Ayurveda for promoting recovery in long COVID
| ISRCTN | ISRCTN12368131 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12368131 |
| EudraCT/CTIS number | 2020-005789-33 |
| IRAS number | 293329 |
| Secondary identifying numbers | IRAS 293329 |
- Submission date
- 03/08/2022
- Registration date
- 15/08/2022
- Last edited
- 11/03/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
This study is a double-blind randomised placebo-controlled trial aiming to evaluate the effectiveness of an Indian traditional herb, Ashwagandha, for promoting recovery in people experiencing ongoing symptoms of Long COVID.
‘Ashwagandha’ (Withania somnifera) has been used for centuries as part of the traditional Indian Ayurvedic system of medicine for promoting energy and vitality, reducing stress and boosting the immune system. Recently, a number of small and medium randomised trials in humans have demonstrated its potential effectiveness for reducing many of the symptoms characteristic of long COVID. Ashwagandha has a well accepted safety profile as is available over the counter as a herbal supplement in the UK.
Who can participate?
Adults over 18 years, diagnosed with long COVID.
What does the study involve?
Participants will be recruited through select recruiting GP practices based across the UK. They will take trial medication for 3 months which will be sent to their house via post.
Follow-up surveys to assess their functional status, quality of life, symptom burden and work status will be conducted by online or postal questionnaires. Clinical monitoring to assess safety will be conducted monthly and at the end of the trial, remotely or in-person, through participating GP practices.
What are the possible benefits and risks of participating?
The study may not benefit participants directly, but the information we get from the study will help our knowledge and understanding of how to treat long-term symptoms of COVID-19, for which there is currently no proven medical treatment or cure. Ashwagandha is considered a safe herbal medication which is widely used in India and globally. However as with all medications, there is a possibility that allergic reactions or side effects may occur. If participants experience any side effects or unusual symptoms they should let their study doctor know as soon as possible.
Where is the study run from?
London School of Hygiene & Tropical Medicine (UK)
When is the study starting and how long is it expected to run for?
July 2021 to November 2024
Who is funding the study?
Ministry of AYUSH, Government of India (through the All India Institute of Ayurveda (AIIA), an autonomous institution under the Ministry of AYUSH)
Who is the main contact?
Prof. Sanjay Kinra, sanjay.kinra@lshtm.ac.uk
Dr Poppy Mallinson, poppy.mallinson1@lshtm.ac.uk
apriltrial@lshtm.ac.uk
Contact information
Principal Investigator
LSHTM
Keppel Street
London
London
WC1e 7HT
United Kingdom
 ORCID ID |
0000-0001-6690-4625 |
|---|---|
| Phone | +44(0)20 7927 2088 |
| sanjay.kinra@lshtm.ac.uk |
Scientific
LSHTM
Keppel Street
London
WC1E 7HT
United Kingdom
| ORCID ID |
0000-0002-7591-8065 |
|---|---|
| Phone | +44 7510 382 984 |
| poppy.mallinson1@lshtm.ac.uk |
Public
LSHTM
Keppel Street
London
WC1E 7HT
United Kingdom
| Phone | +44 7510 382 984 |
|---|---|
| manisha.joshi@lshtm.ac.uk |
Study information
| Study design | Multicenter randomized double-blind placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | GP practice |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | Clinical trial of Ashwagandha for promoting recovery from COVID-19 in the UK |
| Study acronym | APRIL |
| Study hypothesis | Ashwagandha can improve functional status, quality of life and alleviate symptoms in UK adults suffering from long-term symptoms of Covid-19. |
| Ethics approval(s) |
Approved 25/07/2022, Wales Research Ethics Committee 3 (Health and Care Research Wales, Castle bridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, United Kingdom; +44 2920 230457; Wales.REC3@wales.nhs.uk), ref: 22/WA/0157 |
| Condition | Long COVID |
| Intervention | Trial design: Randomised double-blind placebo-controlled trial. Interested adults who are diagnosed with long COVID (defined as per NICE guidelines - NG188) that affect and limit their everyday activities will be randomised to take Ashwagandha or placebo for 3 months (delivered at home by post). Participants will be recruited through participating GP practices based across the UK. Eligible participants will be approached by the participating GP's team and trial discussed in detail. Participant Information Sheet (PIS) will be emailed/posted to them or handed to them (if seen face-to-face) at least 1-2 days before signing the informed consent form (ICF). Participants will be able to go through the PIS and ask questions and discuss the trial information with research staff, their family and friends before taking a decision. Participants will be able to sign the ICF online or a paper copy will be posted to them. All ICFs will be verified and stored safely in the Investigator Site File (ISF) by the recruiting GP sites. After signing ICF, participants will have a consultation with the recruiting doctor (study investigator) for clinical assessment and eligibility. This may be in-person or by phone/video call. Participants will have a blood test to assess their liver function at screening. All WOCBP will have urine pregnancy done before taking trial medication to rule out pregnancy. All participants will follow contraception methods as described in the protocol. Once the participant is confirmed eligible, the trial team will formally enrol them into the study and baseline questionnaires will be sent out. On receiving completed baseline questionnaires, participants will be randomised in the