1. What data in particular will be shared?
   Response - All of the individual participant data collected during the trial, after de-identification.
   


2. What additional supporting information will be shared?
   Response -  Study Protocol
   Response -  Statistical Analysis Plan
   Response - Informed Consent Form
   Response - Clinical Study Report
   Response -  Analytic Code
   
   
3. Who will be able to view these files?
   Response - Anyone
   


4. For what types of analyses will this data be available?
   Response - To achieve aims in the approved proposal.
   


5. By what mechanism will data be made available?
   Response - Proposals should be directed to [nandinirdhinsi@gmail.com].
   


6. For how long will this data be available start date provided 20-05-2024 and end date provided 30-04-2025?
   Response - Immediately following publication. No end date.
   


7. Any URL or additional information regarding plan/policy for sharing IPD? 
   Additional Information - nil

RAJIV GANDHI UNIVESITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

COMPLETED PERFORMA FOR REGISTRATION OF SUBJECT (PANCHAKARMA) FOR THE DISSERTATION M.D. (AYURVEDA)

A RANDOMISED CONTROLLED TRAIL TO EVALUATE THE EFFICACY OF AYURVEDA INTERVENTION (NITYA VIRECHANA) AS AN ADD-ON TO STANDARD CARE IN SECONDARY HYPERLIPIDEMIA.

bY

dr. NANDINI R D

1^st year pg SCHOLAR

DEPT. OF PANCHAKARMA

AYURVEDA MAHAVIDYALAYA, HUBLI-580024

GUIDE

Dr. PADMAVATI VENKATESH

M. D (Ayu), PROFESSOR

PG DEPT. OF PANCHAKARMA

AYURVEDA MAHAVIDYALAYA, HUBLI – 580024

CO-GUIDE

DR. RAMACHANDRA LATTI

                                                                        M.B.B.S M.D.

RTD PROFESSOR

DEPT. OF PHYSIOLOGY

PIMS RURAL MEDICAL COLLEGE

LONI, MAHARASTRA STATE

2022-2023

AYURVEDA MAHAVIDHYALAYA

HUBLI – 580024

From,

           DR. NANDINI R D

PRELIMINARY M.D (Ayu) SCHOLAR

DEPARTMENT OF PANCHAKARMA

AYURVEDA MAHAVIDYALAYA, HUBLI.

To,

           THE REGISTRAR

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

Through,

            THE PRINCIPAL AND

    HEAD OF THE DEPT,

    DEPARTMENT OF PANCHAKARMA

    AYURVEDA MAHAVIDYALAYA, HUBLI – 580024

Respected Sir,

Sub: Submission of completed proforma for registration of subject for dissertation

I would request you to kindly register the below mentioned subject which has been reviewed and clarified, against my name for the submission of the dissertation to the Rajiv Gandhi University of Health Sciences, Bangalore, for the partial fulfilment of M.D (Ayu) in Panchakarma.

Title of Dissertation:

A RANDOMISED CONTROLLED TRAIL TO EVALUATE THE EFFICACY OF AYURVEDA INTERVENTION (NITYA VIRECHANA) AS AN ADD-ON TO STANDARD CARE IN SECONDARY HYPERLIPIDEMIA. Here with, I am enclosing the completed proforma for the registration of subject of dissertation.

Thanking You

Place: Hubli                              Yours Faithfully

Date: 28/10/2023                                        (Dr. NANDINI R D)

RajIv Gandhi University Of Health SciEnces

BANGALORE, KARNATAKA

ANNEXURE – II

PROFORMA for registration of subject for dissertation

6.   BRIEF RESUME OF INTENDED WORK:

6.1 NEED FOR THE STUDY:

Sedentary life style, stress, untimely and disturbed sleep patterns, various addictions, unhealthy dietetic deviations contribute vital role in the manifestation of lifestyle disorders. The enlisted factors impair metabolic activities at GIT level as well as cellular level making one prone to series of disorders. Hyperlipidaemia is one such disorder identified as a potential risk factor for multitudes of diseases like metabolic syndrome, hypertension, stroke, cardiovascular diseases. Hyperlipidaemia is one of the burning issue in today’s era. Hyperlipidaemia is classified as familial also known as primary hyperlipidaemia caused by specific genetic abnormalities and acquired also known as secondary hyperlipidaemia resulting from another underlying disorder that leads to alterations in plasma lipid and lipoprotein metabolism.¹ 

