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

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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1136/bmjopen-2020-047069

Publication Info

Tang, Helen, Lauren Bohannon, Meagan Lew, David Jensen, Sin-Ho Jung, Aaron Zhao, Anthony D Sung, Paul E Wischmeyer, et al. (2021). Randomised, double-blind, placebo-controlled trial of Probiotics To Eliminate COVID-19 Transmission in Exposed Household Contacts (PROTECT-EHC): a clinical trial protocol. BMJ open, 11(5). p. e047069. 10.1136/bmjopen-2020-047069 Retrieved from https://hdl.handle.net/10161/23215.

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Scholars@Duke

Jung

Sin-Ho Jung

Professor of Biostatistics & Bioinformatics

Design of Clinical Trials
Survival Analysis
Longitudinal Data Analysis
Clustered Data Analysis
ROC Curve Analysis
Design and Analysis of Microarray Studies
Big Data Analysis

Sung

Anthony D Sung

Adjunct Associate Professor of Medicine

I am dedicated to the treatment of hematologic malignancies through cellular therapies such as hematopoietic stem cell transplantation (HCT). My research focuses on strategies to reduce complications of HCT and ranges from preclinical studies using murine models of HCT to Phase 1 and Phase 2 clinical trials. Areas of interest include the role of the microbiota (the trillions of bacteria living in and on our bodies), nutrition, and exercise in modulating HCT outcomes such as graft-versus-host disease (GVHD) and infections. In addition to advancing new pharmacological and cellular immunotherapies in support of these goals, we also are developing mobile health technologies (mHealth) to monitor patients at home, both as part of our innovative home transplant program as well as to improve follow up care of all our patients when they return home after transplant.

Wischmeyer

Paul Edmund Wischmeyer

Professor of Anesthesiology

Paul Wischmeyer M.D., EDIC, FASPEN, FCCM is a nutrition, exercise, critical care, and perioperative  physician-researcher who specializes in enhancing preparation and recovery from surgery, critical care and COVID-19. He serves as a Tenured Professor of Anesthesiology and Surgery at Duke. He also serves as the Associate Vice Chair for Clinical Research in the Dept. of Anesthesiology and Director of the TPN/Nutrition Team at Duke. Dr. Wischmeyer earned his medical degree with honors at The University of Chicago Pritzker School of Medicine, where he was elected into the honor society of Alpha Omega Alpha for outstanding academic achievement. He completed his pediatric internship at University of Colorado Children’s Hospital and his anesthesiology/critical care residency training at the University of Chicago. He also completed a Clinical Pharmacology fellowship and the NIH K30 Clinical Research Scientist Training Program while at University of Chicago.
   Dr. Wischmeyer’s clinical and research focus is in critical care, perioperative care exercise, and nutrition to help patients prepare and recover from illness and surgery. His research interests include surgical and ICU nutrition and exercise rehabilitation; role of parenteral, enteral, and oral nutrition to improve patient outcomes; perioperative optimization; post-illness muscle mass and functional recovery; and probiotics/microbiome. His research interests have also recently been focused on COVID-19 research into COVID-19 metabolism, role of probiotics in COVID19 prevention and treatment, and exercise and nutrition programs to recover from COVID-19 and Long COVID-19. Dr. Wischmeyer’s research group has been awarded multiple NIH, DOD, and other peer reviewed grants to perform research ranging from basic mechanistic cell work to large-scale multi-center clinical trials in the fields of critical care, perioperative medicine, nutrition, illness metabolism, microbiome/probiotics, and exercise interventions to improve functional outcomes. For his research work and clinical work, Dr. Wischmeyer has received numerous awards from national and international societies including, The Jeffrey Silverstein Award and Memorial Lecture for Humanism in Medicine from the American Delirium Society, The John M. Kinney Award for the most significant contribution to field of general nutrition, the Stanley Dudrick Research Scholar Award by the American Society for Parenteral and Enteral Nutrition and The Lifetime Achievement Award of the International Parenteral Nutrition Society (IPENEMA) for significant contributions to the field of nutrition.  Dr. Wischmeyer has over 200 peer-reviewed publications in critical care, anesthesiology, and nutrition, including in the New England Journal of Medicine. Finally, he has been an invited speaker at numerous national and international medical meetings delivering over 900 invited presentations over his career. He has an H-index of 73 with over 16,500 citations to his work, including 1 publication with > 1000 citations and 55 publications with > 100 citations. He is also the founder and director of the Duke Online Clinical Nutrition Fellowship, an international fellowship to provide clinical nutrition training to healthcare providers worldwide, as well as unique scholarship opportunities for healthcare providers in developing nations.
    Dr. Wischmeyer passion for helping patients recover from illness and surgery arises from his personal experiences as both doctor and patient in the ICU. Dr. Wischmeyer has undergone over 27 major surgeries and personally experienced multiple ICU stays due to a childhood GI illness that took more than half of his intestinal tract. Thus, preparation for surgery/critical care and recovery from illness are a way of life for Dr. Wischmeyer that he is passionate about teaching his patients and other caregivers worldwide.

 


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