trial. Randomisation: Blinded computer-based randomisation in 1:1 ratio after baseline questionnaires are received. Block randomisation will be used to ensure balance across the study recruitment period. Interventions: The intervention arm will receive Ashwagandha (aqueous root extract) at a daily dose of 1000mg in tablet form, taken twice daily (morning and evening) for 3 months (2x(2x250mg) tablets). The control arm will receive placebo tablet indistinguishable from Ashwagandha in appearance, to be taken as per the same regimen. Trial medication will be sent monthly by post with tracked delivery. The courier will confirm that the products were delivered to a member of the correct household and take the name and signature of the recipient. Receipt of the products by trial participant will be confirmed via text and/or phone call from the study team within 2 days. Follow-up: Participants will be followed-up monthly for 3 months. Each month clinical monitoring and safety assessment will be done by the recruiting doctor's team. All participants will have a blood test to assess their liver function after one month of trial medication and at the end of 3 months (end of the trial). All adverse events (AEs), serious adverse events (SAEs) will be promptly reported to the trials unit as described in the protocol. Patients will be further investigated and treated if required and if required medication will be discontinued or stopped as per clinical assessment and participant safety. All WOCBP will repeat a urine pregnancy test at the end of each month for 3 months to rule out pregnancy. If pregnant while on trial treatment they will discontinue trial treatment and report to their doctor immediately. For outcome assessment, participants will be asked to complete monthly online questionnaires for physical functioning, quality of life and symptoms. These will be sent to participants at the end of the first month, end of the second month, end of the third month. Automated email or text reminders will be sent as per participant preference. In case participants are unable or unwilling to complete surveys online, paper questionnaires in pre-paid return envelopes will be posted each month along with the trial medication packages. If participants fail to respond two months in a row, a follow-up call will be made to them. If they fail to respond then a phone call will be made to their nominated next of kin only to ascertain participant's wellbeing. Analysis: At the end of the trial, the results will be analysed according to a pre-specified analysis plan, comparing whether people in the Ashwagandha or Placebo group had better functional status after 3 months. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Ashwagandha (Withania Somnifera root extract) |
| Primary outcome measure | Self-reported functional status measured using the Post-COVID-19 Functional Status Scale (PCFS), at 3 months |
| Secondary outcome measures | Measured at baseline, 1 month, 2 months and 3 months 1. Quality of life by PROMIS 29+2 summary score 2. Self-reported fatigue, pain, sleep, anxiety, depression and social, physical and cognitive function by PROMIS 29+2 individual dimensions 3. Self-reported breathlessness by modified MRC Dyspnoea Scale 4. Health utility by EQ 5D-5L utility score 5. Self-reported work status and productivity 6. Other self-reported symptoms 7. Number of adverse events (3 months) |
| Overall study start date | 26/07/2021 |
| Overall study end date | 30/11/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 2500 |
| Participant inclusion criteria | 1. Adults (18 years or older) with the capacity to provide informed consent, and 2. Have been diagnosed with Long COVID as per the NICE Guidelines (NG188) – that is, either one of “Ongoing symptomatic COVID-19; signs and symptoms of COVID‑19 from 4 weeks up to 12 weeks”, or “Post-COVID-19 syndrome; Signs and symptoms that develop during or after an infection consistent with COVID‑19, continue for more than 12 weeks and are not explained by an alternative diagnosis. It usually presents with clusters of symptoms, often overlapping, which can fluctuate and change over time and can affect any system in the body. Post‑COVID‑19 syndrome may be considered before 12 weeks while the possibility of an alternative underlying disease is also being assessed”. The diagnosis will be confirmed by the participant’s GP and/or 3. medical records. 4. Report that their Long COVID has reduced their ability to carry out day-to-day activities compared with the time before they had COVID-19. 5. Willing and able to complete the study protocols (take trial medication regularly for 3 months, complete online telephone or postal surveys monthly, and participate in clinical monitoring assessment monthly) 6. Not taking any other herbal medicines, or willing to stop taking any such medicines for the duration of the trial. Herbal medicine is defined as a plant or plant part, or mixture or extract of these, which is taken in medicinal form to improve health, prevent disease, or treat illness |
