Autologous Fecal Microbiota Transplantation to Prevent Antibiotic Resistant Bacteria Colonization (RACE)

Randomized Controlled Trial of Autologous Microbiome Reconstitution to Prevent Colonization by Antibiotic rEsistant Bacteria

This study, a Randomized controlled trial of Autologous microbiome reconstitution to prevent Colonization by antibiotic rEsistant bacteria (RACE), seeks to investigate the safety, feasibility and the role of autologous fecal microbiota transplantation (FMT) for the prevention of antibiotic resistant bacteria (ARB) through microbiome restoration.

Study Overview

• Status: Completed
• Conditions: Antibiotic Resistant Strain
• Intervention / Treatment: Biological: Autologous fecal microbiota transplant (Auto-FMP Enema); Other: Placebo Enema Preparation

Detailed Description

Note: The Protocol and Statistical Analysis Plan document contains modifications from what is on file at the FDA to reflect redactions and formatting requirements for public posting on ClinicalTrials.gov

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University - Boston Medical Center nursing home consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria for study enrollment

1. Long-term care residents associated with Boston University-Boston Medical Center nursing home consortium
2. Adults (18 years or older)

Inclusion criteria for randomization

1) Infection requiring antimicrobial treatment at the discretion of the treating physician

Exclusion criteria for study enrollment

1. Pregnant. Participants of childbearing age will undergo urine pregnancy testing
2. Participant or substitute decision maker unable to provide informed consent
3. Allergies to following ingredients generally recognized as safe: glycerol and sodium chloride
4. Current enrollment in hospice
5. Colostomy
6. Unable to adhere to protocol requirements
7. Any condition that the physician investigators deems unsafe, including other conditions or medications that the investigator determines puts the participant at greater risk from FMT
8. Recent travel (last six months) to high risk regions based on the International SOS Medical Risk Rating system
9. Recent exposure (last six months) to unsafe drinking water

Exclusion criteria for stool collection

Enrollment stool sample will be tested for ARBs and processed into autologous FMT treatment (if of qualifying size). Sample will not be collected if any of the following are true:

1. Oral or intravenous antibiotic exposure within the previous 6 weeks of stool collection date (topical antibiotics will be permitted)
2. Active gastrointestinal infection at stool collection
3. Fever at the time of stool collection
4. Currently ill or complaining of any of the following signs or symptoms of illness: fever, diarrhea, blood stools and/or vomiting
5. Participants with a history of gastrointestinal (GI) illness within the past 30 days prior to enrollment stool collection, that at the discretion of the site investigator could reasonably be caused by one of the following pathogens: 1) Vibrio spp. 2) Norovirus 3) Rotovirus 4) Adenovirus 5) Shiga toxin

Exclusion criteria for randomization

• Colonized with CRE (assessed by PCR or culture assay during enrollment phase)
• Colonized with VRE (assessed by PCR or culture assay during enrollment phase)
• Colonized with ESBL (assessed by PCR or culture assay during enrollment phase)
• Colonized with CDI (assessed by EIA assay on stool collected at enrollment phase)
• Treatment with antibiotics which are active against MRSA (i.e. vancomycin or linezolid) prior to randomization to FMT intervention or placebo.
• Stool culture positive for common enteric pathogens (Salmonella spp., Shigella spp., Campylobacter spp.)
• Participants who develop a GI illness with symptoms such as (but not limited to) vomiting or diarrhea within 30 days after collection of enrollment stool will be evaluated by the site investigator. If the site investigator determines that the symptoms were most likely caused by 1) Vibrio spp., 2) Norovirus, 3) Rotavirus, 4) Adenovirus, or 5) Shiga toxin, the enrollment stool will be sent out to test for these organisms. If the culture is positive for any of these organisms, the participant will be excluded from randomization
• Any condition that the physician investigators deems unsafe, including other conditions or medications that the investigator determines puts the participant at greater risk from FMT
• Participants who become severely immunocompromised, as defined by the investigator or treating physician, will be excluded prior to receiving intervention

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (autologous fecal microbiota preparation); Participants randomized into the treatment arm will receive a single dose of autologous fecal microbiota preparation (auto-FMP) via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. Route of Administration: Enema Dosing Regimen: 125mL x 1 dose	Biological: Autologous fecal microbiota transplant (Auto-FMP Enema); FMT is the process by which processed donor microbiota material is transplanted into recipients. The aim is to reconstitute the normal intestinal microbial flora in recipients. In this study, the fecal microbiota preparation will be made from the participant's own stool and processed into an auto-FMP enema formulation.
Placebo Comparator: Placebo; Participants randomized to the placebo arm will receive a single dose of placebo FMT via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms.	Other: Placebo Enema Preparation; The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (NIH Grade ≥2) at Day 7 After Randomization	Number of participants with NIH Grade ≥2 adverse events at Day 7 after randomization.	Day 7 after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Clearance of Antibiotic Resistant Bacteria (ARB)	Number of patients with clearance of ARB among patients colonized at Day 28 by Polymerase Chain Reaction (PCR) assay or culture-based assay. ARBs are: Carbapenem-resistant Enterobacteriaceae (CRE) by PCR or culture assay, Extended spectrum beta-lactamase (ESBL)-producing organisms by PCR or culture assay, Vancomycin-resistant enterococci (VRE) by PCR or culture assay, or Clostridium difficile by PCR	Day 28 after randomization
Number of Participants Who Develop Any ARB-associated Infections	Number of participants who develop any ARB-associated infections following autologous FMT at Day 3, Day 7, Day 28, and Month 6	Day 3, Day 7, Day 28, Month 6
Number of Participants With NIH Grade ≥2 AEs at Day 28 and Month 6	Number of participants with NIH Grade ≥2 adverse events (intermediate at Day 28 and long-term at Month 6) following autologous FMT.	Day 28, Month 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiome Disruption Indices (MDI) (16S rRNA Sequencing)	MDI-community and MDI-species at baseline (pre-infection on the date of stool collection), post-antibiotics on the intervention/placebo date (Day 0, Day 3, Day 7, and Day 28)	Day 0, Day 3, Day 7, Day 28

Collaborators and Investigators

• Sponsor: Microbiome Health Research Institute
• Collaborators: Boston Medical Center
• Investigators: Principal Investigator: Majdi Osman, MD, MPH, Microbiome Health Research Institute, (d/b/a OpenBiome)

Publications and helpful links

General Publications

• Liu CK, Seo J, Pravodelov V, Frazier S, Guy M, Concilio K, Lau-Ng R, Brandeis G, Watson J, van der Velde J, Olesen SW, Budree S, Njenga M, Kassam Z, Osman M. Pilot study of autologous fecal microbiota transplants in nursing home residents: Feasibility and safety. Contemp Clin Trials Commun. 2022 Mar 7;27:100906. doi: 10.1016/j.conctc.2022.100906. eCollection 2022 Jun.

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2017
• Primary Completion (Actual): December 19, 2018
• Study Completion (Actual): June 18, 2019

Study Registration Dates

• First Submitted: February 17, 2017
• First Submitted That Met QC Criteria: February 21, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): May 5, 2021
• Last Update Submitted That Met QC Criteria: April 13, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Autologous Fecal Microbiota Transplantation
• Additional Relevant MeSH Terms: Wounds and Injuries; Sprains and Strains
• Other Study ID Numbers: 200201691946

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