Secondary Hyperlipidaemia is lipoprotein metabolic disorder with abnormal elevated levels of cholesterol, cholesterol esters, and triglycerides in plasma.²Lipid and lipoprotein deviations are extremely common in general population and are regarded as modifiable risk factors for Cardiovascular Disease due to their influence on Atherosclerosis.³

NCEP (National Cholesterol Education Programme) ATP III guidelines III of united states recommended cholesterol levels less than 200mg/dl whereas values exceeding 240mg/dl are considered as high-risk factor. Raised cholesterol (>220mg/dl) is prevalent in 60% population of India, whereas in males it is prevalent in 45% individuals and 15% in females. HDL reported values 28.2% in males and 12.9% females have HDL below1mmol/L.⁴

Secondary Hyperlipidaemia is relatively asymptomatic condition as far as patient undergoes investigations or reported ischemic changes hence termed as silent killer. Secondary Hyperlipidaemia is the foundation of multiple metabolic disorders including various fatal conditions like IHD, Stroke, and CCF (Congestive Cardiac Failure) etc. To combat this and to break the chain sincere efforts and extensive experimental studies are going on. In 2018 lipid-lowering guidelines came out with suggestion of administration of new lipid-lowering drugs. But most of these modern drugs are potentially toxic, costly and are contraindicated in hepatic or renal impairment, gall bladder diseases and during pregnancy⁵. Diagnosed Secondary Hyperlipidaemia individuals try their level best by adopting various types of fasting, fat free diet, supplement of lipids and exercises before approaching hospitals. In-spite of multiple sincere efforts fail to lower raised cholesterol levels significantly makes patients to get frustrated. Here, Ayurveda can intervene by modification of risk factors and prevention of undue complications.

Direct clinical reference is not available in Ayurveda classics correlating to Hyperlipidaemia. There are scattered references available in Ayurveda which can nearly be co-related to Raised ‘Medas’ in Rasayani upto certain extent. As per Ayurveda, Medo Dhatu, Vasa and Majja Dhatu possess similarity of Snehatwa and so lipids metabolism can be correlated with the above said Dhatu vyapar. Attempts are being made to co-relate this condition clinically to ‘Raktagatsneha Vriddhi’, ‘Rasaraktagat-sneha Vriddhi’, Medovriddhi, ‘Medoroga’, ‘Sthaulya’ etc by various scholars of Ayurveda.

 Hyperlipidaemia is Santarpanajanya bahudosha Medo Dhatupradoshaja condition. Repeated ingestion of excessive Kapha and Meda vruddhikar factors hamper Prathama  Avasthapaka to make partial digestion of Annarasa. Quantitative increase and functional impairment of Kapha Dosha results in lack of perfect end product of fat metabolism that tends to remain in blood vessels. This Amatwa at Medovaha Srotas plays significant role in initial pathophysiology. The qualities are comparable- the raised lipids can be linked to Sneha,  Baddha  and/ or Abaddha  Medas along with  Sama  Rasa embedded in Rasayani.

          Hyperlipidaemia is Bahudosha avasta caused due to altered functioning of thermochemical energy considered as Agni. This study is intended to treat Hyperlipidaemia through new interventional concept of Nitya Virechana to eliminate Bahudosha in small quantity on daily basis. Drugs selected for Nitya Virechana mainly possess Tikta-Katu Rasa with Laghu, Rooksha and Tikshana Guna that aids in Sneha-Meda-Kleda Shoshana along with Lekhana.

6.2 REVIEW OF LITERATURE:

The Review of Literature includes screening of classical Ayurveda Literature, Modern Literature’s, scientific Journals and verified, authentic Internet sources to collect sufficient data for the study.

1. Description of Santarpana janya Vyadhi^6,7

2. Description of Bahudosha Avastha Lakshana.⁸

3. Description of Hyperlipidaemia⁹

4. Description of Nitya Virechana¹⁰

5. Description of Nitya Virechana in Bahudosha Avastha¹¹

 PREVIOUS WORK DONE:

1. Dr. Sreelakshmi C: Role of Ooshakadi Lekhana Basti in the management of Medopradoshajavikara w.s.r.t Hyperlipidaemia. GAMC Bangalore: RGUHS 2005.

2. Dr. Shilpa A: A comparative study on the efficacy of Virechana Karma and Badaradi Asthapana Basti in Medoroga w.s.r.t Hyperlipidaemia. GAMC Bangalore: RGUHS 2010.

