Randomised, double-blind, placebo-controlled trial of Probiotics To Eliminate COVID-19 Transmission in Exposed Household Contacts (PROTECT-EHC): a clinical trial protocol

Helen Tang, Lauren Bohannon, Meagan Lew, David Jensen, Sin-Ho Jung, Aaron Zhao, Anthony D Sung, Paul E Wischmeyer, Helen Tang, Lauren Bohannon, Meagan Lew, David Jensen, Sin-Ho Jung, Aaron Zhao, Anthony D Sung, Paul E Wischmeyer

Abstract

Introduction: The COVID-19 pandemic has proven to be an unprecedented challenge to worldwide health, and strategies to mitigate the spread and severity of COVID-19 infection are urgently needed. Emerging evidence suggests that the composition of the gut microbiome and modification of microbial ecology via probiotics can affect susceptibility to a wide range of infections, including respiratory tract infections. In this study, we aim to evaluate the effects of the probiotic Lactobacillus rhamnosus GG (LGG) versus placebo on COVID-19 infection status and the gut microbiome in subjects with a household contact who has tested positive for COVID-19.

Methods and analysis: In this double-blinded, randomised, placebo-controlled trial, we will randomise 1132 subjects having a household contact who has recently (≤7 days) tested positive for COVID-19 to daily oral LGG or placebo for 28 days. We hypothesise that taking LGG as a probiotic will protect against COVID-19 infection and reduce the severity of disease in those who become infected (primary endpoint: decreased symptoms), and will be associated with beneficial changes in the composition of the gut microbiome. Stool samples and nasal swabs will be collected to evaluate the microbiome by 16S rRNA sequencing and the presence of SARS-CoV-2 by PCR, respectively. We will also conduct multivariate analysis of demographic, behavioural, temporal, and other variables that may predict development of symptoms and other outcomes.

Ethics and dissemination: This trial is conducted under a Food and Drug Administration Investigational New Drug for LGG, has received ethics approval by the institutional review board of Duke University and enrolment has begun. We plan to disseminate the results in peer-reviewed journals and at national and international conferences.

Trial registration number: NCT04399252.

Keywords: COVID-19; clinical trials; gastroenterology; infectious diseases; microbiology; public health.

Conflict of interest statement

Competing interests: iHealth has provided unrestricted gift funding donation to support probiotic research in COVID-19 to PEW and ADS.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study design and timeline. Adh, adherence to treatment; C19R, COVID-19-related event reporting; D, demographics; EHx, exposure history; HRF, household risk factors; LGG, Lactobacillus rhamnosus GG; Meds, medications; MHx, medical history; Sx/AE, symptoms/adverse events.

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