Randomized, double blind, placebo controlled, clinical trial to study co-administration of Ashwagandha on safety, immunogenicity, and protection with COVID-19 vaccine: A Study Protocol

ABSTRACT

IntroductionThe government of India has rolled out COVID-19 vaccine program for individuals who are 18 years of age and above and priority is being given to the elderly, and individuals with morbidity. Oxford-AstraZeneca COVID-19 vaccine (COVISHIELD) is most 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 Ashwagandha and its potential as vaccine adjuvant. We plan to study co-administration of Ashwagandha with COVISHIELD vaccine on safety, immunogenicity and protection. Methods and analysisWe designed a prospective, randomized, double blind, parallel group, placebo controlled, two arm, exploratory study on healthy volunteers receiving the COVISHIELD vaccine. In addition to the two dose schedule of COVISHIELD vaccine as per national guidelines, participants will be administered 8gm Ashwagandha or placebo tablets respectively per day. 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. Adverse event following immunization 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 disseminationEthical approval was obtained through the Central and institutional Ethics Committees. Participant recruitment is expected to commence by August 2021. Results will be presented in conferences and published in preprint followed by peer-reviewed medical journals. Registration detailsClinical Trial Registry - India (CTRI) Registration Number CTRI/2021/06/034496. Date of Registration June 30, 2021. Strengths and limitations of this studyO_LINovel study to demonstrate effect of coadministration of immune adjuvant and COVID-19 vaccine on safety and immunogenicity. C_LIO_LIRandomised placebo controlled 28 weeks study with 80 percent power to demonstrate role of putative natural immunomodulator to augment the protection and reduce breakthrough infections C_LIO_LIState of art immune assays to measure specific antibodies to SARS-CoV-2 to demonstrate both persistent and late upsurge in immune response C_LIO_LIDaily tracking of participants using a study specific designed mobile app C_LIO_LIAn interim analysis is planned to provide information on early immune response after first dose of vaccine C_LIO_LIParticipants may be reluctant to donate blood repeatedly for immune assays; compliance with the test drug may be a challenge; asymptomatic infections may be missed; the study is not measuring cellular immune response. C_LI