: To be followed up monthly till 12 months age of the baby.

XI. CRITERIA FOR THE ASSESSMENT OF RESULTS:

Assessment of outcome: Following criteria shall be adopted for the assessment-

1. The growth of children shall be assessed by means of Anthropometrical parameters notedon the growth chart.

2. Developmental assessment shall be carried out as per the Gesell’s Development Schedules

The outcome of the study will be considered significant if-

i) There is significant reduction or does not develop any severe diseases up to 12 monthsperiod.

ii) There is optimum gain in Anthropometric measurements at the given age.

iii) Reduction in or absence of seasonal disorders.

XII. STATISTICAL ANALYSIS:

Data gathered during the trial period on the preformed format including the Anthropometricmeasurements will be analyzed by using appropriate statistical methods.

XIII. TRIAL MONITORING AND DATA ANALYSIS:


976

XIX. ETHICAL REVIEW:

Each participating Centres Institutional Ethical Committee (IEC) or Head of the Institutionshould give clearance certificate before the Project as initiated. Patient’s Information Sheet andinformed consent form should be submitted along with Project proposal for approval by IEC/Headof the Institution. Both should be maintained in duplicate with one copy given to the patient at thetime of entry to

977




2. Centre: __________________________________________________________________

3. Name of the subject: _____________________Name of the mother__________________

4. Date of Birth: Age (in months):

5. Postal Address: ____________________________________________________________

___________________________________________________________________________

___________________________________________________________________________


6. Healthy, full term (AGA) baby.

7. Baby born by vaginal spontaneous delivery.

8. Baby has APGAR score in between 8 -10 at one minute.


9 Baby has APGAR score less than 8 at one minute.

10 Full Term babies with SGA and LGA.

11 Pre term and post term babies with AGA/SGA/LGA.

12 Baby born by dystocia, delayed labour.

13 Baby with congenital anomalies.

14 Baby with Rh – incompatability.

15 Baby with Pathological neonatal icterus, cyanosis, anemia and other diseases.

16 Baby with birth asphyxia

17 Baby with birth injuries like fracture, dislocation of the joint, paralysis etc.

18 Baby with HIE (Hypoxic ischemic encephalopathy).

19 Baby born to the women suffering with metabolic/hormonal disorders and TORCH infection.

20 Baby is associated with severe septicaemia, meningitis or any other life threatening disorfer.


Date: Signature of the Doctor / Investigator

978




2. Centre: __________________________________________________________________

3. Name of the Subject: ___________________Name of the Mother____________________


5. Postal Address_____________________________________________________________

___________________________________________________________________________

___________________________________________________________________________


D.O.R (Date of registration):


1). Education:

Father: 1.Nil 2.Upto Primary 3.Upto middle


Mother: 1.Nil 2.Upto Primary 3.Upto middle


2). Occupation: Father: Mother:

3). Family Income per month in Rs:

4). Religion: 1.Hindu 2.Muslim 3.Sikh

4.Christian 5.Others

5). Working Status of mother:

1. Not gainfully employed 2. Casual worker


PRENATAL HISTORY: Gestation ageat first visit (in weeks):


EDD: D/M/Y

979

MEDICAL HISTORY OF MOTHER:


Surgery: Communicable diseases:

PERSONAL HISTORY OF MOTHER:


Likes:



MOTHER’S PAST OBSTETRIC HISTORY:



2). IUFD








1. Vaginal bleeding: I TM - II TM - III TM-

2. Oedema

3. Anemia

4. Heart disease

980

5. Diabetes

6. Hypertension

HISTORY OF PRESENT LABOUR:

1. Type of labour: Normal/Abnormal (Specify)

2. Duration of labour:

3. Fetal distress: Present / Absent

4. Membranes ruptured: Spontaneously/Artificially…………….. hours before delivery

5. Character of amniotic fluid: Clear/Meconium stained/Foul smelling

Amount: Scanty/Normal/Excessive

6. Placenta and membranes: Healthy/Unhealthy Retroplacental clots Yes /No

7. Cord: Prolapsed/Around neck body

8. Drugs and treatment given ……………………..............……………………………………

BABY:

Date and time of Birth……………………Sex: Male/Female

Condition at birth: Active/Asphyxiated…………………………………….........................…

APGAR Scoring: Score at one minute Score at five minutes

Severe asphyxia

Moderate asphyxia

Mild asphyxia No asphyxia

GENERAL EXAMINATION

Moulding: Normal/Excessive/Nil

Caput: Yes/No Skin…………………………

Eyes…………........….....… Limbs………………....…….

Mouth…………………...... Genitalia………………...…..

Heart……………….....….. Lungs……………….............

Abdomen……………….... Anus………………..............

Other findings…………………………………………………....................

981

ANTHROPOMETRIC MEASUREMENTS

Weight……………

Crown Rump Length……….................. Head Circumference……..……

Mid Arm Circumference………........…. Chest Circumference………….

TREATMENT:

1.AYUSH –Bal Rakshak leham – 500mg once in a day during first month increase 500 mg everymonth up to 6 months.

REMARKS:


982



(Monthly follow up till 12th month)


2. Centre: __________________________________________________________________

3. Name of the subject: ____________________Name of the mother ___________________


5. Postal Address_____________________________________________________________

______________________________________________________________________________________________________________________________________

Telephone:


7. Month of Assessment:

Initial: 1st month 2nd month 3rd month

4th month 5th month 6th month 7th month

8th month 9th month 10th month 11th month

12th month

Temperature

Heart Rate

Respiration

Urine

Stool

Vomit

Jaundice

Weight

Parameters Initial MONTHLY ASSESSMENT

CLINICAL CHART OF BABY

I II III IV V VI VII VIII IX X XI XII

983

1. Standard 3.25 4.15 4.95 5.7 6.35 7.0 7.5 8.0 8.5 8.9 9.2 9.55 9.85(Weight in Kg)

Present weight

2. Standard(CHL in c. m.)

Present Crownto heellength

3. Standard(CRL in c. m.)

Present Crownto rump length

4. Standard(Head circumf-erence in c. m.)

Present Headcircumference

5. Standard(Chestcircumferencein c. m.)Present Chestcircumference

Standard Midarmcircumferencein c.m.

Present Midarmcircumference

Parameters Initial MONTHLY ASSESSMENT

GROWTH CHART OF BABY (ANTHROPOMETRIC ASSESSMENT)

I II III IV V VI VII VIII IX X XI XII

984




2. Centre: ___________________________________________________________________

3. Name of the subject: ____________________Name of the mother____________________


5. Postal Address______________________________________________________________

____________________________________________________________________________

Telephone:


7. Investigations:

Blood:

a) TLC, DLC, Hb%: _________________________________

b) Blood Group: ABO Rh______________________________

c) Blood Urea ______________________________________

d) Serum Creatinine __________________________________

e) SGOT __________________________________________

f) SGPT __________________________________________

g) Alkaline Phophatase _______________________________

h) Serum Bilirubin ___________________________________

Urine: Routine: ___________________________________

Microscopic: _______________________________

Any other:


985


TO EVALUATE THE EFFICACY OF AYUSH PK-AVALEHA IN PREVENTINGPOSTPARTUM COMPLICATIONS AND PUERPERIAL CARE.

INTRODUCTION:

Puerperium begins as soon as the Placenta is expelled and lasts for approximately 6weeks. During this phase woman’s body tissues, especially pelvic organs revert backapproximately to the pre pregnant state both anatomically and physiologically by the process calledinvolution. In the immediate Postpartum, apart from involution, general physiological changes suchas raise in the pulse rate, reactionary rise in temperature may be there. Bladder becomesoedematous with hyperaemic and woman becomes relatively insensitive to the raise intra vesiclepressure due to the trauma sustained to the nerve plexus during delivery, the bladder may be overdistended without any desire to pass urine. Stagnation of the urine along with a devitalized bladderwall contributes to the urinary tract infection in puerperium.

Treatment:

1. Ayush PK Avaleha: 5 gm twice daily with milk or water for 45 days after delivery.


AIMS

1. To support health status of mother during puerperium

2. To reduce perinatal mortality and morbidity

3. To prevent complications of Postpartum

4. To ensure early sub involutions of uterus.

V. CRITERIA OF INCLUSION:

1. Age between 20 – 35 years

2. Puerperium without any severe complications like Post partum haemorrhage,

Sub involution of uterus etc.

3. Normally delivered /Caesarian delivery

4. Not associated with postnatal eclampsia, Puerperal psychosis, Post-gestational diabetes etc.

986


1. Puerperium associated with severe Postpartum haemorrhage

2. Cases with acute puerperal inversion of Uterus

3. Cases associated with Postnatal eclampsia, Puerperal psychosis, Post gestational diabetes etc.

4. Puerperal woman aged below 15 and above 35 years of age.

VII. CRITERIA OF WITHDRAWAL:

1. Patients not complying with treatment

2. Development of complications like haemorrhage, convulsion etc.

3. Patients left the study in between


The full details of history and physical examinations of the patients will be recorded as perthe Proforma (Forms 1& 1A) Clinical assessment will be done before drug administration on1st , 2nd , 3rd , 4th ,5th ,6th ,7th , 15th ,30th 45th day during drug treatment period ,30th ,60th

,90th day during follow-up (Form-II). Laboratory investigations carried out according to Form-III.

IX. PERIOD OF STUDY:

3 months for each case. Total duration will be 1 year to complete the trial at each centre.

X. FOLLOW –UP: The follow-ups will be carried out after 30th, 60th, and 90th day.

XI. CRITERIA FOR ASSESSMENT OF RESUTS:

Completion of puerperium without any complications, early involution of Uterus, properonset and maintenance of lactation, improvement in general health status of mother will beconsidered as significant improvement.

XII. STATISTICAL ANALYSIS:

Data on involution of Uterus, prevention of the complications of puerperium, lactationmaintenance will be tabulated and analysed using appropriate statistical methods.

XIII. TRAIL MONITORING AND DATA ANALYSIS:

The progress of the trial will be monitored by field visits by monitoring unit of CCRAS.Data analysis will be undertaken at monitoring unit of CCRAS.


Each participating Centres Institutional Ethical Committee (IEC) or Head of Institutionshould give clearance certificate before the Project is initiated. Patients information sheet andinformed consent form should be submitted in duplicate with one copy given to the patient at thetime of entry to the trial.

