Randomized, Double Blind, Placebo Controlled, Clinical Trial to Study Ashwagandha Administration in Participants Vaccinated Against COVID-19 on Safety, Immunogenicity, and Protection With COVID-19 Vaccine–A Study Protocol

Abstract

IntroductionVaccines have emerged as the most effective tool in the fight against COVID-19. Governments all over the world have rolled out the COVID-19 vaccine program for their populations. Oxford-AstraZeneca COVID-19 vaccine (COVISHIELD™) is widely used in India. A large number of Indian people have been consuming various traditional medicines in the hope of better protection against COVID-19 infection. Several studies have reported immunological benefits of Withania somnifera (Ashwagandha) and its potential as a vaccine adjuvant. We propose to study the safety, immunogenicity and clinical protection offered by a 6-month regimen of Ashwagandha in participants who volunteer to be vaccinated against COVID-19 (COVISHIELDTM) in the ongoing national program of vaccination.Methods and AnalysisWe designed a prospective, randomized, double-blind, parallel-group, placebo-controlled, two-arm, exploratory study on healthy volunteers receiving the COVISHIELDTM vaccine. The administration of Ashwagandha will begin within 7 days of the first or second dose of COVISHIELDTM. Primary outcome measure is immunogenicity as measured by SARS-CoV-2 spike (S1) and RBD-specific IgG antibody titres. Secondary outcome measures are safety, protective immune response and quality of life measures. All adverse events will be monitored at each time throughout the study. Participants will be tracked on a daily basis with a user-friendly mobile phone application. Following power calculation 600 participants will be recruited per arm to demonstrate superiority by a margin of 7% with 80% power. Study duration is 28 weeks with interim analysis at the end of 12 weeks.Ethics and DisseminationEthics approval was obtained through the Central and Institutional Ethics Committees. Participant recruitment commenced in December 2021. Results will be presented in conferences and published in preprints followed by peer-reviewed medical journals.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [CTRI/2021/06/034496].

In vitro effect of Withania somnifera, AYUSH-64, and remdesivir on the activity of CYP-450 enzymes: Implications for possible herb−drug interactions in the management of COVID-19

“…Indeed, it is possible that these two together might compete with each other and exhibit moderate inhibition of CYP2C8 activity. Interestingly, there was no mention of any significant interaction or adverse reaction during the clinical studies conducted with ashwagandha and AYUSH-64 ( Gundeti et al, 2020a ; Reddy et al, 2020 ; Chopra et al, 2021 ; Chopra et al, 2022 ; Singh et al, 2022 ). The HDIs and pharmacokinetic parameters presented in the current study provide insights into having safer therapeutic options for mitigating SARS-CoV-2 as well as their use for the treatment of chronic diseases.…”

Phytocompositions of ayurvedic medicine in the restoration of menstrual health in women of early reproductive age who have survived moderate and severe form of COVID-19

“…The organ-preserving results of Withania somnifera are used to reduce systemic inflammation, which protects against the severity of inflammation-induced organ damage. In addition to these antiviral actions, Bethany has a confirmed sedative role in supporting mental health, which may be very useful in the control and treatment of COVID-19 [80]. Since the interaction of SARS-CoV-2 S-protein RBD and ACE2 receptor is very important for viral entry into host cells during infection, thus bioactive compounds of Withania somnifera such as withanone and withaferin A may be involved in the management and treatment of COVID-19 [81].…”

Withania somnifera (L.) Dunal (Ashwagandha) for the possible therapeutics and clinical management of SARS-CoV-2 infection: Plant-based drug discovery and targeted therapy

“…However, there were some adverse reactions reported in people due to prior allergies ( Sumito et al., 2021 ). Although Withania somnifera cannot fully eradicate SARS-CoV-2, studies have shown that co-administration of Ashwagandha with the COVISHIELD™ vaccine enhanced the antibody titers, particularly after the first dose of the vaccine ( Chopra et al., 2022 ).…”