3. Dr. Sumedha K A:  A comparative clinical study on Snehapana by two methods with Murchita Tila Taila followed by Virechana in Hyperlipidaemia. GAMC Bangalore : RGUHS 2013.

4. Dr. Aparna.K: A comparative clinical study to assess Virechana karma with Vidanga Tanduladi Yoga and Harithakyadi Modaka in Hyperlipidaemia. GAMC Bangalore : RGUHS 2017

5. Dr. Reeny Ravindra D: A randomized open labelled comparative clinical study to evaluate the efficacy of Virechana with and without Snehapurva Rukshana in the management of Dyslipidaemia. Sri Jagadguru Gavisiddeshwar Ayurvedic medical college, Koppal: RGUHS 2018

6. Dr. Ganesh Pai K: A comparative clinical study to evaluate the efficacy of Shodhananga Snehapana and Basti as Pravicharana with Murchita Tila taila in the management of Hyperlipidaemia. GAMC Mysore: RGUHS 2019.

7. Dr. Aishwarya Raman Gowda: A clinical study to evaluate the effect of Bahya and Abhyantara Rukshana in Shonita Abhishyanda w.s.r.t Hyperlipidaemia. Shri D G Melmalagi Ayurvedic Medical College and Hospital Gadag: RGUHS 2020.

8. Padmavati Venkatesh, Chinmayee Mohanty, & Rupendra Kumar Sahu. (2022). Role of Ubhaya Shodhana in Hyperlipidaemia- A Case Report. Journal of Ayurveda and Integrated Medical Sciences, 7(4),136 - 140. Retrieved from https://jaims.in/jaims/article/view/1814

6.3 AIM OF THE STUDY:

· To evaluate the effect of Nitya Virechana in the management of Secondary Hyperlipidaemia.

      OBJECTIVES OF THE STUDY:

· To evaluate the efficacy of Ayurveda intervention (Nitya Virechana) as adjunct to standard care in the management of Secondary Hyperlipidaemia.

· To study Secondary Hyperlipidaemia in detail as per Contemporary science and Ayurveda

6.4 HYPOTHESIS:

· H₀ -Combined effect of Standard care and Nitya Virechana as an add-on is not effective than Control group.

· H₁ -Combined effect of Standard care and Nitya Virechana as an add-on is clinically effective than Control group.

6.5 STUDY DESIGN:

7. MATERIALS AND METHODS:

The present study titled A RANDOMISED CONTROLLED TRAIL TO EVALUATE THE EFFICACY OF AYURVEDA INTERVENTION (NITYA VIRECHANA) AS AN ADD-ON TO STANDARD CARE IN SECONDARY HYPERLIPIDEMIA is a clinical trial which will be done with the following materials:

7.1 SOURCE OF DATA:

· Literary review will be done from the literature available from Central and Panchakarma Departmental library of Ayurveda Mahavidyalaya, Hubli, as well as from the modern text book, journals and Research publications. And also from internet-search engines like PubMed, Scopus, DHARA, Ayush Research Portal with keywords- Hyperlipidaemia, Santarpanajanya vyadhi, Medoroga, Nitya Virechana.

· Patient attending the Outpatient and Inpatient Department of Ayurveda Mahavidyalaya, Hubli will be identified as per inclusion-exclusion criteria and will be enrolled in the study.

· Proposed medicines to be used as Ayurveda interventions will be prepared in the Department of Rasa Shastra and Bhaishajya Kalpana, Ayurveda Mahavidyalaya, Hubli.

7.2 METHODS OF COLLECTION OF DATA:

· An informed written consent will be taken after communicating all the details of the     study in the language best understood to patient.

· The subjects will be selected randomly using simple random sampling method, irrespective of caste, religion, gender and locality.  

· A designed CRF (case record form) will be prepared with all the necessary points of demography, family history, personal history, diet and lifestyle details, Nidana-Panchaka (assessment of causative factors, pathogenesis, prodromal symptoms, signs-symptoms, exacerbating/ relieving factors) as quoted in Ayurveda literature.

· The selected subjects will be subjected to detailed clinical history and complete physical examination before enrolling into the clinical study.

7.3 SOURCE OF DRUG:

Following drugs and materials will be procured from GMP certified Ayurveda drug manufacturers.

· Trikatu Churna ¹² for Amapachana.

· Eranda Sneha Bharjita Triphala, Aragwadha and Katuki churna for Nitya virechana.

Quantity of Dravyas designed in the ratio 6:6:3 respectively and Erand sneha Q.S. for Nitya Virechana. The drug will be processed as per Charaka Kalpastahana.¹³

A: CRITERIA FOR DIAGNOSIS:

     According to new modified NCEP (National Cholesterol Education Program) Adult          Treatment Panel III guidelines, ¹⁴ following range of values will be considered for diagnosis of hyperlipidaemia.

B: INCLUSION CRITERIA:

1. Patients of all genders between the age group of 20-65 years who fulfil the criteria of Objective and Subjective parameters.

2. Controlled HTN - <140/90 mm of Hg.

3. Controlled NIDDM -HbA1C <7%.

4. Patients fulfilling the diagnostic criteria of Hyperlipidaemia.

5. Patients already on Antilipidemic drugs since 0-10years.

6. Patients fit for Nitya Virechana.

C: EXCLUSION CRITERIA:

1. Patients newly diagnosed and not on Antilipidemic drugs.

2. Induced Hyperlipidaemia due to prolonged intake of Glucocortiosteriods.

3. Patients suffering from major systemic illness necessitating long term drug treatment (Rheumatoid arthritis, Tuberculosis, Psycho-Neuro-Endocrinal disorders, CKD, Nephrotic Syndrome, Liver disorders etc.)

4. Patients with a past history of Atrial Fibrillation, Acute Coronary Syndrome,  

5. Patient with evidence of malignancy.

6. Pregnant and lactating women.

SAMPLE SIZE â€“ 60

GROUPING:  Sixty subjects who fulfil the inclusion criteria and are willing to participate for the study will be assigned in two groups in equal numbers i.e. 30 patients in each group randomly.

· Group -A: Nitya Virechana along with Standard care for Secondary hyperlipidaemia.

·  Group-B: Standard care for Secondary hyperlipidaemia alone.

D: INTERVENTIONS:

Group A: Nitya Virechana along with Standard care as per ACC/AHA Lipid guidelines for the management Secondary Hyperlipidaemia for period of 45 days.

 Group B : Standard care as per ACC/AHA Lipid guidelines for the management Secondary Hyperlipidaemia for period of 45 days.

· Nitya Virechana Regime:

a. Amapachana with Trikatu churna 5gms per day before food twice a day till Nirama Lakshana appearance.

b. Nitya Virechana given with Eranda Taila Bharjita Triphala, Katuki and Aragvadha based on Agni and Koshtha bala.

c. Administration Time: Prataha kala.

d. Anupana – Ushna Jala.

TOTAL DURATION:  45DAYS

FOLLOW UP AFTER 15 DAYS.

WITHDRAWAL CRITERIA:

          The participants will be allowed to withdraw from the trial if there is any major ailment necessitating the institution of new modalities of treatment. The decision to withdraw a participant from the trial will be taken by the principal investigator with proper justification and formal information to the ethical committee within two working days.

CRITERIA FOR ASSESSMENT OF EFFECT OF THERAPY

SUBJECTIVE PARAMETER:

OBJECTIVE PARAMETER:

1. Lipid profile

Risk levels according to the NCEP (National Cholesterol Education Program) ATP III guidelines¹⁵. For better assessment following ranges are graded as follows-  

2.   Body Mass Index.

3.  Waist Circumference.

4.   Body circumference measurements:

· Chest – In normal expansion, at the level of nipple.

· Waist – At the level of the umbilicus.

· Pelvis - At the level of the highest point of distension of the buttocks

· Mid arm – Middle of the arm between the shoulder joint and elbow joint

· Mid-thigh- Mid of the thigh between the hip joint and the knee joint

· Mid-calf – Middle of the calf between the knee joint and the ankle joint.

5.  Skin fold thickness:

    Skin fold thickness using vernier callipers before and after treatment in below regions

· Middle portion of the biceps muscle

· Middle portion of the triceps muscle

· Abdomen

· Thigh

Karma Assessment:

Nitya Virechana:

· Swaroopa of  Mala.(Colour and consistency)

· Vegas of Mala.

·  GI and Systemic Observations.

Overall effect of the intervention will be estimated in the following 5 categories:

· Complete remission          100%

· Marked improvement       75 - 99%

· Moderate improvement    50 - 74%

· Mild improvement            25 - 49 %

· Un-changed                      < 25 %

STATISTICAL TESTS TO BE USED:

The statistical tests chosen in this study considering Subjective and Objective parameters Paired t test will be used to find out t and p value. To compare the effect of therapy between the groups Mann Whitney Test will be used along with this appropriate test will be considered.