987




2. Centre: ___________________________________________________________________



5. Postal Address_____________________________________________________________

___________________________________________________________________________

____________________________________________________________________________




2. Puerperium without any severe complications like Post partum haemorrhage, Subinvolution ofuterus etc.

3. Normally delivered

4. Not associated with postnatal eclampsia, Puerperal psychosis, Post-gestational diabetes etc.




3. Cases associated with postnatal eclampsia, Puerperal psychosis, Post gestational diabetes etc.


5. If ‘Yes’ to the 6-9 and ‘No’ to 10-13 above, recruit the subject for the trial, if recruited,

subject serial No._____________


988




2. Centre: __________________________________________________________________



5. Postal Address______________________________________________________________

___________________________________________________________________________

___________________________________________________________________________


D.O. A: D.O.D:


1). Education:

Husband:

1. Nil 2. Upto Primary 3.Upto middle


Wife:

1.Nil 2.Upto Primary 3.Upto middle


2). Occupation: Husband: Wife:


4). Religion: 1.Hindu 2.Muslim 3.Sikh 4.Cristian 5.Others



PRENATAL HISTORY: Gravida: Parity:

LMP: D/M/Y

EDD: D/M/Y

989

MEDICAL HISTORY:



FAMILY HISTORY:






Other:

3). History of Multiple births:


Menarche:


- Interval:

MARITAL HISTORY:



PERSONAL HISTORY:


Likes:





990


2). IUFD



5). Neonatal death – Reason:

6). Previous Caesarian Section - Reason:

7). PET Eclampsia:

LABOUR HISTORY: Date Time:

Type of Delivery:

Duration of Labour: First stage: Hrs. mnts

Second stage: Hrs mnts

Third stage: Hrs mnts

Condition of Baby: Active / Asphyxiated / still birth / macerated

APGAR Score: __________________

Treatment at Birth: ________________

Delivery of placenta & membranes:

Delivered Time:___________________

Spontaneous / Helped out / Manually Removed:

Type of Placenta:

Placenta & Membranes: Complete / Incomplete:

Weight: __________ Cord length: ___________ Cord insertion: ______________

Any abnormality:

Total blood loss: ml

Perineum: Intact / Episiotomy:

Laceration

Medicines given:

Condition of mother following delivery:

991

Pulse: B.P Temp.

Uterus: Hard / Soft

Vaginal bleeding:

POSTNATAL HISTORY:

Fever: Condition of Breast:

Excessive vaginal bleeding: Onset of Milk

Breast fullness with fever: Mental condition:

Burning on passing urine: Foul smelling vaginal discharge:

Puerperal Psychosis:

TREATMENT:

Mother:

1. Ayush - PK Avaleha : 5 gm twice daily with milk or water for 45 days after delivery

- Vehicle: Milk or water


992


FORM-II: CLINICAL ASSESMENT


2. Centre: ____________________________________________________________________



5. Postal Address_____________________________________________________________

___________________________________________________________________________

___________________________________________________________________________

Follow-up chart of puerperium:

CLINICAL CHART OF PUERPERIUM

I day II day III day IV day V day VI day VII day

Date:

Temperature Fundal (in cm)height above

Pubic symphysis

M E M E M E M E M E M E M E

F

104.9

104.0

103.1

102.2

101.3

100.4

99.5

98.6

97.7

96.8

95.9

C

40.5

40

39.5

39

38.5

38

37.5

37

36.5

36

35.5

20

17.5

15

12.5

10

7.5

5

2.5

993

Pulse M

E

Respir M

ation E

B.P M

E

Lochia

Urine

Motion

Weight

Episiotomy wound

a). Discharges-

Yes/No

(Blood/Pus/Serous)

b).Colour of the

wound –

Pinkish/other

c). granulation

formed /not

d). condition of

the wound –

healthy/not healthy

Lactation


994


FORM-III: LABORATORY INVESTIGATIONS - PARAMETERS


2. Centre: __________________________________________________________________

Name of the subject: __________________________________________________________


5. Postal Address_____________________________________________________________

___________________________________________________________________________

___________________________________________________________________________

Telephone:




2). VDRL ________________

3). HIV I & II _____________

4) HBS Ag --------------------________________

5. Hb gm%: ___________________

6. Urine: Routine: _______________________ Microscopic: __________________________


Date: _____________ Signature of Investigator ____________________

7. Hb% ___________________________

8. Clotting time ___________________

9. Bleeding time __________________


11. Fibrinogen time ________________

12. PCV (%) ______________________

995

13. Blood Sugar PP_________________

14. Blood Urea ____________________


16. SGOT ________________________

17. SGPT ________________________

18. Serum Bilirubin ________________

19. USG: _________________________



996


TO EVALUATE THE EFFICACY OF AYUSH SS-GRANULES TO ENSUREQUALITY & QUANTITY OF BREAST MILK

I INTRODUCTION

There will be increased thirst in early puerperium is due to loss of fluid during labour in thelochia, diuresis and perspiration. Slight intestinal paresis leads to constipation. Colostrum secretionfrom breasts becomes more abundant.

Post-natal care mainly aims at management of postnatal ailments and supporting involutionof genital organs, onset and maintenance of lactation, betterment of general health status of mother.

II. AIMS:

1. To ensure proper lactation and quality, quantity of breast milk

III. Centres of the Study: 03 (Three)

IV. Sample size and Methods:


Ayush SS granules: 10gm. BD, after breakfast and at bedtime through out lactation period.


Duration: 3 months

Design of the Study: Open trial

The progress of the trial will be monitored by field visits by monitoring unit of CCRAS. Dataanalysis will be undertaken at monitoring unit of CCRAS.


Each participating Centres Institutional Ethical Committee (IEC) or Head of Institutionshould give clearance certificate before the Project is initiated. Patients information sheet andinformed consent form should be submitted in duplicate with one copy given to the patient at thetime of entry to the trial.

Efficacy parameters: Test for quality & quantity of milk-

Parameters of Assessment:

997

1. Improvement in Quantity of milk

2. Assessment of pre and post treatment serum prolactin levels

3. Assessment of weight gain by child

4. Analysis of breast-milk samples [Proteins, Lactose (Carbohydrate), Fat, Minerals(Calcium, Phosphorous)]

5. Global Investigator’s assessment

6. Global Subject’s assessment

7. Safety Evaluation

998




2. Centre: ___________________________________________________________________



5. Postal Address_____________________________________________________________

____________________________________________________________________________

___________________________________________________________________________




7. Insufficient lactation (Indicators of insufficient lactation: 1.lactating mother feels that secretion isnot sufficient,2. Baby cries a lot,3. Inadequate weight gain,4.Development of mal-nutrition)

8. Puerperium without any severe complications like Post partum haemorrhage, Subinvolution ofuterus etc.

9. Normally delivered

10. Not associated with Postnatal eclampsia, Puerperal psychosis, Post-gestational diabetes etc.




13. Cases associated with Postnatal eclampsia, Puerperal psychosis, Post gestational diabetes etc.


15. Mastitis and breast abscess



999




2. Centre: ___________________________________________________________________



5. Postal Address_____________________________________________________________

___________________________________________________________________________

___________________________________________________________________________


D.O. A: D.O.D:


1). Education:

Husband:



Wife:



2). Occupation: Husband: Wife:


4). Religion: 1.Hindu 2.Muslim 3.Sikh 4.Cristian 5.Others



PRENATAL HISTORY: Gravida: Parity:

LMP: D/M/Y

EDD: D/M/Y

1000

MEDICAL HISTORY:



FAMILY HISTORY:






Other:

3). History of Multiple births:


Menarche:


- Interval:

MARITAL HISTORY:



PERSONAL HISTORY:


Likes:





1001


2). IUFD



5). Neonatal death – Reason:

6). Previous Caesarian Section - Reason:

7). PET Eclampsia:

LABOUR HISTORY: Date Time:

Type of Delivery:

Duration of Labour: First stage: Hrs. mnts

Second stage Hrs mnts

Third stage Hrs mnts

Condition of Baby: Active / Asphyxiated / still birth / macerated

APGAR Score:

Treatment at Birth:

Delivery of placenta & membranes:

Delivered Time:

Spontaneous / Helped out / Manually Removed:

Type of Placenta:

Placenta & Membranes: Complete / Incomplete:

Weight: Cord length: Cord insertion:

Any abnormality:

Total blood loss: ml

Perineum: Intact / Episiotomy:

Laceration

Medicines given:

1002

Condition of mother following delivery:

Pulse: B.P Temp.

Uterus: Hard / Soft

Vaginal bleeding:

POSTNATAL HISTORY:

Fever: Condition of Breast:

Excessive vaginal bleeding: Onset of Milk

Breast fullness with fever: Mental condition:

Burning on passing urine: Foul smelling vaginal discharge:

Puerperal Psychosis:

TREATMENT:

AYUSH SS granules: 10gm. BD, after breakfast and at bedtime through out lactation period.



1003


FORM-II: CLINICAL ASSESMENT


2. Centre: ____________________________________________________________________

3. Name of the subject: _________________________________________________________


5. Postal Address______________________________________________________________

____________________________________________________________________________

____________________________________________________________________________

Efficacy parameters: Test for quality & quantity of milk

Parameters of Assessment:

1. Improvement in Quantity of milk


3. Assessment of weight gain by child

4. Analysis of breast-milk samples [Proteins, Lactose (Carbohydrate), Fat, Minerals (Calcium,Phosphorous)]

5. Global Investigator’s assessment

6. Global Subject’s assessment

7. Safety Evaluation

1004


FORM-III: LABORATORY INVESTIGATIONS - PARAMETERS


2. Centre: ___________________________________________________________________



5. Postal Address_____________________________________________________________

___________________________________________________________________________

____________________________________________________________________________

Telephone:


7. Investigations: Blood(Routine)


2). VDRL ________________

3). HIV I & II _____________

4) HBS Ag ______________________________

5. Hb gm%: ___________________





Date: _____________ Signature of Investigator ____________________

7. Hb% ___________________________

8. Clotting time ___________________

9. Bleeding time __________________


1005

11. Fibrinogen time ________________

12. PCV (%) ______________________

13. Blood Sugar PP_________________

14. Blood Urea ____________________


16. SGOT ________________________

17. SGPT ________________________

18. Serum Bilirubin ________________




1006

BLANK

1007

CLINICAL SAFETY OF SOME

AYURVEDIC AND SIDDHA DRUGS

SEC

TIO

N - X

VIII

1008

Blank

1009

Drug: Study Code:


OPEN OBSERVATIONAL STUDY ON CLINICALSAFETY OF SELECTED AYURVEDIC AND SIDDHA

HERBOMINERAL AND METALLIC PREPARATIONS


1010

Blank

1011

I. BACKGROUND

The use of metals in therapeutic drugs has become increasingly important over the lastcouple of decades; Ayurveda recognizes their use long before that. Rasashastra, one among thesubspecialties of Ayurvedic Pharmaceuticals and Siddha classics have specified therapeutic use ofmetals and minerals in the form of Bhasmas and Rasakalpas. As these drugs required in lesserdoses, causes no distaste unlike herbal drugs and faster in action, these practices became popularand widely accepted and safely used since long.1

Heavy metals are chemical elements with a specific gravity that is at least 5 times thespecific gravity of water. There are 35 metals that concern us because of occupational orresidential exposure; 23 of these are the heavy elements or “heavy metals”: antimony, arsenic,bismuth, cadmium, cerium, chromium, cobalt, copper, gallium, gold, iron, lead, manganese, mercury,nickel, platinum, silver, tellurium, thallium, tin, uranium, vanadium, and zinc (Glanze 1996).Interestingly, small amounts of these elements are common in our environment and diet and areactually necessary for good health, but inappropriate dosage forms of any of them may causeacute or chronic toxicity (poisoning).

