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

  1. Arvind Chopra
  2. Preeti Chavan-Gautam
  3. Girish Tillu
  4. Manjit Saluja
  5. Swapnil Borse
  6. Sanjeev Sarmukaddam
  7. Susmita Chaudhuri
  8. BCS Rao
  9. Babita Yadav
  10. Narayanam Srikanth
  11. Bhushan Patwardhan

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Abstract

Vaccines 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 (COVISHIELD TM ) in the ongoing national program of vaccination.

Methods and Analysis

We designed a prospective, randomized, double-blind, parallel-group, placebo-controlled, two-arm, exploratory study on healthy volunteers receiving the COVISHIELD TM 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 Dissemination

Ethics 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].

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  1. Version published to 10.3389/fmed.2022.761655
  2. ScreenIT

    SciScore for 10.1101/2021.07.02.21259886: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: The investigator will be responsible for obtaining written informed consent from each participant prior to screening as per the national ethics guidelines [19].
    IACUC: The investigator will be responsible for obtaining written informed consent from each participant prior to screening as per the national ethics guidelines [19].
    IRB: Serious adverse events will require immediate reporting by the study investigator to the Sponsor and Ethics Committee, within 24 hours, of becoming aware of the SAE.
    Sex as a biological variableEligibility: Inclusion criteria: Apparently healthy adults of either sex aged 18-45 years; SARS-COV-2 RT-PCR negative tested volunteers and eligible for vaccination; Written informed consent by the participants; Willing to comply with study protocol requirements; Female participants of childbearing potential with a negative urine pregnancy test carried out within 24 hours prior to study vaccine administration or should be classified as non-childbearing potential (defined as surgically sterile or post-menopausal); Women with a child bearing potential shall continue adequate contraception (Barrier or hormonal) throughout the duration of the study.
    RandomizationStudy design: This will be a prospective, randomized, double blind, parallel group, placebo controlled, multicentric study on healthy volunteers receiving the COVISHIELD™ vaccine with a superiority design.
    BlindingStudy design: This will be a prospective, randomized, double blind, parallel group, placebo controlled, multicentric study on healthy volunteers receiving the COVISHIELD™ vaccine with a superiority design.
    Power AnalysisThe sample size was the calculated with 80% power and after consideration of interim analysis at the end of 12 weeks; assuming vaccine efficacy of 80% [24].

    Table 2: Resources

    Antibodies
    SentencesResources
    Clinical outcomes: Primary Outcome Measure: Immunogenicity as measured by SARS-CoV-2 spike (S1) and RBD-specific IgG antibody titres.
    RBD-specific IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    All statistical processing will be performed using standard statistical package (SPSS, BMDP, and CIA) unless otherwise stated.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.07.02.21259886v1 on medRxiv