| CTRI Number |
CTRI/2020/05/025332 [Registered on: 23/05/2020] Trial Registered Prospectively |
| Last Modified On: |
31/03/2021 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Ayurveda |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
Ashwagandha for prevention against SARS-CoV-2 Infection: A Randomized Hydroxychloroquine Controlled drug trial in high risk Health Care Providers |
Scientific Title of Study
Modification(s)
|
Ashwagandha for the Prophylaxis against SARS-CoV-2 Infection: A Randomized Hydroxychloroquine Controlled Clinical Trial in Health Care Providers |
|
Secondary IDs if Any
|
| Secondary ID |
Registry |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
DR ARVIND CHOPRA |
| Address |
11 HERMES ELEGANCE
1988 CONVENT STREET
CAMP PUNE
11 HERMES ELEGANCE
1988 CONVENT STREET
CAMP PUNE 411001
MAHARASHTRA
Pune
MAHARASHTRA
411001
India |
| Phone |
91-20-26344099 |
| Fax |
91-20-26350084 |
| Email |
crdp5624@gmail.com |
|
Details Contact Person
Scientific Query
|
| Name |
DR ARVIND CHOPRA |
| Address |
11 HERMES ELEGANCE
1988 CONVENT STREET
CAMP PUNE
11 HERMES ELEGANCE
1988 CONVENT STREET
CAMP PUNE 411001
MAHARASHTRA
Pune
MAHARASHTRA
411001
India |
| Phone |
91-20-26344099 |
| Fax |
91-20-26350084 |
| Email |
crdp5624@gmail.com |
|
Details Contact Person
Public Query
|
| Name |
DR ARVIND CHOPRA |
| Address |
11 HERMES ELEGANCE
1988 CONVENT STREET
CAMP PUNE
11 HERMES ELEGANCE
1988 CONVENT STREET
CAMP PUNE 411001
MAHARASHTRA
Pune
MAHARASHTRA
411001
India |
| Phone |
91-20-26344099 |
| Fax |
91-20-26350084 |
| Email |
crdp5624@gmail.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
MINISTRY OF AYUSH |
| Address |
AYUSH BHAWAN, GPO COMPLEX, NEW DELHI 110023 |
| Type of Sponsor |
Government funding agency |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH |
ANUSANDHAN BHAWAN, 2 RAFI MARG, NEW DELHI 110001 |
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 12 |
| Contact Person |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Anand More |
All India Institute Of Ayurved |
Sarita Vihar ,
Gautam Puri , Mathura Road , New Delhi 11076
New Delhi
|
09422025732
drmoreanand@gmail.com |
| Dr Jaya Chakravarty |
Banaras Hindu University |
Dept of General Medicine, IMS, Varanasi 221005
Varanasi
|
9453003725
tapadar@gmail.com |
| DR ABHAY UPPE |
D Y Patil University School of Medicine and Hospital |
Nerul, Navi Mumbai 400 706
Mumbai
|
9769319554
abhay.uppe@dypatil.edu |
| Dr Dilip Gode |
Datta Meghe Institute of Medical Sciences |
Nagpur 440022
Nagpur
|
9822737919
dilipgode@yahoo.com |
| Dr Padmakar Somavanshi |
Dr Panjabrao Alias Bhausaheb Deshmukh Memorial Medical College |
Panchvati Square, Morshi Rd, Amravati, Maharashtra 444603
Amravati
|
09822229855
drpdmmc2007@rediffmail.com |
| Dr Deepti Talmohite |
ESI Hospital |
Akurli Road, Kandivali (East)
Mumbai
|
9869268694
dr.deeptir.talmohite@esic.nic.in |
| Dr Akaksh Khobragade |
Grant Govt. Medical College & Sir J.J. Group of Hospital |
Byculla, Mumbai 400008
Mumbai
|
9702658822
akash.khobragade@gmail.com |
| Dr Sandhya Kamat |
GS Medical College & KEM Hospital |
Acharya Donde Marg, Parel, Mumbai: 400012
Mumbai
|
9820165681
drsandhyakamat@gmail.com |
| Dr Himanshu Reddy |
King George Medical University |
Shah Mina Rd, Chowk, Lucknow, Uttar Pradesh 226003
Lucknow
|
09839266822
dr.himanshu.reddy@gmail.com |
| Vaidya Manohar Gundeti |
RRAP Central Ayurveda Research Institute for Cancer CCRAS |
Podar Medical Campus, Dr A B Road, Worli, Mumbai, 400018.