Some well-known toxic metallic elements with a specific gravity that is 5 or more timesthat of water are Arsenic, 5.7; Cadmium, 8.65;Iron, 7.9;Lead, 11.34; and Mercury, 13.546 (Lide1992).2

Articles ( JAMA, Dec.15, 2004, Vol.292, No.23) published in some journals havementioned about the toxicity, presence of heavy metal contents of certain Ayurvedic Classical/Proprietary preparations which is creating misconceptions among scientific communities and generalpublic regarding the safety of Ayurvedic/Siddha Rasa Kalpas and Bhasmas.


OPEN OBSERVATIONAL STUDY ON CLINICAL SAFETY OF SELECTED(RASA MANIKYA RASA) AYURVEDIC AND SIDDHA HERBOMINERAL AND

METALLIC PREPARATIONS.

References

1. RasaRatna Samuchchaya,chapter 28/1.

2. http://www.lef.org/protocols/: Heavy Metal Toxicity

3. Rasa Ratna Samuchchaya,chapter 5/11,20,30,147.

1012

The classics of Ayurvedic Rasashastra and siddha system have specified different methodsof preparation and operational procedures since from the collection of raw drugs their purification,processing, method of use, dosage forms etc. The raw drugs and finished products, if notprocessed and preserved as per the classical literature specified, they may lead to improperfinished product with contaminants and may lead to toxic symptoms3. Thus this project isundertaken to assess the heavy metal toxicity in patients receiving Ayurvedic /siddha preparations.

II. OBJECTIVE:

Observe the clinical/biochemical changes in subjects receiving Rasa Manikya Rasa, anAyurvedic Herbomineral / Metallic preparations for ensuring Clinical safety.

III. CENTRE:




Type of Study : Open

Level of Study : OPD

Period of Treatment : 15 days

Period of Study : 6 months

Details of treatment schedule

a) Drug: Rasa Manikya Rasa

b) Indicated conditions: Skin disorders, Dermatitis, Eczema etc.

c) Dosage schedule and duration: 60 mg BD for 15 days

d) Combinations with the main drug if any: Rasa Manikya Rasa 60 mg. in 2 gms. ofChopachini Churna.

e) Anupana [Vehicle]: Lukewarm water

V. CRITERIA FOR INCLUSION:

1. Patients above 20 years and below 60 years of age.

2. Biochemical investigations for heavy metals at 0 day of assessment within the range.

3. Clinically diagnosed cases of Skin disorders, Dermatitis, Eczema etc.

1013

VI. CRITERIA FOR EXCLUSION:

1. Serum metallic levels of any of the metals exceeding permissible range at day 0 ofassessment

2. Age below 20 years & above 60 years

3. Known renal or Hepatic Pathology (Confirm by Clinical/Biochemical parameters)

4. Chronic Industrial Exposure

5. Patient receiving any other mineral preparation other than trial drug.

6. Major neuro-Psychiatric abnormalities

7. Chronic Smokers/Tobacco consumers




Screening of the patient as per case record form - I. The full details of history andphysical examination of the subjects will be recorded as per case report forms (Case report formII). Clinical and physiological assessment (Case report form -III) and laboratory investigations(Case report form -IV) will be done before treatment, at 0 day, 7th & 15thdays.


Data on clinical symptoms and objective tests before and after the treatment will betabulated and analyzed using appropriate statistical tools. The data generated at the Institute on thetrial drug will have to be communicated to the Statistical Officer of CCRAS from time to timethrough e-mail.

X. CRITERIA FOR ASSESSMENT OF OUTCOME OF STUDY

The assessment of progress & outcome of the study are assessed on the basis of clinicaland biochemical investigations.


The Statistical Section, CCRAS, Hqrs, New Delhi will undertake the monitoring ofprogress of the trial and data analysis.

1014

XII. ETHICAL REVIEW


B. Data and safety monitoring board: A Data and safety monitoring board (DSMB) atHqrs. will carefully monitor the data and side effects during the period of study and put ina place where by prompt reporting of adverse events occur. The data will be reviewed asevery 20 participants entered the study and administered the trial drugs. The research teamwill report immediately to the PI and Data Monitoring Board if, any life threateningconditions whether they are perceived to be study related or not. The Board decideswhether the adverse effects warrant discontinuation of the study protocol. Protocols will bewritten and approved for the treatment of study related adverse events.

XIII. TRAVELLING EXPENSES

A consolidated amount of Rs.100/- per visit 0 day, 7th & 15thdays (Total Rs.300/-) willbe paid to the patient at the end of the study.





1015





Date: _______________ Signature of the Investigator: ___________

Name: ____________________________

CONSENT BY SUBJECT

I have been informed to my satisfaction, by the attending physician, the purpose of the trialand the nature of drug treatment and follow-up, including the laboratory investigations to beperformed to monitor and safeguard my body functions.


I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “Open Observational Study on Clinical Safety of Selected (RasaManikya Rasa) Ayurvedic and Siddha Herbomineral and Metallic Preparations.”





Relationship ___________________________________


1016






The use of metals in therapeutic drugs has become increasingly important over the lastcouple of decades; Ayurveda & Siddha recognizes their use long before that. The AyurvedicRasashastra, one among the subspecialties of Ayurvedic & Siddha Pharmaceuticals has specifiedtherapeutic use of metals and minerals in the form of Bhasmas and Rasakalpas. As these drugsrequired in lesser doses, causes no distaste unlike herbal drugs and faster in action, these practicesbecame popular and widely accepted and safely used since long.

The Ayurvedic preparation identified for the study, Rasa Manikya Rasa is being frequentlyprescribed by the practitioners since time immemorial for various common ailments encountered inthe general practice and found safe and effective.

However, considering the eco-climatic changes traces of certain unwanted substances maylead to untoward effects. Thus this project is undertaken to assess the clinical safety in subjectsreceiving Ayurvedic preparations.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 15 days to complete. During thisperiod, you are expected to visit the hospital 3 times (0, 7th & 15th days) for clinical, bio-chemicaland physiological assessment.





1017





BEFORE TREATMENT

(Enter a (�) in the appropriate box)

1. Centre: ………………..……….





6. Address Permanent postal address with phone number & email if any.

..............................................................................................................................

..............................................................................................................................


1. Age above 20 & below 60 years

2. Biochemical investigations for heavy metals at0 day of assessment within the range.

3. Clinically diagnosed cases of Skin disorders, Dermatitis, Eczema etc.

EXCLUSION CRITERIA Yes (1) No (0)

4. Serum metallic levels of any of the metals exceeding permissible range at day 0 of assessment

5. Age below 20 & Above 60 years

6. Known Renal or Hepatic Pathology

1018



9. Major Neuro- Psychiatric abnormalities

10. Chronic Smokers / Tobacco Consumers.

A patient is eligible for admission to the trial,only if sl. No.1 - 3 are “yes” & if the sl.No. 4-10 are “no”.

Date:___________________ Signature of Investigator:__________________

1019





1. Centre: ………………..……….






7. Address Permanent postal address with phone nu,ber & email if any.

8. Educational status: Illiterate 1 Literate 2 Matriculation 3

Graduate 4 PG 5

9. Annual Income Rs.

Less than Rs. 60,000/- (1) More than Rs. 60,000/- (2)

10. Occupation:

A. Current occupation related to significant exposure of dust, chemical, smoke orheavy metal.

Yes If yes, details

No __________

B. Previous Occupation: [in last 3 years]

Was there any significant exposure to dust, chemicals smoke or heavy metal

Yes If yes, details

1020

No __________


a. H/o of intake of any Ayurvedic medicine yes-1 No-2for the past 3 months

b. Disease/Cause for which therapy was taken —————————————————

c. Name of the Drug 1. —————————————————————

(Including brand name, 2. —————————————————————

Pharmacy, Batch no. & 3. —————————————————————

Dosage) 4. —————————————————————

5. —————————————————————

d. Date of starting the treatment: ——————————————————————

e. Duration of treatment ——————————————————————

f. Date of termination of therapy: ——————————————————————

g. Reason for termination of Therapy: ————————————————————

h. Cured / Dropped Out etc. ———————————————————————

12. History of Past illness:

Yes-1 No-2

If yes, details…………………………………………….....................................................


2. Previous episode


4. Treatment given so far

1021

13. Personal History:

Diet Veg (1) Non-veg. (2)

Sleep Satisfactory: (1) Unsatisfactory (2)

Constipation Yes (1) No (2)

History of Environmental tobacco

Smoking exposure Yes No Duration

Tobacco chewing

Betel chewing

Prakriti


Vata-kaphaj 4 Vata-pittaj 5 Pitta-kaphaj 6

Sama 7

14. HISTORY OF PRESENT ILLNESS:

Chief complaints & Duration

15. DIAGNOSIS:

OTHER SPECIFIC SYMPTOMS IF ANY WITH DURATION (0, 7th & 15thday)

Present-1 Absent-2 If present thenduration in months

1. Burning in throat (As,Hg)

2. Cough (Hg)

3. Difficulty in Swallowing (As)

4. Nausea (As, Cd, Hg, Pb)

5. Vomitting (As, Cd, Hg, Pb)

6. Excessive Salivation (Cd)

1022

7. Thirst (Pb)

8. Yellowing of teeth (Cd)

9. Diarrhea (As,Cd, Hg, Pb)

10. Abdominal Pain(As,Cd,Hg, Pb)

11. Garlic odor in the breath (As)

12. Metallic taste in mouth (Hg, Pb)

13. Difficulty in breathing (As, Cd, Hg)

14. Chest Pain (Cd)

15. Tightness/Burning in Chest(Hg)

16. Oliguria/Anuria (As,Pb)

17. Headache (As,Hg)

18. Irritability (As)

19. Muscular Weakness (As,Hg,Pb)

20. Convulsions (As)

21. Loss of Appetite-Anorexia (Pb, As, Hg)

22. Fever (As,Cd)

23. Loss of Taste (Cd)

24. Loss of Smell (Cd)

25. Pain in joints (Cd, Pb)

26. Visual Disturbances (Hg)

27. Forgetfulness (Hg)

28. Lack of Concentration (Pb)

29. Anxiety (Hg)

1023

30. Emotional instability/Mood swings (Hg, Pb)

31. Insomnia (Hg)

32. Weight Loss (Pb)

33. Shaky hands (Pb)

34. Numbness (Pb)

35. Vertigo (Pb)

36. Hallucinations (Pb)

37. Loss of consciousness

Note. Similar Signs/symptoms appearing as result of disease process /previous treatmentshould be noted separately to avoid misinterpretation.