LABORATORY INVESTIGATIONS:  

The following investigations will be done before and after treatment to rule

out any other associated pathology as well as to assess the changes after the treatment and also as safety parameters.

· Blood : Hb %

· Biochemical: HBA1C, Lipid profile.

· Urine : Routine

· USG Abdomen and pelvis

The following test will be done (If required)

· ECG

· 2D Echo

· LFT

· RFT

· Sr. Creatinine 

· Thyroid profile

· Colour Doppler ( only if any coagulopathy suspected clinically or patient previous medical history relevant)

7.3 DOES THIS STUDY REQUIRE ANY INVESTIGATIONS OR INTERVENTION TO BE CONDUCTED ON PATIENTS OR ANIMALS?

                                                             YES.

       This study will be conducted clinically. No animal experiments will be carried out.

· HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION?    

YES.

Ethical clearance has been obtained by the ethical committee constituted by Ayurveda Mahavidyalaya, Hubli and written consent will be taken from each subject or by an attendant if the subject is illiterate, on a printed consent form.

8. REFERENCES:

1. https://en.wikipedia.org/wiki/Hyperlipidemia#cite_note-DorlandAndAmericanHeritage-2

2.  â€œHyperlipidaemia”. The Free Dictionary. Citing: Dorland’s Medical Dictionary for Health Consumers. Saunders. 2007 and The American Heritage Medical Dictionary. Houghton Mifflin Company. 2007. ISBN 978-0618824359.

3. Lilly L (2015). Pathophysiology of heart disease : a collaborative project of medical students and faculty. Wolters Kluwer. ISBN 978-1496308696. OCLC 1052840871.

4. Executive summary of the Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.

5. _https://vascular.org/patients-and-referring physicians/conditions/hyperlipidemia.

6.  Agnivesha, Charaka Samhita with Ayurveda Deepika commentary of Chakrapanidatta revised by Charaka and Dridhabala, edited by Vd.Harish Chandra Singh Kushawaha, published by Chaukamba pblishers, edition 2018,  Sutra Sthana  23^rd chapter page no.327-329.

7. Agnivesha, Charaka Samhita with Ayurveda Deepika commentary of Chakrapanidatta revised by Charaka and Dridhabala, edited by Vd.Harish Chandra Singh Kushawaha, published by Chaukamba publishers, edition 2018,  Nidana  Sthana  4^th chapter page no..

8. Agnivesha. Charaka samhita, revised by Charaka and dridhabala, with Ayurvedadeepika Commentry of Chakrapanidatta edited by Vaidya Yadavji Trikamji Acharya Varanasi: Chowkambha Orientalia: reprint 2014. Sutra Sthana 16^th chapter, Shloka 13-16, page 97.

9. Harrison’s Principles of Internal Medicine, 20edition.

J. Larry Jameson, Anthony S. Fauci, Dennis L. Kasper, Stephen L. Hauser, Dan L. Longo, Joseph Loscalzo

10. Dr. Kevala Krishna Thakaral. Sushruta Samhita, Chowkambha Orientalia: reprint 2017. Sushruta Samhita Chikithsa Sthana 9^th chapter, shloka 68, page-309.

11. Agnivesha. Charaka Samhita, revised by Charaka and Dridhabala, with Ayurvedadeepika Commentry of Chakrapanidatta edited by Vaidya Yaadavji Trikamji Acharya Varanasi: Chowkambha Orientalia: reprint 2009. Charaka Samhita Chikithsa Sthana 13^th chapter, Shloka 61, page-495.

12. Agnivesha, Charaka Samhita with Ayurveda Deepika commentary of Chakrapanidatta revised by Charaka and Dridhabala, edited by Vaidhya Yadavji Trivikramji Acharya, published by Chaukamba publishers, edition 2020, Sutrasthana 15/9-12, pg no 94.

13. Agnivesha. Charaka Samhita, revised by Charaka and Dridhabala, with Ayurvedadeepika Commentry of Chakrapanidatta edited by Vaidya Yadavji Trikamji Acharya Varanasi: Chowkambha Orientalia: reprint 2014. Kalpa Sthana 12^th chapter, Shloka-48-49, page-682.

14. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001 May 16;285(19):2486-97. [PubMed]

15. National Cholesterol Education Program National Heart, Lung, and Blood Institute National Institutes of Health NIH Publication No. 01-3670 (May 2001).