Mumbai
|
9004960133
drmanoharccras@gmail.com |
| Dr Manish Patel |
Sardar Vallabhbhai Patel Institute of Medical Sciences and Research |
Ellisbridge, Ahmedabad
Ahmadabad
|
9909973747
patel005manish@yahoo.co.in |
| Dr Renuka Munshi |
TN Medical College & BYL Nair Hospital |
Dr. A. L. Nair Road, Station, near Mumbai Central
Mumbai
|
9823377409
renuka.munshi@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 12 |
| Name of Committee |
Approval Status |
| All India Institute of Ayurveda, |
Approved |
| DATTA MEGHE INSTITUTE OF MEDICAL SCIENCES, INSTITUTIONAL ETHICS COMMITTEE |
Approved |
| Ethical Committee, Dr PDM Medical College |
Approved |
| Ethics Committee for Academic Research Projects TN Medical College and BYL Nair Hospital |
Approved |
| INSTITUTE OF MEDICAL SCIENCES, BANARAS HINDU UNIVERSITY, INSTITUTIONAL ETHICS COMMITTEE |
Approved |
| Institutional Ethics Committe, Grant Government Medical Collegee, Sir J J Group of Hospitals |
Approved |
| INSTITUTIONAL ETHICS COMMITTEE SETH GS MEDICAL COLLEGE AND KEM HOSPITAL |
Approved |
| INSTITUTIONAL ETHICS COMMITTEE, D Y PATIL UNIVERSITY SCHOOL OF MEDICINE |
Approved |
| Institutional Ethics Committee, Employees State Insurance- Postgraduate Institute of Medical Sciences and Research Model Hospital |
Approved |
| Institutional Ethics Committee, NHL Municipal Medical College e, |
Approved |
| KGMU Institutional Ethics Committee |
Approved |
| R R A Podar Central Ayurveda Research Institute for Cancer |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Healthy Human Volunteers |
B972 |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Intervention |
Ashwagandha (Withania somnifera |
Ashwagandha has immunomodulant and immune enhancing activity. It is anti oxidant and promotes health
250 mg, 2 tablets twice a day for 12 weeks |
| Comparator Agent |
Hydroxychloroquine |
HCQ is considered to be anti viral and anti inflammatory.
400 mg tablet.
400 mg tablet twice a day on Day 1, 400 mg once a week for 7 weeks |
|
Inclusion Criteria
Modification(s)
|
| Age From |
20.00 Year(s) |
| Age To |
69.00 Year(s) |
| Gender |
Both |
| Details |
1.Participants of either sex, 20 to 69 years of age
2.Participants tested negative for COVID-19 by nose and throat swab using RT PCR technique
3.HCQ naïve participants
4.Willing to come for regular follow – up visits
5.Written Informed Consent
|
|
| ExclusionCriteria |
| Details |
1.Participants with hypersensitivity or Intolerance and contraindications (psoriasis, porphyria and Glucose-6-Phosphate Dehydrogenase deficiency)
2.Pregnant women, lactating women and women of child bearing potential not willing to follow adequate contraception
3.Participants with known allergy or contraindication to Ashwagandha
4 Have any Chronic,Severe,Unstable,Uncontrolled medical disease such as Diabetes Hypertension, Cardiac disorders, liver, kidney disorders and lung disorders or other disease of concern which may put the participant at increased risk during the study
5.History of having received any investigational drug in the preceding one month.
6.Prolonged concurrent intake of any drug that is known to prolong QT interval on the ECG as per physician discretion and these drugs include anti-arrhythmic drugs, quinidine, chlorpromazine, haloperidol, olanzapine, thioridazine, fluoxetine, antibiotics belonging to quinolone and macrolide family, antibiotics, fenfluramine and other appetite suppressants, Beta-2 agonists, terfenadine and other anti- histaminic drugs, liquorice and potassium loweringdrugs
7.History of taking any kind of Ayurvedic formulation or any other form of CAM (Complementary Alternative Medicine) therapy in the preceding 2 months
8.Unwilling to come for regular follow-up for the entire duration of the study.
9.Non – co-operative attitude of the participant
10.Any condition that, in the opinion of the investigator, does not justify the participant’s inclusion in the study.