16. PHYSICAL EXAMINATION

Height (cm) ________________

Weight (kg) ________________

________________

Pulse rate (per min) ________________

Respiration rate (per min) ________________

Blood Pressure (mm Hg) ________________

Systolic ________________

Diastolic ________________

Body temperature ( o F) ________________

Weight (kg.)B.M.I. ———————

Height (meters)2{ }

1024

Absent(0) Present (1)

Pallor

Lymphadenopathy

Cyanosis (As)

Clubbing nails

Edema

If present, specify

Bluish line on Gingiva (lead line)

Skin & nails

Erythroderma (As)

Hyperkeratosis (As)

Hyperpigmentation (As)

Exfoliative Dermatitis (As)

Aldrich Mees Lines (As) (Transverse white striae on fingernails)

17. SYSTEMIC EXAMINATION Normal (0) Abnormal (1)

CVS


CNS


Respiratory system


1025

Digestive system


Urogenital system


Date:_______________ Signature of investigator:_________________

1026



CASE REPORT FORM III – CLINICAL AND PHYSIOLOGICAL ASSESSMENT(0, 7th & 15th day)

1. Centre: ………………..……….






7. Contact no. (Permanent postal address and phone number)

..............................................................................................................................Email ID ..............................................................................................................


9. Name of Formulation ...........................................................................................................

I. ASSESSMENT OF THE TREATING CONDITION (The investigator should record theprogress of the treating condition viz. Improvement, adverse effects etc.)

II. OTHER SPECIFIC SYMPTOMS WITH DURATION (IF ANY)

Present-1 Absent-2 Duration


2. Cough (Hg)




1027


7. Thirst (Pb)



10. Abdominal Pain(As,Cd,Hg, Pb)


12. Metallic taste in mouth (Hg,Pb)

13. Difficulty in breathing (As,Cd,Hg )

14. Chest Pain (Cd)

15. Tightness/Burning in Chest (Hg)






21. Loss of Appetite-Anorexia (Pb,As,Hg)

22. Fever (As,Cd)







1028

29. Anxiety (Hg)


31. Insomnia (Hg)



34. Numbness (Pb)

35. Vertigo (Pb)



III. PHYSICAL EXAMINATION

1. Height (cm) ________________

2. Weight (kg) ________________

3. ________________

4. Pulse (per min) ________________

5. Respiration rate (per min) ________________

6. Blood Pressure (mm Hg) ________________

7. Systolic ________________

8. Diastolic ________________

9. Body temperature ( o F) ________________


10. Pallor

11. Lymphadenopathy

12. Cyanosis (As)


Height (meters)2{ }

1029

13. Clubbing nails

14. Edema

If present, specify General Local (Area) _________________

15. Bluish line on Gingiva (lead line)

Skin & nails

16. Erythroderma (As)

17. Hyperkeratosis (As)

18. Hyperpigmentation (As)

19. Exfoliative Dermatitis (As)

20. Aldrich Mees Lines (As) (Transverse white striae on fingernails)

IV. SYSTEMIC EXAMINATION Normal (0) Abnormal (1)

CVS


CNS


Respiratory system


Digestive system


Urogenital system



*Note: Separate sheet of this form should be used for separate visits i.e 3 sheets for3 visits.

1030




CASE REPORT FORM IV – LABORATORY INVESTIGATIONS(0, 7th & 15thday)

1. Centre: ………………..……….







Urine Examination

8. Routine____________ Microscopic___________

9. Urinary levels of heavy Metals As ___________

Pb___________

Cd___________

Hg___________

Haematological Investigations

10. Serum Analysis for heavy Metals: As ___________

Pb ___________

Cd ___________

Hg ___________

1031

11. Hb (g/dl) _______________________________

12. TLC (Cells/Cu.mm.) ______________________

DLC

13. P (%) __________________

14. L(%) __________________

15. M (%) __________________

16. E(%) __________________

17. B (%) __________________

18. ESR (1st hour.) (mm) __________________

Blood Sugar

19. Fasting (mg./dl) __________________

20. Uric acid (mg./dl) __________________

Kidney function tests (Sl.No.)

21. B.Urea (mg./dl) __________________

22. S.Creatinine (mg./dl) __________________

Liver function tests (Sl.No.)

23. Total proteins (g./dl) __________________

24. Albumin (g. /dl) __________________

25. Globulin (g. /dl) __________________

26. A/G Ratio __________________

27. S.Bilirubin(mg./dL)

a. Total __________________

b. Direct __________________

1032

c. Indirect __________________

d. SGPT. (IU/L) __________________

e. SGOT (IU/L) __________________

28. Alk. Phosphates (KA units) __________________

29. X-ray chest (PA View) _____________________________________________

30. USG Whole Abdomen _____________________________________________

_____________________________________________

31. ECG (0,12 WEEK& if symptoms suggest sos) _________________________________


Date:______________ Signature of the Research Fellow/Investigator _______________

Place:_____________

Note:

• Investigations from Sl. No. 26-28 are to be done at 0 & 15thday.

*Note: Separate sheet of this form should be used for separate visits i.e. 3sheets for 3visits.

1033

ANNEXURE-I

HEAVY METAL TOXICITY-GENERAL CONSIDERATIONS

Heavy metals become toxic when they are not metabolized by the body and accumulatein the soft tissues. Exposure to toxic heavy metals is generally classified as acute, 14 days or less;intermediate, 15-354 days; and chronic, more than 365 days (The Agency for Toxic Substancesand Disease Registry –ATSDR). Additionally, acute toxicity is usually from a sudden orunexpected exposure to a high level of the heavy metal (e.g., from careless handling, inadequatesafety precautions, or an accidental spill or release of toxic material often in a laboratory,industrial, or transportation setting). Chronic toxicity results from repeated or continuous exposure,leading to an accumulation of the toxic substance in the body. Chronic exposure may result fromcontaminated food, air, water, or dust; living near a hazardous waste site; spending time in areaswith deteriorating lead paint; maternal transfer in the womb; or from participating in hobbies thatuse lead paint or solder. Chronic exposure may occur in either the home or workplace. Symptomsof chronic toxicity are often similar to many common conditions and may not be readilyrecognized. Routes of exposure include inhalation, skin or eye contact, and ingestion (ATSDRMMGs and ToxFAQs; Anon. 1993; WHO 1998; International Occupational Safety andHealth Information Centre 1999; Roberts 1999; Dupler 2001; Ferner 2001).

Reference Range of some Toxic heavy Metals*

Medical testfor Screening

Urine (best),hair, Fingernails

Blood, UrineHair

S.No.

1.

2.

Name ofthe mental

Arsenic(As)

Lead

Ref. Range in blood(whole Blood)

Arsenic (blood): ReportingLimit: 10ng/mlReference Range: Up to 10 ng/mlPhysiologic arsenic concentrationsin unexposed individuals areusually less than 10 ng/ml;however, the total arsenicconcentration may be markedlyincreased after dietaryconsumption of seafood.

Lead (blood): Reporting Limit:1.0 ug/dlNormal (unexposed population):

Ref. Range inurine

Arsenic, Urine:0.0-52.7 ug/lArsenic, Urine (24hour) 0.0-63.9 ug/dArsenic per gramcreatinine < 35 ug/g CRT

Lead, Urine 0-23ug/LLead, Urine (24-

1034

3.

4.

Cadmium

Mercury

Children and adults < 10 ug/dlExposed: Children (0-6 years)> 10 ug/dlAdults (occupational exposure)OSHA action level 40ug/dlBEI (Biological Exposure 30ug/dlIndex) (sampling time notcritical)BAT (Biological Tolerance 70ug/dlValue) (sampling time notcritical)Toxic: Children (0-6 years) >70 ug/dlAdults > 80 ug/dl

0.0 - 5.0 mcg/L

Mercury (blood): (Mercurymeasured as total mercury(inorganic, organic, and metallic).Reporting Limit: 5 ng/mlReference Range: Up to 15 ng/mlNormal (unexposed population):less than 8 ng/mlExposed:BEI (Biological ExposureIndex): 15 ng/ml (totalinorganic) (end of shift, end ofworkweek)

hour) 0 - 31 ug/dLead per gm ofCreatinineNo referenceinterval (ug/g CRT)

Cadmium, Urine0.0-2.6 ug/LCadmium, Urine(24-hour) 0.0-3.3ug/dCadmium pergram of creatinine0.0-3.0 ug/g crt

Mercury, Urine =0-10 ug/LMercury, Urine(24-Hour) = 0-15ug/d

Mercury per gramof creatinine = Noreference interval(ug/g CRT)

Urine (24 hr.)CBCHair Fingernail

Urine (24hr.)Scalp hair

1035

BAT (Biological ToleranceValue) 50 ng/ml (metallic andinorganic)BAT (Biological ToleranceValue): 100 ng/ml (organic)

References

1. Harrison’s Principle of Internal Medicine 15th Edition page No.2590 –2595

2. http://www.medicine.uiowa.edu/Path_Handbook/indices/B.html

1036

ANNEXURE-II

LEAD

Lead is number 2 on the ATSDR’s “Top 20 List.”

Source: Every year, industry produces about 2.5 million tons of lead throughout the world. Mostof this lead is used for batteries. The remainder is used for cable coverings, plumbing, ammunition,and fuel additives. Other uses are as paint pigments and in PVC plastics, x-ray shielding, crystalglass production, pencils, and pesticides.

The inorganic forms of lead are absorbed through ingestion or inhalation, whereas organic lead saltsare absorbed through the skin. Only about 10% of an ingested dose is absorbed in adults, but theabsorbed percentage may be much greater in children. Lead absorption is enhanced bydeficiencies of iron, calcium, and zinc.

Targeted organs: Bones, Brain, Blood, kidneys, and thyroid gland (International OccupationalSafety and Health Information Centre 1999; ATSDR ToxFAQs for Lead).

Half Life: Some authorities list the half-life of lead in the bone as long as 30 years, while othersestimate the lead half-life in bone to be 105 days. Generally, excretion of lead is slow, with anestimated biologic half-life in soft tissues of 24-40 days. The remainder of the stored lead is foundin soft tissue, notably the kidney and brain.

Excretion: The primary route of excretion is through feces (80-90%). To a lesser extent, lead isexcreted in urine (10%). Lead passes the placental barrier and is found in breast milk.

Clinical Features – A patient with lead poisoning may have a combination of symptoms - or nosymptoms at all until the condition has progressed.

Acute Poisoning

Alimentary System - Thirst

Metallic taste in mouth

Nausea

Colic (Abdominal pain)

Diarrhoea

Loss of appetite (Anorexia)

CNS Parasthesia (numbness) Hallucination

Muscle pain Vertigo

Fatigue Lethargy

Convulsions Ataxia

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Slurred speech Sleeplessness

Loss of consciousness

CVS Hypotension / Hypertension

Circulatory collapse

Blood Pallor (Severe Anemia – acute hemolytic crisis)

Renal System Oliguria

Chronic Poisoning

Births defects Shaky hand Numbness

Mental Retardation Muscular weakness lack of concentration

Autism Paralysis (Beginning in fore arms) Psychosis

Allergies Arthritis Colic

Dyslexia Hyper activity Weight loss

Mood swings Nausea

Leadline in gingival

Seizures

Chronic subclinical exposure to lead is associated

Interstitial nephritis,

Tubular damage

Hyperuricaemia

Oliguria (decline in GFR)

Chronic Renal Failure.

Blood lead levels in the range of 0.34 – 1.7 μmol/lit are associated with

• Increase in blood Pressure

• Decrease in creatinine clearance

• Decrements in cognitive performance

Laboratory Investigation -

1. Blood Test

(i) Blood Lead levels (N) blood level of lead < 1.9 μmol/L (40 μg/dl)

In children > 10 mcg/dl;

In Adults > 40 μ/dl are considered to be of concern

1038

(ii) Complete Blood Count (CBC) – (Normochromic, Normocytic anemia withBasophilic stipplings on red cells in lead poisoning)

(iii) Serum Creatinine level (Elevated in chronic lead poisoning)

2. Long bone X-ray (in Children) (May reveal bands that indicate the failure of the bone torebuild)

3. Measurement of lead in teeth

4. Levels of lead in Urine [ Random urine < 150 μg/g creatinine (Not provoked with achelator) ]

5. Levels of lead in Faeces

6. Nerve Conduction Time (To know nerve induced peripheral demyelination)

7. Bone Lead Levels- k- ray-Flourescence

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ARSENIC

ANNEXURE-III

Arsenic is the most common cause of acute heavy metal poisoning in adults and is number1 on the ATSDR’s “Top 20 List.

Sources: Sources of arsenic include

• Pesticides

• Herbicides

• Fungicides

• Wood preservatives

• Ceramic enamels

• Paints

• Tobacco (There may be as much as 6 micrograms per pack)

• Burning of Fossil fuels as arsenic is a contaminant

Occupational exposure can occur in

• The Smelting Industry (arsenic is a by –product of ores containing lead,gold,zinc,cobalt andnickel)

• The microelectronics Industry

• Coal Power Plants

• Jobs involving the manufacturing of glass and fireworks

• Jobs with contact with pesticides

• Jobs with contact with wood treated with arsenic as a preservative

Absorption – Absorbed through skin, lungs and GIT

Targeted Organ: Target organs are the blood, kidneys, and central nervous, digestive, and skinsystems.

After absorption of inorganic arsenic, the compound accumulates in the liver, spleen,kidneys, lungs and gastrointestinal tract. It is then rapidly cleared from these tissues but it leavesa residue in Keratin rich tissues such as skin, hair and nails.

Metabolism Inorganic compounds are absorbed more readily than organic 80% of this isingested through GIT.

Blood 24 hour liver, kidney, lung and spleen

2 weeks skin, hair & bone.

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Inorganic salts in - leukocytes

(x) (does not cross crosses placenta.

Blood brain barrier)

Excretion – 90 – 95% in Urine

5 – 10% in excreta

Small amounts are recovered in bile, feces & saliva,

After an overdose, arsenic may be detected in urine up to 7-21 days.

Lethal dose - 130-300 mg.

Toxicity - Acute toxicity of arsenic is associated with

GIT - Burning in throat

Difficulty in swallowing

Nausea

Vomiting

Diarrhoea

Abdominal Pain

Garlic odor in the breath.

CVS - Difficulty in breathing

Hypotension

Cyanosis

CNS - Delirium

Coma

Seizures

Urinary system- Acute Tubular Necrosis

Hemoglobinuria,/ Hematuria

Hematological System - Haemolysis

Eosinophilia

Bone Marrow Depression.

Chronic - 2-8 weeks following ingestion

Skin & Nails - Erythroderma

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Hyperkeratosis

Hyperpigmentation

Exfoliative Dermatitis

Aldrich Mees lines (Transverse white striae on the fingernails)

Mucous Membrane

• Laryngitis

• Tracheitis

• Bronchitis

CNS • Polyneuritis (sensory & Motor)

• Basal cell carcinomas

• Squamous cell carcinomas

Other effects • Capillary injury

Necrosis of stomach, small bowel, vascular & degenerative changes in liver& kidney

Laboratory Investigations-

Arsenic levels can be measured in blood, urine, hair and fingernails. Urine tests are most reliable

1. X-ray abdomen - (As is radio opaque and is seen on x-ray of abdomen).

2. ECG- (QRS complex broadening, QT prolongation, ST segment depression, T waveflattening & multifocal ventricular tachycardia)

3. LFT (abnormal)

4. Hb (anaemia)

5. Leukopenia/ Leukocytosis

6. Protein urea

7. Hematuria

8. Cellular casts in the urine

9. Urine Arsenic levels (normally less than 67 nmol 5 μg/d)

10. May also be detected in hairs & nails for months following exposure.

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ANNEXURE-IV

CADMIUM

Cadmium is a byproduct of the mining and smelting of lead and zinc and is number 7 onATSDR’s “Top 20 list.”

(Absorbed Cd is mostly concentrated in liver and kidneys)

Sources – Cadmium has a wide variety of sources in the environment and from industry. Onesource is from ingestion of grown foodstuffs, especially grain and leafy vegetables, which readilyabsorb cadmium from the soil. The cadmium may occur naturally or as a contaminant and thecontaminants include sewage, sludge fertilizers, polluted ground water and mining effluents.

Cadmium is also a constituent of alloys, pigments, batteries, metal coatings for example protectivecoating on steel, plastics and fertilizers. Occupational exposure may occur from the manufacture ofthese products and from welding, and smelting of lead, zinc and copper as these occur in mixedores with cadmium. Cadmium is also found in Cigarette fumes and fumes from vehicles.

Absorption: Inhalation accounts for 15-50% of absorption through the respiratory system; 2-7%of ingested cadmium is absorbed in the gastrointestinal system.

Target organs - Target organs are the liver, placenta, kidneys, lungs, brain, and bones (Roberts1999; ATSDR ToxFAQs for Cadmium).

Clinical Toxicology – (4-24 h)

Acute - High dose Cd inhalation can cause severe respiratory irritation.

Pleuritic chest pain

Dysponea

Cyanosis

Fever

Tachycardia

Nauses

Pulmonary edema (non cardiogenic)

COPD

Renal Disease

Fragile bones

Emphysema

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Through Ingestion (Acute)

Nauses

Vomiting

Salivation

Abdominal cramps

Diarrhoea

Chronic

Anosmia - Alopecia

Yellowing of the teeth - Anaemia

Emphysema - arthritis

Minor changes in the liver function - learning disorders

Micorocytic hypochronic anemia

(unresponsive to iron therapy) - migraines

Renal tubular dysfunction

(Proteinuria & increased excretion of B2 microglobulin) - growth impairment

Osteomalacia (bone lesions & Pseudofractures)

Osteoporosis, loss of taste & smell poor appetite

Lab. Findings.

1. Blood level of CD >500nmol/L (5 μg/dl) is considered toxic)

2. urinary conc of B2 microglobulin.

24 hour urine. Specimen →→→→→ Creatinine level in urine

CBC Hair & Fingernail clippings)

(Creatinine level in unine above 10 mg/dl) suggest Cadmium toxicity.

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ANNEXURE-V

MERCURY

Mercury is number 3 on ATSDR’s “Top 20 List”. It is generated naturally in the environment fromthe degassing of the earth’s crust, from volcanic emissions. It exists in three forms: elementalmercury and organic and inorganic mercury.

Sources : Mining operations, chloralkali plants, and paper industries are significant producers ofmercury (Goyer 1996).Mercury continues to be used in thermometers, thermostats, and dentalamalgam. (Many researchers suspect dental amalgam as being a possible source of mercurytoxicity [Omura et al. 1996; O’Brien 2001].) Medicines, such as mercurochrome andmerthiolate, are still available. Algaecides and childhood vaccines are also potential sources. Peoplewho consume more than two fish meals a week are showing very high serum levels of mercury.

Absorption: Inhalation is the most frequent cause of exposure to mercury. The organic form isreadily absorbed in the gastrointestinal tract (90-100%); lesser but still significant amounts ofinorganic mercury are absorbed in the gastrointestinal tract (7-15%). Target organs are the brainand kidneys (Roberts 1999; ATSDR ToxFAQs for Mercury).

Target Organs: Target organs are the brain and kidneys (Roberts 1999; ATSDR ToxFAQs forMercury).

Symptoms:

Symptoms of acute exposure are

• Cough

• Sore throat

• Shortness of breath

• Metallic taste in the mouth

• Abdominal pain

• Nausea,

• Vomiting

• Diarrhoea

• Headache

• Weakness

• Visual disturbances

• Tachycardia

• Hypertension.

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Chronic exposure to mercury may result in

• Permanent damage to the central nervous system (Ewan et al. 1996) and kidneys.

• Tremors

• Anxiety

• Forgetfulness

• Emotional instability

• Insomnia

• Fatigue

• Weakness

• Anorexia

• Loss of Cognitive functions

• Mercury can also cross the placenta from the mother to the fetus (levels in the fetus areoften double those in the mother) and accumulate, resulting in mental retardation, braindamage, cerebral palsy, blindness, seizures, and inability to speak

Laboratory Investigations:

• Blood and urine samples are used to determine recent exposure, as well as exposure toelemental mercury and inorganic forms of mercury.

• Blood mercury levels should not exceed 50 mcg/L (see the ATSDR MedicalManagement Guidelines).

• A 24-hour urine specimen is collected for measurement of mercury levels.

• Chest x-rays can reveal a collection of mercury from exposure to elemental mercury ora pulmonary embolism containing mercury (Ferner 2001).

• Abdominal x-rays can reveal swallowed mercury as it moves through the gastrointestinaltract.

• Scalp hair is used in testing for exposure to methylmercury.

• Liver and kidney function tests are also important in severely exposed persons.

References

Harrison’s Principle of Internal Medicine 15th Edition page No.2590 –2595

MetalsasToxins:http://www.portfolio.mvm.ed.ac.uk/studentwebs/session2/group29/introtox.htmhttp://www.medicine.uiowa.edu/Path_Handbook/indices/B.html http://www.lef.org/protocols/prtcl-072.shtml#mostimpblt

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Drug: Study Code:


OPEN OBSERVATIONAL STUDY ON CLINICALSAFETY OF SELECTED AYURVEDIC AND SIDDHA



1048

Blank

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I. BACKGROUND

The use of metals in therapeutic drugs has become increasingly important over the lastcouple of decades; Ayurveda recognizes their use long before that. Rasashastra, one among thesubspecialties of Ayurvedic Pharmaceuticals and Siddha classics have specified therapeutic use ofmetals and minerals in the form of Bhasmas and Rasakalpas. As these drugs required in lesserdoses, causes no distaste unlike herbal drugs and faster in action, these practices became popularand widely accepted and safely used since long.1

Heavy metals are chemical elements with a specific gravity that is at least 5 times thespecific gravity of water. There are 35 metals that concern us because of occupational orresidential exposure; 23 of these are the heavy elements or “heavy metals”: antimony, arsenic,bismuth, cadmium, cerium, chromium, cobalt, copper, gallium, gold, iron, lead, manganese, mercury,nickel, platinum, silver, tellurium, thallium, tin, uranium, vanadium, and zinc (Glanze 1996).Interestingly, small amounts of these elements are common in our environment and diet and areactually necessary for good health, but inappropriate dosage forms of any of them may causeacute or chronic toxicity (poisoning).

Some well-known toxic metallic elements with a specific gravity that is 5 or more timesthat of water are Arsenic, 5.7; Cadmium, 8.65; Iron, 7.9; Lead, 11.34; and Mercury, 13.546(Lide 1992).2

Articles ( JAMA, Dec.15, 2004, Vol.292, No.23) published in some journals havementioned about the toxicity, presence of heavy metal contents of certain Ayurvedic Classical/Proprietary preparations which is creating misconceptions among scientific communities and generalpublic regarding the safety of Ayurvedic/Siddha Rasa Kalpas and Bhasmas.


OPEN OBSERVATIONAL STUDY ON CLINICAL SAFETY OF SELECTED(VASANTA KUSUMAKARA RASA) AYURVEDIC AND SIDDHA


References

1. RasaRatna Samuchchaya, chapter 28/1.

2. http://www.lef.org/protocols/: Heavy Metal Toxicity

3. RasaRatna Samuchchaya, chapter 5/11,20,30,147.

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The classics of Ayurvedic Rasashastra and siddha system have specified differentmethods of preparation and operational procedures since from the collection of raw drugs theirpurification, processing, method of use, dosage forms etc. The raw drugs and finished products, ifnot processed and preserved as per the classical literature specified, they may lead to improperfinished product with contaminants and may lead to toxic symptoms3. Thus this project isundertaken to assess the heavy metal toxicity in patients receiving Ayurvedic /siddha preparations.

II. OBJECTIVES:

Observe the clinical/biochemical changes in subjects receiving Vasanta Kusumakara Rasa- an Ayurvedic Herbomineral / Metallic preparations for ensuring Clinical safety

III. CENTRE: Identified CCRAS Institutes.

IV. SOURCE OF PROCUREMENT OF TRIAL DRUGS:

The selected Ayurvedic & Siddha drugs will be procured from IMPCL and IMPCOPS,Chennai. The requisite quantities of all the drugs will be procured and supplied to the identifiedInstitutes and CSMDRIA, Chennai by Central Research Institute (Ay) New Delhi [from IMPCL],Central Research Institute (Siddha), Chennai [from IMPCOPS]. The physico-chemical standardswill be evolved by Cpt. Srinivasa Murthy Drug Research Institute for Ayurveda, Chennai.

V. SAMPLE SIZE AND METHODS: - 15 subjects

TYPE OF STUDY : Open

LEVEL OF STUDY : OPD

PERIOD OF TREATMENT : 30 days

PERIOD OF STUDY : 6 months

DRUG & Details of treatment schedule

a) Drug- Vasanta Kusumakara Rasa

b) Diagnosis - Prameha, Dourbalya

c) Dosage schedule and duration - 60 mg BD for 30 days

d) Combinations with the main drug: Vasanta Kusumakara Rasa 60 mg. in 3 gms. ofAshwagandha Churna.

e) Anupana [Vehicle]: Water.

VI. CRITERIA FOR INCLUSION:

1. Patients above 20 years and below 60 years of age.

2. Biochemical investigations for heavy metals at 0 day of assessment within the range.

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3. Clinically diagnosed cases of Prameha & Dourbalya

VII. CRITERIA FOR EXCLUSION:

1. Serum metallic levels of any of the metals exceeding permissible range at day 0 ofassessment

2. Age below 20 years & above 60 years

3. Known renal or Hepatic Pathology (Confirm by Clinical/Biochemical parameters)



6. Major neuro-Psychiatric abnormalities

7. Chronic Smokers/Tobacco consumers

VIII. CRITERIA FOR WITHDRAWAL:



Screening of the patients will be recorded as per case record form-I. The full details ofhistory and physical examination of the subjects will be recorded as per case record forms (Caserecord form II). Clinical and physiological assessment (Case record form -III) and laboratoryinvestigations (Case report form -IV3) will be done before treatment, at 0, 15th & 30th days.


Data on clinical symptoms and objective tests before and after the treatment will betabulated and analyzed using appropriate statistical tools. The data generated at the Institute on theselected trial drug will have to be communicated to the Statistical Officer of CCRAS from time totime through e-mail.

XI. CRITERIA FOR ASSESSMENT OF OUTCOME OF STUDY

The assessment of progress & outcome of the study are assessed on the basis of clinicaland biochemical investigations.

XII. TRIAL MONITORING AND DATA ANALYSES

The Statistical Section, CCRAS, Hqrs, New Delhi will undertake the monitoring ofprogress of the trial and data analysis.

1052


Institutional Ethical Committee (IEC) of participating Center’s shall issue clearancecertificate before the project is initiated. Patient’s information sheet and informed consent form shallbe submitted along with project proposal for approval by IEC and maintained in duplicate with onecopy given to the patient at the time of entry to the trial.

XIV. TRAVELLING EXPENSES

A consolidated amount of Rs.100/- per visit (Total Rs.300/-) will be paid to the patient atthe end of the study.

XV. TRAINING TO INVESTIGATORS AND PERSONS INVOLVED

Short-term two-day training will be provided to the Investigators and Laboratorypersonnel involved in this open observational trial at CCRAS Hqrs. and Central Research Institute(Ay.), New Delhi. The investigators and technicians will be detailed about the clinical trial conductand laboratory procedures in order to maintain the uniformity.

XVI. LABORATORY INVESTIGATIONS


XVII. FINANCIAL APPROVAL:

The financial implications as required for different purposes will be met from sanctionedbudget of the Institute concerned under the head Research Activities (Plan). All the proceduresshould be executed following the codal formalities with necessary approvals of the Council.

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Name: ____________________________

CONSENT BY SUBJECT

I have been informed to my satisfaction, by the attending physician, the purpose of the trialand the nature of drug treatment and follow-up, including the laboratory investigations to beperformed to monitor and safeguard my body functions.


I, exercising my free power of choice, hereby give my consent to be included as a subjectin the clinical trial on “Open Observational Study on Clinical Safety of Selected (VasantaKusumakara Rasa) Ayurvedic / Siddha Herbomineral and Metallic Preparations.”





Relationship ___________________________________


1054


OPEN OBSERVATIONAL STUDY ON CLINICAL SAFETY OF SELECTED(VASANTA KUSUMAKARA RASA) AYURVEDIC AND SIDDHA HERBOMINERAL

AND METALLIC PREPARATIONS.



The use of metals in therapeutic drugs has become increasingly important over the lastcouple of decades; Ayurveda & Siddha recognizes their use long before that. The AyurvedicRasashastra, one among the subspecialties of Ayurvedic & Siddha Pharmaceuticals has specifiedtherapeutic use of metals and minerals in the form of Bhasmas and Rasakalpas. As these drugsrequired in lesser doses, causes no distaste unlike herbal drugs and faster in action, these practicesbecame popular and widely accepted and safely used since long.

The Ayurvedic preparation- Vasantha kusumakara ras, identified for the observational studyis being frequently prescribed by the practitioners since time immemorial for various commonailments encountered in the general practice and found safe and effective.

However, considering the eco- climatic changes traces of certain unwanted substances maylead to untoward effects. Thus this project is undertaken to assess the clinical safety in subjectsreceiving Ayurvedic preparations.


Your doctor will explain clearly what you have to do. It is important that you follow theinstructions scrupulously. The study will take approximately 1 month to complete. During thisperiod, you are expected to visit the hospital 3 times (0, 15th & 30th days) for clinical,biochemical and physiological assessment.

Before you start treatment, during the first visit to the clinic, you will undergo a completephysical examination, required objective tests and laboratory investigations will also be done. If youare found eligible, you would be put on treatment for 1 month.



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HERBOMINERAL AND METALLIC PREPARATIONS.


BEFORE TREATMENT

(Enter a (�) in the appropriate box)

1. Centre: ………………..……….





6. Address Permanent postal address with phone number & email if any.

..............................................................................................................................

..............................................................................................................................


1. Age above 20 & below 60 years

2. Biochemical investigations for heavy metals at0 day of assessment within the range.

3. Clinically diagnosed cases of Prameha & Dourbalya

EXCLUSION CRITERIA Yes (1) No (0)

4. Serum metallic levels of any of the metals Exceeding permissible range at day 0 of assessment

5. Age below 20 & Above 60 years

6. Known Renal or Hepatic Pathology

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9. Major neuro- Psychiatric abnormalities

10. Chronic Smokers / Tobacco Consumers.

A patient is eligible for admission to the trial, only if sl. No.1 - 3 are “yes” & if the sl.No. 4-10 are “no”.

Date:___________________ Signature of Doctor:______________________

1057





1. Centre: ………………..……….






7. Address Permanent postal address with phone nu,ber & email if any.

8. Educational status: Illiterate 1 Literate 2 Matriculation 3

Graduate 4 PG 5

9. Annual Income Rs.

Less than Rs. 60,000/- (1) More than Rs. 60,000/- (2)

10. Occupation:

A. Current occupation related to significant exposure of dust, chemical, smoke orheavy metal.

Yes If yes, details

No __________

B. Previous Occupation: [in last 3 years]

Was there any significant exposure to dust, chemicals smoke or heavy metal

Yes If yes, details

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No __________


a. H/o of intake of any Ayurvedic medicine yes-1 No-2for the past 3 months

b. Disease/Cause for which therapy was taken —————————————————

c. Name of the Drug 1. —————————————————————

(Including brand name, 2. —————————————————————

Pharmacy, Batch no. & 3. —————————————————————

Dosage) 4. —————————————————————

5. —————————————————————

d. Date of starting the treatment: ——————————————————————

e. Duration of treatment ——————————————————————

f. Date of termination of therapy: ——————————————————————

g. Reason for termination of Therapy: ————————————————————

h. Cured / Dropped Out etc. ———————————————————————

12. History of Past illness:

Yes-1 No-2

If yes, details…………………………………………….....................................................


2. Previous episode


4. Treatment given so far

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13. Personal History:

Diet Veg (1) Non-veg. (2)

Sleep Satisfactory: (1) Unsatisfactory (2)

Constipation Yes (1) No (2)

History of Environmental tobacco

Smoking exposure Yes No Duration

Tobacco chewing

Betel chewing

History of alcohol intake

Occasional (1) Regular (2)

Prakriti


Vata-kaphaj 4 Vata-pittaj 5 Pitta-kaphaj 6

Sama 7


Chief complaints & Duration

DIAGNOSIS:

OTHER SPECIFIC SYMPTOMS IF ANY WITH DURATION (0, 15th & 30thday)

Present-1 Absent-2 If present thenduration in months


2. Cough (Hg)



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7. Thirst (Pb)



10. Abdominal Pain (As,Cd,Hg, Pb)


12. Metallic taste in mouth (Hg, Pb)

13. Difficulty in breathing (As, Cd, Hg)

14. Chest Pain (Cd)







21. Loss of Appetite-Anorexia (Pb, As, Hg)

22. Fever (As,Cd)






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29. Anxiety (Hg)


31. Insomnia (Hg)



34. Numbness (Pb)

35. Vertigo (Pb)



Note. Similar Signs/symptoms appearing as result of disease process /previous treatmentshould be noted separately to avoid misinterpretation.


