Clinical trial NCT03367910: Fecal Microbiota Transplantation (FMT) for MDRO UTI
Official title: Fecal Microbiota Transplantation Using RBX2660 for the Prevention of Recurrent Urinary Tract Infections Due to Multidrug Resistant Organisms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Urinary Tract Infections
Keywords: Urinary tract infection
Multidrug resistant organism
Fecal microbiota transplantation
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
name: University of Pennsylvania
name: Duke University
name: Rush University
name: Rebiotix Inc.
First posted: 2017-12-11
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Participants with eligible MDRO UTIs will receive FMT.
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients With Adverse Events During and After FMT
timeFrame: Six months post-FMT
Secondary outcomes:
measure: Number of Patients With Recurrent UTI Post-FMT
timeFrame: Six months post-FMT
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Erik Dubberke, MD, MSPH
role: PRINCIPAL_INVESTIGATOR
References: