Ashwagandha (Withania somnifera (L.) Dunal) for promoting recovery in long covid: protocol for a randomised placebo-controlled clinical trial (APRIL Trial)
Kamlesh Khunti,
Shailen Sutaria,
Poppy Alice Carson Mallinson,
Sanjay Kinra,
Rohini Mathur,
Anoop SV Shah,
Tim Clayton,
Judith Lieber,
Alexander Perkins,
Shereen Allaham,
Nick Birk,
Lily Hopkins,
Manisha Joshi,
Mahesh Mathpathi,
Arandeep Dhillon,
Sidra S Beg,
Archie Khan,
Vanessa TW Kam,
Galib R,
S Rajagopala,
Amarjeet Bhamra,
Geetha Krishnan G Pillai,
Tanuja Nesari
Affiliations
Kamlesh Khunti
Diabetes Research Centre, University of Leicester, Leicester, UK
Shailen Sutaria
Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
Poppy Alice Carson Mallinson
Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
Sanjay Kinra
Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
Rohini Mathur
Centre for Primary Care and Public Health, Queen Mary University of London Wolfson Institute of Population Health, London, UK
Anoop SV Shah
Centre for Global Chronic Conditions, Faculty of Epidemiology and Population Health, Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
Tim Clayton
Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK
Judith Lieber
Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK
Alexander Perkins
Centre for Global Chronic Conditions, Faculty of Epidemiology and Population Health, Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
Shereen Allaham
Department of Epidemiology and Public Health, UCL, London, UK
Nick Birk
Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
Lily Hopkins
Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
Manisha Joshi
Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
Mahesh Mathpathi
Department of Global Health and Development, London School of Hygiene & Tropical Medicine, London, UK
Arandeep Dhillon
Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
Sidra S Beg
The University of Texas Health Science Center at Houston, Houston, Texas, USA
Archie Khan
Department of Infection Biology, London School of Hygiene & Tropical Medicine, London, UK
Vanessa TW Kam
Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
Galib R
All India Institute of Ayurveda, New Delhi, New Delhi, India
S Rajagopala
All India Institute of Ayurveda, New Delhi, New Delhi, India
Amarjeet Bhamra
All-Party Parliamentary Group on Indian Traditional Sciences, London, UK
Geetha Krishnan G Pillai
World Health Organization, Geneva, Switzerland
Tanuja Nesari
All India Institute of Ayurveda, New Delhi, New Delhi, India
Background Long covid describes a syndrome of persistent symptoms following COVID-19 and is responsible for substantial healthcare and economic burden. Currently, no effective treatments have been established. Ashwagandha (Withania somnifera (L.) Dunal) is a medicinal herb traditionally used in India for its immune-strengthening and anti-inflammatory properties. Withanolides, a family of steroid-derived molecules unique to Ashwagandha, have been shown to modulate inflammatory pathways in animal models, and several small randomised trials in humans support its effectiveness for reducing symptoms that are also associated with long covid. Therefore, this study aims to assess whether Ashwagandha is effective and safe for improving functional status and reducing symptom burden in adults living with long covid.Methods A randomised double-blind placebo-controlled trial will be performed at participating general practice (GP) surgeries and long covid clinics across the UK. Individuals diagnosed with long covid will be screened for eligibility and then randomised 1:1 to take 1000 mg daily of Ashwagandha root extract tablets (standardised to <0.9% withanolides) or matching placebo tablets for 3 months (target, n = 2500). Monthly online surveys will be performed to collect patient-reported outcomes, and monthly safety monitoring, including liver function tests, will be conducted by clinical site teams. The primary outcome of the Post-COVID Functional Status Scale score at 3 months will be assessed by baseline-adjusted ordinal logistic regression, according to a pre-published statistical analysis plan. The secondary outcomes included validated quality of life and long covid symptom scales, work status and productivity and adverse events. The trial has been approved as a Clinical Trial of an Investigational Medicinal Produce by the Medicines and Healthcare Regulatory Authority and by the NHS Research Ethics Committee and Health Research Authority.Discussion Treatments for long covid are urgently needed. This trial will robustly evaluate the safety and efficacy of a candidate treatment with a promising efficacy and safety profile. If found to be effective, the findings will likely influence treatment guidelines and improve health outcomes in those living with long covid.Trial registration number This trial was pre-registered on 15/08/2022: ISRCTN12368131