Height (cm) ________________

Weight (kg) ________________

________________

Pulse (per min) ________________

Respiration rate (per min) ________________

Blood Pressure (mm Hg) ________________

Systolic ________________

Diastolic ________________

Body temperature ( o F) ________________


Height (meters)2{ }

1062


Pallor

Lymphadenopathy

Cyanosis (As)

Clubbing nails

Edema

If present, specify General (1) Local (2)

Area __________________________________________________________________

Bluish line on Gingiva (lead line)

Skin & nails

Erythroderma (As)

Hyperkeratosis (As)

Hyperpigmentation (As)

Exfoliative Dermatitis (As)

Aldrich Mees Lines (As) (Transverse white striae on fingernails)


CVS


CNS


Respiratory system

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Digestive system


Urogenital system



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CASE REPORT FORM III– CLINICAL AND PHYSIOLOGICAL ASSESSMENT

(0, 15th, 30thday)

1. Centre: ………………..……….






7. Contact no. (Permanent postal address and phone number)

..............................................................................................................................Email ID ..............................................................................................................


9. Name of Formulation ...........................................................................................................

ASSESSMENT OF THE TREATING CONDITION (The investigator should record theprogress of the treating condition viz. Improvement, adverse effects etc.)

OTHER SPECIFIC SYMPTOMS WITH DURATION (IF ANY)

Present-1 Absent-2 Duration


2. Cough (Hg)



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7. Thirst (Pb)



10. Abdominal Pain (As,Cd,Hg, Pb)


12. Metallic taste in mouth (Hg,Pb)

13. Difficulty in breathing (As,Cd,Hg )

14. Chest Pain (Cd)







21. Loss of Appetite-Anorexia (Pb,As,Hg)

22. Fever (As,Cd)






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29. Anxiety (Hg)


31. Insomnia (Hg)



34. Numbness (Pb)

35. Vertigo (Pb)




38. Height (cm) ________________

39. Weight (kg) ________________

40. ________________

41. Pulse (per min) ________________

42. Respiration rate (per min) ________________

43. Blood Pressure (mm Hg) ________________

44. Systolic ________________

45. Diastolic ________________

46. Body temperature ( o F) ________________


47. Pallor

48. Lymphadenopathy


Height (meters)2{ }

1067

49. Cyanosis (As)

50. Clubbing nails

51. Edema

If present, specify General Local (Area) _________________

52. Bluish line on Gingiva (lead line)

Skin & nails

53. Erythroderma (As)

54. Hyperkeratosis (As)

55. Hyperpigmentation (As)

56. Exfoliative Dermatitis (As)

57. Aldrich Mees Lines (As) (Transverse white striae on fingernails)


CVS


CNS


Respiratory system


Digestive system





1068





(0, 15th, 30th days)

1. Centre: ………………..……….







Urine Examination

8. Routine____________ Microscopic___________

9. Urinary levels of heavy Metals As ___________

Pb___________

Cd___________

Hg___________

Haematological Investigations

10. Serum Analysis for heavy Metals: As ___________

Pb ___________

Cd ___________

Hg ___________

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11. Hb (g/dl) _______________________________

12. TLC (Cells/Cu.mm.) ______________________

DLC

13. P (%) __________________

14. L(%) __________________

15. M (%) __________________

16. E(%) __________________

17. B (%) __________________

18. ESR (1st hour.) (mm) __________________

Blood Sugar

19. Fasting (mg./dl) __________________

20. Uric acid (mg./dl) __________________

Kidney function tests (Sl.No.)

21. B.Urea (mg./dl) __________________

22. S.Creatinine (mg./dl) __________________

Liver function tests (Sl.No.)

23. Total proteins (g./dl) __________________

24. Albumin (g. /dl) __________________

25. Globulin (g. /dl) __________________

26. A/G Ratio __________________

27. S.Bilirubin(mg./dL)

a. Total __________________

b. Direct __________________

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c. Indirect __________________

d. SGPT. (IU/L) __________________

e. SGOT (IU/L) __________________

28. Alk. Phosphates (KA units) __________________

29. X-ray chest (PA View) _____________________________________________

30. USG Whole Abdomen _____________________________________________

_____________________________________________

31. ECG (0,12 WEEK& if symptoms suggest sos) _________________________________


Date:______________ Signature of the Research Fellow/Investigator _______________

Place:_____________

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ANNEXURE

SEC

TIO

N-X

IX

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1073

1. PHYSIOLOGICAL STATUS (PHS)

1.01 Status of Appetite: (AD)

a. Good appetite

b. Stable appetite with usually moderate desire to eat

c. Variable appetite

1.02 Dietary/Eating habits (DH)

a. Enjoys eating, ready to eat mostly & hates to miss food

b. Regular food habits, but can spend hours without food

c. Desirous to take food, eats less at a time, needs mid-mealssnacks

1.03 Bowel Habits (BH)

a. Regular, once-a-day, stool well formed, if constipated it is mild(Respond to medium strength laxative)

b. Regular & frequent, stool semisolid or loose, rarely constipated.(Respond to mild laxatives sometimes even milk, fig., raisins etc.)

c. Variation seen, mostly constipated (strong purgatives are needed)

1.04 Sleeping Pattern (SH)

a. Sleeps easily but light

b. Sleeps easily and sound (heavily)

c. Trouble to get sleep, light sleep / Variable sleep pattern

1.05 Morning feelings, after leaving the bed (MF)

a. Don’t feel fresh

Annexure-I



CASE REPORT FORM FOR DETERMINATION OF PRAKRITI /UDALIYAL/MIZAJ

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b. Feel fresh. Feel well even with less sleep.

c. Feel fresh but not good when have less hours of sleep.

1.06 Dreams (DM)

a. Cool and peaceful dreams, not bothers to remember

b. Passionate dreams, sees heat, light & remembers well

c. Plenty of dreams, mostly related to motion, usually forgets

1.07 Physical working capacity/physical strength

a. Starts with speed & gets exhausted easily

b. Loves hard work, has moderate capacity

c. Good stamina but slow and not interested for physical work.

1.08 Performance of activities

a. Quickly with a lot of initiative

b. Moderately with medium initiative

c. Slow, steady and balance activities

1.09 Talking

a. Very fast missing words

b. Sharp, provocative and clear-cut

c. Slow, clear and stable

1.10 Walking

a. Very quick with swift movement

b. Normal and rhythm

c. Slow and steady

1.11 Associated movements of body while working

a. Excessive and frequent, difficult to tolerate

b. Less thirst, easy to tolerate

c. Moderate perspiration, consistent to climate, with pleasant smell.

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1.12 Nature of Thirst (TN)

a. Excessive and frequent, difficult to tolerate

b. Less thirst, easy to tolerate

c. Moderate and variable thirst

1.13 Status of Perspiration (SP)

a. Scanty even in hot climate but odourless

b. Profuse with strong odour

c. Moderate perspiration, consistent to climate, with pleasant smell.

1.14 Sexual qualities (SQ)

a. Variable, strong desire, overindulgence, & gets exhausted

b. Moderate with domina ting behavior

c. Usually low and steady desire, with good stamina

1.15 Quantity of seminal discharge

a. Scanty and comparatively thin in consistency

b. Moderate and normal

c. Plenty and thick

1.16 Fertility or productivity

a. Comparatively lesser

b. Less

c. Capable of producing good no. of off springs

1.17 Longevity or average age

a. Short life span

b. Moderate life span

c. Long life span

1.18 Resistance to diseases (RD)

a. Usually poor. Frequently fall ill.

b. Medium

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c. Good. Able to tolerate seasonal variation, food etc. well

1.19 Climatic Preferences (CP)

a. Prefers warm, avoids cold climate

b. Likes cold, but intolerant to warm/hot

c. Likes normal climate & prefers warm in comparison to cold

2. MENTAL/PSYCHOLOGICAL STATUS:

2.01 Mental Reactions (MR)/Personality Traits:

a. Very sensitive, reacts quickly

b. Gets Irritated easily & sustains it.

c. Cool, calm, avoids confrontations

2.02 Memory Status (MS)

a. Remembers easily & tends to forget easily

b. Takes time to grasp, but retains for long

c. Remembers easily and tends to retain

2.03 Leadership quality (LQ)

a. Don’t like to lead and happy as a follower.

b. Requires commanding status.

c. Avoid leading.

2.04 Decision making capacity(DMC)

a. Takes immediate decision without thinking much.

b. Takes decision after properly analyzing the facts.

c. Avoid taking decision. Usually keeps them pending.

2.05 Concentration Power (CP)

a. Very easy to concentrate on a work, but not for long duration

b. Difficult to concentrate on a work

c. Retains concentration for a long period

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2.06 Attitude towards problems or difficulties

Lot of worrying, instability in reaction

Angry, over awed, easily provoked and highly irritable

Peaceful, slow, steady and balance

2.07 Nature

a. Easily irritable, irritating to others, exaggerating, anxious materialistic liking

b. Polite but hot-tempered, proudy, brave, bold, less but good friendship

c. Polite, decent, not greedy, appreciating, have good and long lasting friendship

2.08 Liking about taste (TL)

a. Sweet, salt & sour

b. Sweet, bitter & astringent

c. Pungent, astringent & bitter

3. PHYSICAL FEATURES: (PF)

3.01 Body frame (BF)

a. Thin body frame, unusually long/short

b. Medium frame

c. Broad, Large frame

3.02 Body weight (BW)

a. Moderate/Average weight

b. Underweight or Tendency of fluctuation

c. Over weight or with a tendency to gain weight

3.03 Distribution of body fat (DBF)

a. Unequal/on specific areas

b. Evenly distribution

c. Scanty deposition of body fat.

