Effect of Lactobacillus on the Microbiome of Household Contacts Exposed to COVID-19

A Randomized Trial of the Effect of Lactobacillus on the Microbiome of Household Contacts Exposed to COVID-19

The purpose of this study is to evaluate the effect of the probiotic Lactobacillus rhamnosus GG (LGG) and the effect of COVID-19 on the microbiome (the microorganisms that live in and on the human body) in exposed household contacts of COVID-19. This is a randomized, double-blind, placebo-controlled study, meaning subjects will be randomly assigned to receive LGG or a placebo (an inactive substance given in the same form as the active substance) and will not know which product they are receiving. Subjects will participate in the study for around 60 days. All subjects must refrain from taking any other probiotics while on study. All subjects must have access to e-mail and the internet to complete study questionnaires. Participation in this study entails taking LGG/placebo for 28 days, responding to questionnaires, and providing stool and nasal swab samples.

Study Overview

• Status: Completed
• Conditions: Microbiome
• Intervention / Treatment: Dietary supplement: Lactobacillus rhamnosus GG; Dietary supplement: Lactobacillus rhamnosus GG Placebo

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age >=1 year (as children <1 year may not be able to take oral probiotics)
• Household contact of someone diagnosed with COVID-19
• Willingness to stop taking other probiotics or to not take any other probiotic while on LGG/placebo (taking a probiotic at the time of screening will not be considered a reason for exclusion. However, subjects will be asked to stop taking their probiotic if they enroll on the study).
• Access to e-mail/internet to complete electronic consent via REDCap

Exclusion Criteria:

• Symptoms of COVID-19 at enrollment, including:

  • Fever
  • Respiratory symptoms
  • GI symptoms
  • Anosmia
  • Ageusia ->7 days since original patient associated with household contact was diagnosed with COVID-19
• Taking hydroxychloroquine or remdesivir for any reason (as this would have the potential to decrease the expected rate of COVID-19 in this population and affect our power and sample size calculations)
• Enrolled in a COVID-19 prophylaxis study (as this would have the potential to decrease the expected rate of COVID-19 in this population and affect our power and sample size calculations)

• Any medical condition that would prevent taking oral probiotics or increase risks associated with probiotics including but not limited to:

  • Inability to swallow/aspiration risk and no other methods of delivery (e.g., no G/J tube)

  • Increased infection risk due to immunosuppression due to:

    • Chronic immunosuppressive medication
    • Prior organ or hematopoietic stem cell transplant
    • Known neutropenia (ANC <500 cells/ul)
    • HIV and CD4 <200 cells/ul

  • Increased infection risk due to endovascular due to:

    • Rheumatic heart disease
    • Congenital heart defect,
    • Mechanical heart valves
    • Endocarditis
    • Endovascular grafts
    • Permanent endovascular devices such as permanent (not short-term) hemodialysis catheters, pacemakers, or defibrillators

  • Increased infection risk due to mucosal gastrointestinal due to:

    • Gastroesophageal or intestinal injury, including active bleeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LGG Arm; Participants in this arm will be given LGG for 28 days.	Dietary supplement: Lactobacillus rhamnosus GG; Participants will take 2 capsules per day of either LGG or placebo.
Placebo Comparator: Placebo; Participants in this arm will be given a placebo for 28 days.	Dietary supplement: Lactobacillus rhamnosus GG Placebo; Participants will take 2 capsules per day of LGG placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of one or more symptoms of COVID-19 during the study period	Incidence of one or more symptoms of COVID-19 (fever, chills, headache, muscle aches, runny nose, sore throat, cough, shortness of breath, nausea or vomiting, diarrhea, stomach upset or pain, excessive bloating or gas, constipation, loss of sense of smell, loss of sense of taste, rash, painful toes, or other symptoms related to COVID-19 diagnosis) during the study period	60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of laboratory-confirmed COVID-19 during the study period	Incidence of laboratory-confirmed COVID-19 (all based on medically-dictated, clinical testing and electronic medical record review) or research laboratory-confirmed COVID-19 (all, based on research testing of nasal swab and stool samples) during the study period	60 days
Complications of COVID-19	Complications of COVID-19 (e.g., need for hospitalization, intubation, mortality) during the study period	60 days
Types of symptoms of COVID-19	Types of symptoms of COVID-19 during the study period (e.g., fever, chills, headache, muscle aches, runny nose, sore throat, cough, shortness of breath, nausea or vomiting, diarrhea, stomach upset or pain, excessive bloating or gas, constipation, loss of sense of smell, loss of sense of taste, rash, painful toes, or other symptoms related to COVID-19 diagnosis)	60 days
Duration of symptoms of COVID-19	Duration of symptoms (days) of COVID-19 during the study period	60 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Shannon Diversity in patients that develop COVID-19	Impact of COVID-19 on and of the microbiome, as determined by Shannon Diversity of stool and nasal swab samples, during the study period	Baseline, Day 7, Day 28

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Anthony Sung, MD, Duke University; Principal Investigator: Paul Wischmeyer, MD, Duke University

Publications and helpful links

General Publications

• Tang H, Bohannon L, Lew M, Jensen D, Jung SH, Zhao A, Sung AD, Wischmeyer PE. 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. 2021 May 5;11(5):e047069. doi: 10.1136/bmjopen-2020-047069.

Helpful Links

• Pre-print: Daily Lactobacillus Probiotic versus Placebo in COVID-19-Exposed Household Contacts (PROTECT-EHC): A Randomized Clinical Trial

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2020
• Primary Completion (Actual): July 8, 2021
• Study Completion (Actual): July 8, 2021

Study Registration Dates

• First Submitted: May 19, 2020
• First Submitted That Met QC Criteria: May 21, 2020
• First Posted (Actual): May 22, 2020

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19; Lactobacillus rhmanosus GG
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: Pro00105674

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No