Fecal Microbiota Transplantation (FMT) for MDRO UTI

Fecal Microbiota Transplantation Using RBX2660 for the Prevention of Recurrent Urinary Tract Infections Due to Multidrug Resistant Organisms

The purpose of this study is to determine the safety and impact of fecal microbiota transplantation (FMT) on the fecal and urine microbiome, urine metabolome, risk of recurrent urinary tract infection (UTI), and persistent multidrug resistant organism (MDRO) colonization of patients with a history of recurrent MDRO UTIs. This is an open label phase 1-2 study.

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infections
• Intervention / Treatment: Drug: Fecal microbiota transplant

Detailed Description

Multidrug resistant organism (MDRO) infections are increasingly common. The most common type of infection caused by MDROs is urinary tract infections (UTIs). Many MDROs are inhabitants of the colon, and MDROs can contaminate the periurethral area and migrate to the bladder. Patients with MDRO UTI frequently experience multiple relapses and hospitalizations, which both increase the individual's morbidity and mortality and leads to additional MDRO nosocomial spread. There are few options available to prevent MDRO UTIs, and there are limited strategies to identify patients at risk for recurrent MDRO UTI and prevent or reverse MDRO colonization. A potential novel method to reverse MDRO colonization and prevent recurrent UTI would be by repopulating the gut microbiome with "healthy" microbiota by fecal microbiota transplantation (FMT).

In this study, participants with a history of severe, recurrent MDRO UTI will receive FMT. Participants will submit stool and urine specimens pre- and post-FMT, and the effect of FMT on the participants' fecal and urine microbiome, urine metabolome, persistent MDRO colonization, and risk of recurrent UTI will be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University

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:

• Age ≥18 years old.
• Outpatient status at time of FMT.
• History of at least three recurrent UTIs due to an MDRO; at least two recurrent, severe infections due to MDRO requiring hospitalization; or at least two recurrent infections due to MDRO for which only antimicrobials with rate limiting toxicities (see above) are available.
• Be without active infection due to the MDRO at the time of FMT.
• Not be receiving antimicrobials (therapeutic or suppressive) within 48 hours of FMT.

Exclusion Criteria:

• Age <18 years
• Inpatient status at time of FMT
• Ineligible UTI
• >1 organism in urine (other than minimal contaminants)
• Decline to participate
• Recurrent Clostridium difficile infection
• Presence of intra-abdominal devises
• Neutropenia (ANC <500 mm3)
• Intestinal mucosal disruption
• Unlikely to survive 6 months
• Pregnancy or unwillingness to use contraceptives
• Short gut syndrome
• Use of medications that affect intestinal motility
• Gastrointestinal motility disorder
• Inflammatory bowel disease
• Recent abdominal surgery
• Active typhlitis
• Active diverticulitis
• Current gastrointestinal graft versus host disease
• HIV with lack of antiretroviral therapy (ART)
• CD4 count <200 mm3
• Peritoneal dialysis
• Cirrhosis with ascites
• Active intra-abdominal malignancy
• Presence of chronic indwelling foley catheter, chronic suprapubic catheter, or ileal conduit
• Active hepatitis C
• Active hepatitis B
• Presence of ureteral stent
• Active kidney stone that is believed to be a persistent source of bacterial colonization
• Any condition where the investigator feels the risks of FMT outweigh the benefits

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: FMT for MDRO UTI; Participants with eligible MDRO UTIs will receive FMT (150mL of RBX2660) via enema.	Drug: Fecal microbiota transplant; 150mL of FMT product RBX2660 delivered via enema; Other Names: Stool transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Adverse Events During and After FMT	The number, types, severity, and relation of adverse events to study procedures or product will be analyzed.	Six months post-FMT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Recurrent UTI Post-FMT	Risk of recurrent UTI post-FMT will be evaluated	Six months post-FMT

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: University of Pennsylvania; Duke University; Centers for Disease Control and Prevention; Rush University; Rebiotix Inc.
• Investigators: Principal Investigator: Erik Dubberke, MD, MSPH, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 8, 2018
• Primary Completion (ACTUAL): December 31, 2021
• Study Completion (ACTUAL): December 31, 2021

Study Registration Dates

• First Submitted: December 5, 2017
• First Submitted That Met QC Criteria: December 5, 2017
• First Posted (ACTUAL): December 11, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 18, 2022
• Last Update Submitted That Met QC Criteria: March 9, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Urinary tract infection; Fecal microbiota transplantation; Multidrug resistant organism
• Additional Relevant MeSH Terms: Urologic Diseases; Infections; Urinary Tract Infections
• Other Study ID Numbers: 201708204

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