3.04 Nature/Texture of skin

a. Delicate, Irritable skin, gets wrinkles easily

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b. Dry, rough, cracked, or having a tendency of cracking

c. Smooth, firm, soft, clear with good lusture, not prone to disorders

3.05 Complexion/skin color (SC)

a. Extremely fair / pinkish

b. Fair, reddish, burns easily

c. Comparatively dull or darkish, tans easily

3.06 Body Hair (BH)

a. Dry, rough, coarse, lustureless & curly

b. Soft, scanty, straight, fine textured

c. Thick, shiny, moderate

3.07 Forehead (FH)

a. Large

b. Medium

c. Small

3.08 Eyes (EF)

a. Rolling, restless, small, dull & lusterless

b. Sharp, medium sized with sclera of reddish tinge

c. Large calm stable eyes with milky white sclera

3.09 Teeth (TE)

a. Teeth are of average size, yellowish, prone to cavities

b. Dry, cracked, irregular dull white

c. Large, even, gleaming white

3.10 Tongue (TO)

a. Thin tongue, with blackish spots, often coated with thin adherent coating

b. Medium, Reddish, occasionally coated with yellow or red coating

c. Thick usually clear, rarely coated, coating is usually thick white

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3.11 Lips (LP)

a. Soft, moist & reddish

b. Dry, thin & blackish

c. Thick & glossy

3.12 Blood Vessels (BV)

a. Prominent

b. Less prominent

c. Not visible

3.13 Scalp Hair (SH)

a. Dark in Shade, coarse, rough, easily prone to dandruff and split ends.

b. Thin, delicate, straight, light coloured, turn grey at an early age

c. Strong, thick, dark, slightly wavy with good lusture, oiliness is usuallyone of the chief complaints

3.14 Joints (JT)

a. Crackling joints, hyper mobile in nature

b. Comparatively normal but have soft and loose ligaments

c. Well lubricated, strongly built joints which are well organized, well covered

3.15 Voice (VR)

a. Rough, unclear voice, which turns hoarse or cracks on strain

b. Concise, sharp voice, intense in nature & high pitched

c. Deep, pleasant, resonant voice which is melodious, resonating,but lower in pitch and intensity

3.16 Nail (NL)

a. Hard, brittle, rough & differ in size from one another, bluish/grayish incontour

b. Soft, Strong, well formed, Lustrous, pink in colour

c. Strong, large, thick symmetrical & somewhat pale in colour

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3.17 Body temperature

a. Feels slightly cold on touch

b. Feels slightly warm on touch

c. Normal

3.18 Shape of Palms and feet

a. Short and broad

b. Medium and slim

c. Long and broad

3.19 Face

a. Small and broad with uneven features

b. Medium & oval with sharply defined features

c. Round, babbly and attractive with balance features

4 Social or economical status

4.01 Economy

a. Getting less outcome with hard work

b. Getting good outcome with moderate efforts

c. Enjoys lavishly and royal life

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SCORE SHEET FOR DETERMINATION OF PRAKRITI /UDALIYAL /MIZAJ

Sl. no. of the subject_________________________________________________________

S.No. Observation Options Identified Area (V/P/K)Code a b c

1. 1.01 P K V

2. 1.02 P K V

3. 1.03 K P V

4. 1.04 P K V

5. 1.05 V P K

6. 1.06 K P V

7. 1.07 V P K

8. 1.08 V P K

9. 1.09 V P K

10. 1.10 V P K

11. 1.11 V P K

12. 1.12 P K V

13. 1.13 V P K

14. 1.14 V P K

15. 1.15 V P K

16. 1.16 V P K

17. 1.17 V P K

18. 1.18 V P K

19. 1.19 V P K

20. 2.01 V P K

21. 2.02 V K P

22. 2.03 K P V

23. 2.04 V P K

24. 2.05 P V K

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25. 2.06 V P K

26. 2.07 V P K

27. 2.08 V P K

28. 3.01 V P K

29. 3.02 P V K

30. 3.03 K P V

31. 3.04 P V K

32. 3.05 K P V

33. 3.06 V P K

34. 3.07 K P V

35. 3.08 V P K

36. 3.09 P V K

37. 3.10 V P K

38. 3.11 P V K

39. 3.12 V P K

40. 3.13 V P K

41. 3.14 V P K

42. 3.15 V P K

43. 3.16 V P K

44. 3.17 V P K

45. 3.18 V P K

46. 3.19 V P K

47. 4.01 V P K

INDIVIDUAL SCORE OF VPK V P K

PERCENTAGE OF VPK V= P= K=

TYPE OF PRAKRITI /UDALIYAL/ MIZAJ

Abbreviations-V- Vata /Vali/Sauda, P- Pitta /Azhal/Safra, K- Kapha/ Iyam/Balgam

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To draft a sound scientific design of a clinical research study, the medical writer at the TGH, officeof Clinical Research recommends that the following information should be included in aresearch protocol. It will help facilitate the application submission process and study approval fromthe office of Clinical Research and IRB.

Study Summary:

Study summary should include the following:

• Protocol title (The title on related IRB submissions (e.g., applications for new study,changes in procedure, research progress reports) must match the title of the protocol)

• Study phase

• Duration of the study

• Methodology

• Study site

• Approximate number of subjects

• Name, title, address, and telephone number of the PI, Co-PI, sponsors and studycoordinators

• Investigator’s affiliation

List of Abbreviations:

Provide a list of abbreviation used in the study protocol.

Annexure-II

GUIDELINES FOR DESIGNING A CLINICAL STUDY PROTOCOL

(based on International Conference on Harmonization, GCP Guidelines forClinical Trial Protocol development)

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Background Information/Significance:

• Name and description of the investigational product, and in case of retrospective reviews,justification for the chart and medical record reviews.

• Summary of results from prior clinical studies and clinical data to date.

• Human subjects risks and benefits.

• Description of the population to be studied.

• Description and justification for the dosing regimen and treatment period.

• A paragraph stating that the clinical study will be conducted in compliance with theprotocol, SOPs and the federal, state and local regulations.

• Citations from the references and data relevant to the study that also provides backgroundfor the trial.

Objectives/Rationale/Research Question:

• Include a detailed description of the primary and secondary objectives and the purpose ofthe study and clearly state your research hypothesis or your question.

• Discuss the project’s feasibility.

• Give details of resources, skills and experience to complete the study.

• Include any pilot study information.

Clinical Study Design:

• Primary and secondary endpoints, if any, to be measured during the study.

• Include the information that is needed to answer the research question.

• Include the study design e.g. single, double-blind, observational, randomized, retrospectiveetc. A schematic diagram of the study design would be helpful.

• Include the amount of dosage, dosing regimen of the drug, packaging and labeling of theexperimental drug.

• Explain how the study drug will be stored and dispensed.

• Include the expected duration of the study and subject’s participation and a description ofthe sequence and duration of all study periods.

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• Include any follow up visits.

• Describe when a subject’s participation in the trial may be discontinued.

• Maintenance of randomization codes and confidentiality.

• Describe the potential risks and steps taken to minimize the risks.

• Identify possible benefits of the study.

Inclusion and Exclusion criteria of the Subjects:

• Include subjects inclusion criteria.

• Include subjects exclusion criteria. Women of childbearing potential may not be routinelyexcluded from participating in research, however, pregnant women should be excludedunless there is a clear justification to include them.

• Include enrollment of persons of diverse racial and ethnic backgrounds to ensure that thebenefits of the research study are distributed in an equitable manner.

Informed consent form process:

• Provide information about the regulatory requirements of the consent form and whichlanguages will be used.

• Include a discussion of additional safeguards taken if potentially vulnerable subjects will beenrolled in the study e.g., children, prisoners, cognitively impaired and critically ill subjects.

• Specify Code of Ethics under which consent will be obtained.

• Include a copy of the proposed informed consent along with the protocol.

Adverse Event Reporting:

• Describe your plan to report any adverse event.

• Anticipated adverse events should be clearly documented.

• Identify the type and duration of follow up and treatment for subjects that experience anadverse event.

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Assessment of Safety and Efficacy:

• Be specific about the efficacy parameters.

• Include the methods and timing for assessing, recording and analyzing efficacy parameters.

• Specify the safety parameters.

• Record and report properly all the adverse events and inter current illnesses.

Treatment of Subjects:

• List all the treatments to be administered including product’s name, dose, route ofadministration and the treatment period for subjects.

• Include all medication permitted before and during the clinical trial.

• Include the procedures for monitoring subject compliance.

Data Collection Plan:

• Define the type of data collection instrument that will be used and list all the variables.

• Specify if computerized databases will be used.

• Identify what software will be used.

• Explain precautionary steps taken to secure the data.

Data Access:

• Inform who will have access to the data and how the data will be used. If data withsubject identifiers will be released, specify the person (s) or agency to whom theinformation will be released and the purpose of the release.

• Address all study related monitoring, audits and regulatory inspections.

Statistical Methods:

• Describe the statistical methods in detail.

• Include the number of subjects you are planning to enroll. For multi-center studies, includethe total number of sites expected and the total number of subjects to be enrolled acrossall sites.

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• Provide the rationale for the sample size, the calculations on the power of the trial and theclinical justification.

• Procedure of accounting for missing, unused and spurious data.

• Procedures for reporting deviations from the original statistical plan.

• Include the selections of subjects to be included in the analyses.

Conflict of Interest:

Identify and document clearly any consultative relationship that the principal or coinvestigators haswith a non-USF entity related to the protocol that might be considered a real or apparent conflictof interest.

Publication and Presentation Plans:

List any meetings or conference you will be presenting the data and the results of your study.

Timeline:

• A short paragraph stating when you plan to start and complete the study.

• Include a description e.g. subjects enrollment within a month, data collection within 6months etc.

References:

List all the references used in the background section at the end of the protocol.

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Blank

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Annexure-III


Essential information for prospective research on subjects: Before requesting an individual’sconsent to participate in research, the investigator must provide the individual with the followinginformation in the language he or she is able to understand which should not only be scientificallyaccurate but should also be sensitive to their social and cultural context:

Study Title:

Study Doctor:

Sites of Investigation:

Emergency Contact Details:

i. The aims and methods of the research (Purpose of the study).

ii. The expected duration of the research (brief description of the study and studyprocedures).

iii. The benefits that might reasonably be expected as an outcome of research to the subject orto others (Benefits to the patient).

iv. Any alternative procedures or courses of treatment that might be as advantageous to thesubject as the procedure or treatment to which she/he is being subjected (Discuss aboutalternative procedure or treatment).

v. Any foreseeable risk or discomfort to the subject resulting from participation in the study(Possible risks and side effects).

vi. Right to prevent use of his/her biological sample (DNA, cell-line, etc.) at any time during theconduct of the research (subject right).

vii. The extent to which confidentiality of records could be able to safeguard, confidentialityand the anticipated consequences of breach of confidentiality.

viii. Free treatment for research related injury by the investigator / institution.

ix. Compensation of subjects for disability or death resulting from such injury.

x. Freedom of individual / family to participate and to withdraw from research any timewithout penalty or loss of benefits which the subject would otherwise be entitled to.

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xi. The identity of the research teams and contact persons with address and phone numbers.

xii. Foreseeable extent of information on possible current and future uses of the biologicalmaterial and of the data to be generated from the research and if the material is likely tobe used for secondary purposes or would be shared with others, clear mention of the same.

xiii. Risk of discovery of biologically sensitive information.

xiv. Publication, if any, including photographs and pedigree charts.

CONSENT FORM

I ………………………………… exercising my free power of choice, hereby give my consentto be included as a subject in the clinical trial of a new drug, namely ………………………….for the treatment of ……………………….. . I understand that I may be treated with this drugfor the diseases. I am suffering from ………………………….. . I have been informed to mysatisfaction, by the attending physician the purpose of the clinical trial and the nature of drugtreatment and follow up including the laboratory investigation to monitor and safeguard my bodyfunction.

I am also aware of my right to opt out of the trial at any time during the course of the trial withouthaving to give the reasons for doing so.

Signature of the patient / legally acceptable Representative:

Date:

Signature of the attending physician / Investigator:

Date:

Signature of the impartial witness:

Date:

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