Liver enzymes > 1.5 times of upper normal limits, Serum creatinine > 2 mg/dL, Blood urea > 70 mg/dL
|
|
|
Method of Generating Random Sequence
|
Permuted block randomization, fixed |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
(i)Proportion of SARS-CoV-2 infection free participants on completion of study
(ii)Proportion of participants contracting COVID-19 during the study period
|
WEEK 12 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| proportion of participants developing COVID-19, drug related adverse event, drug tolerability, General Health Related Questionnaire (behavior, habit and fitness/ HR-BHF), Quality of life (WHO QOL Brief), Ayurveda measures, Immune Status (serology for specific anti SARS-CoV-2 IgM and IgG antibodies) |
week 12 |
|
|
Target Sample Size
|
Total Sample Size="400"
Sample Size from India="400" |
|
Phase of Trial
|
Phase 2 |
Date of First Enrollment (India)
Modification(s)
|
28/05/2020 |
| Date of First Enrollment (Global) |
No Date Specified |
|
Estimated Duration of Trial
|
Years="0"
Months="3"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
Publication Details
Modification(s)
|
Not Yet Applicable |
Brief Summary
Modification(s)
|
There is an urgent need for effective and safe chemoprophylaxis against Severe Acute Respiratory Syndrome - Corona Virus-2 (SARS-CoV-2). There is no drug or any vaccine available. Several effective non-drug methods of protection are being vigorously followed but still the morbidity and mortality in COVID-19 is striking. ICMR has issued an advisory on empirical use of Hydroxychloroquine (HCQ) in high risk individuals and thousands of Health care providers (HCP) are following a weekly regiment for seven weeks with utmost caution against drug related toxicity. However, the clinical evidence so far for the anti-viral efficacy of HCQ is sparse and its use is mostly based on in-vitro ex-vivo studies. ICMR has stated that ‘proof of concept and pharmacokinetic studies’ (HCQ) will be required expeditiously. The pandemic is likely to last longer requiring a drug with more prolonged efficacy and better safety. A drug that enhances immunity and has some anti-viral effects may be a good option. Ashwagandha, ancient well known Ayurveda ‘Rasayana’, is popularly used to build immunity in several medical disorders and has demonstrated unequivocal beneficial effect on the immune cells and system in laboratory experiments for over 3 decades. Clinically, it is shown to be a good immunomodulatory drug in intensely inflammatory autoimmune disorders like rheumatoid arthritis. It is also a potent anabolic and anti-oxidant agent. Of late, it was shown to interfere with the binding of SARS-CoV-2 to the host cell receptor (ACE 2) but this is not yet validated.
Ministry of AYUSH and CSIR GOI has initiated a comprehensive clinical drug trial to study the clinical efficacy and safety of Ashwagandha in the prophylaxis against COVID-19 in HCP. Consenting and eligible HCP will be randomized to either of the two intervention arms- HCQ (standard use as per ICMR advisory) and Ashwagandha (experimental as per Ayurveda expertise) with a caveat that the individual will be permitted to refuse the randomized allocation at baseline and exercise personal choice to switch over to the alternate allocation (Zelen Model of randomization). Further, the design will be that of an open label phase, parallel efficacy multicentre drug trial. The sample size is calculated for an equivalence design (7.5% two sided) with a statistical power of 80% and an alpha significance at two sided p<0.05. With adjustments for withdrawals and a reduction in power due to Zelen model, it is estimated to enrol 200 participants in either arm of the study. While the weekly use of HCQ will stop after 7 weeks (ICMR advisory), the daily use of Ashwangandha will continue till study completion. The duration of the study for all participants will be 12 weeks with a daily monitoring of COVID-19 symptoms using a mobile app. Physician centric evaluations will be done by both Ayurvedic and Allopathic physicians at baseline and every 4-week thereafter till study completion. Quality of life and general health will be assessed using suitable questionnaires. Nasal and throat swabs will be collected and tested repeatedly for SARS-CoV-2 RNA using real time RT-PCR along with special assays for selected cytokines and neutralizing antibodies (IgM and IgG). Routine blood tests will be carried out for an overall assessment of health. The primary efficacy measure is the proportion of study participants free of SARS-CoV-2 and COVID-19 on study completion. There are several secondary efficacy measures including pertaining to Ayurveda assessment and safety and tolerability (drug).The drug trial will strictly adhere to the standard guidelines on drug trials (especially human subjects, GCP, adverse event reporting) from Declaration of Helsinki, WHO and ICH (2017), ICMR (2018) and AYUSH/CCRAS (2018).
|