| Participant exclusion criteria | 1. Self-diagnosed Long COVID in the absence of a clinical diagnosis as per the NICE Guidelines 2. Any medical condition or suspected medical condition which, in the opinion of the Investigator may present an unreasonable risk to the study participant as a result of his/her participation in this clinical study (this may involve conduct of any clinical assessment deemed necessary by the study investigator to confirm that this criterion is met, such as (but not limited to) validated psychiatric scales, ECGs, and laboratory tests for clinical chemistry, haematology, urinalysis, kidney function, etc). 3. Previous clinical diagnosis of severe psychiatric disorders 4. Abnormal liver function test results, as indicated by alanine aminotransferase or aspartate aminotransferase or total bilirubin >2 x ULN, either measured as part of routine care within past 3 months or conducted for the purposes of the clinical trial (if a recent test result is not available). 5. Previous clinical diagnosis of chronic kidney disease or other medical condition associated with impaired kidney function 6. Previous clinical diagnosis of heart disease or other cardiac problems 7. Use of any investigational products within 5 elimination half-lives after the last dose or at screening 8. History of malignancy unless resolved by adequate treatment with no evidence of recurrence 9. Hypersensitivity to the active substance or to any of the excipients 10. Women breastfeeding or with a positive urine pregnancy test at screening 11. Women planning to become pregnant for the duration of the participation in the study 12. Men and women of childbearing potential unwilling to adhere to the relevant contraception requirements for the duration of the study (until at least 24 hours after the final dose of trial medication is taken). Women of childbearing potential (WOCBP) are defined as all women who are: “fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, confirmation with more than one FSH measurement is required.” Acceptable contraception methods for WOCBP in this trial include: combined hormonal contraception, progestogen-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, sexual abstinence, or condom use. Sexual abstinence is defined as: “refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject”. Male participants are required to use condoms. All participants are required to inform investigator immediately if these contraception requirements are not met or if pregnancy is suspected. 13. Participants taking benzodiazepines, anticonvulsants, barbiturates or any other CNS depressants |
| Recruitment start date | 14/11/2022 |
| Recruitment end date | 31/08/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Leicester
LE3 1HN
United Kingdom
5 James Street
Morecambe
LA4 5TE
United Kingdom
Lymington Road
Highcliffe
Christchurch
BH23 5ET
United Kingdom
Cowplain
Waterlooville
PO8 8DL
United Kingdom
Bletchley
Milton Keynes
MK3 7QU
United Kingdom
Finchampstead
Wokingham
RG40 3RG
United Kingdom
Headington
Oxford
OX3 9JA
United Kingdom
Oxford
OX4 1JS
United Kingdom
15 Market Street
Oxford
OX1 3EF
United Kingdom
Reading
RG1 5BS
United Kingdom
London
W2 3ET
United Kingdom
37 Imrie PLACE
Penicuik
EH26 8LF
United Kingdom
Whinney Heys Road
Blackpool
FY3 8NR
United Kingdom
102 St Leonards Street
Edinburgh
EH8 9RD
United Kingdom
Sponsor information
University/education
Keppel Street
London
WC1E 7HT
England
United Kingdom
| Phone | +44 207 927 2626 |
|---|---|
| RGIO@lshtm.ac.uk | |
| Website | lshtm.ac.uk |
"ROR" |
https://ror.org/00a0jsq62 |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 01/02/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in publicly available repository |
| Publication and dissemination plan | Primary study results will be dissemination via a peer-reviewed publication in an open-access high-impact journal, as soon as possible after trial databases are locked. Following this, press releases and other public statements may be made. Additional publications arising from the trial (secondary analyses etc) will also be published in peer-reviewed journals. |
| IPD sharing plan | We will be asking consent from participants to put their de-identified data onto a public data repository. For patients who consent to this, we will review the data after databases are locked to ensure that confidentiality would be maintained, and put an appropriate data extract onto a public repository within 1 year of database lockdown. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 3 | 05/07/2022 | 15/11/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol file | version 4 | 01/03/2023 | 20/02/2024 | No | No |
Additional files
Editorial Notes
11/03/2025: Internal review.
29/08/2024: Penicuik Medical Practice, Blackpool Teaching Hospitals NHS Foundation Trust and Boroughloch Medical Practice were added to the study participating centres.
20/05/2024: The following changes were made to the trial record:
1. The overall end date was changed from 31/10/2024 to 30/11/2024.
2. The intention to publish date was changed from 30/11/2023 to 01/02/2025.
3. The plain English summary was updated to reflect these changes.
4. The study participating centre Lancaster Medical Practice was added.
15/03/2024: The recruitment end date was changed from 31/03/2024 to 31/08/2024.
20/02/2024: The following changes were made to the trial record:
1. Uploaded protocol v4 (not peer-reviewed) as an additional file.
2. The overall end date was changed from 30/09/2024 to 31/10/2024.
3. The study participating centres Whaddon Healthcare, Finchampstead Surgery, Hedena Health, St. Clements Surgery, Kes@northgate, Melrose Surgery were added.
4. The plain English summary was updated to reflect these changes.
17/08/2023: The following changes have been made:
1. The overall study end date has been changed from 31/12/2023 to 30/09/2024 and the plain English summary was updated accordingly.
2. The recruitment end date has been changed from 31/08/2023 to 31/03/2024.
3. Highcliff Medical Centre and Oaks Healthcare were added as study participating centres.
15/11/2022: The following changes were made to the trial record:
1. Protocol uploaded (not peer reviewed).
2. The recruitment start date was changed from 01/11/2022 to 14/11/2022.
3. Bay Medical Group was added as a trial participating centre.
28/09/2022: The recruitment start date has been changed from 01/09/2022 to 01/11/2022.
04/08/2022: Trial's existence confirmed by Wales Research Ethics Committee 3.
