Efficacy and Safety of Fecal Microbiota Transfer (FMT) for Recurrent Urinary Tract Infections in Women

Phase 2CompletedNCT07194941

Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal40 enrolled

Overview

Urinary tract infections (UTIs) are highly prevalent worldwide, especially in women, with frequent recurrences and significant healthcare costs. The proposed Phase II clinical trial will define dosing and administration strategies for FMT in recurrent UTIs. If effective, this ecological approach could provide a novel therapeutic alternative to antibiotics for one of the most common infectious diseases worldwide

Urinary tract infections (UTIs) are highly prevalent worldwide, especially in women, with frequent recurrences and significant healthcare costs. Current treatment relies mainly on antibiotics, which contribute to antimicrobial resistance and adverse effects. While preventive strategies such as antibiotic prophylaxis, personalized vaccines, D-mannose, or hyaluronic acid instillations have been explored, they show limited success, partly because the intestinal tract acts as the reservoir for uropathogens. This project proposes fecal microbiota transplantation (FMT) from healthy donors to modify the intestinal microbiome of patients with recurrent UTIs, aiming to eradicate intestinal colonization by resistant pathogens and prevent urinary infections. FMT, already approved for recurrent Clostridioides difficile since 2015, has evolved from colonoscopy-based procedures to oral capsules. Observations in clinical practice suggest FMT may incidentally clear recurrent UTIs and multidrug-resistant bacteria, though no formal indication exists yet due to lack of evidence on optimal dose and regimen. The proposed Phase II clinical trial will define dosing and administration strategies for FMT in recurrent UTIs. If effective, this ecological approach could provide a novel therapeutic alternative to antibiotics for one of the most common infectious diseases worldwide

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Recurrent Urinary Tract Infections in Women

Interventions

Freeze-dried product made of fresh fecesBIOLOGICAL

FMT represents an ecological alternative for restoring the damaged intestinal ecosystem in this infection, increasing ecological diversity and thus limiting the spread of the pathogen. Recurrence of C. difficile is its only approved indication. The impact of FMT on the intestinal ecosystem is attributable to intraspecific bacterial competition: commensal microorganisms (sensitive and non-virulent) have more effective growth rates than pathogenic bacteria (resistant and virulent), so FMT produces an ecological replacement in favor of grafting the donor microbiota and eliminating antibiotic-resistant clones.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: Women ≥18 years of age with UTIs (≥3 episodes in one year or ≥2 in six months) who meet at least one of the following criteria * UTIs despite having used other prophylactic strategies. * HUTI due to resistant bacteria (ESBL- or carbapenemase-producing Enterobacteriaceae, and quinolone-resistant Pseudomonas aeruginosa or Enterococcus faecium). * Allergy or previous adverse reactions to available oral antibiotics (usually beta-lactams, but could occur with other antibiotic families) for prophylaxis and/or treatment. Exclusion Criteria: * Have symptoms compatible with symptomatic UTI at the time of inclusion or be undergoing treatment for it. * Be receiving another preventive strategy for UTIs at the time of study inclusion: prophylactic antibiotics, bladder instillation with hyaluronic acid, D-mannose, or therapeutic vaccines. In the case of the latter, Version 3.0\_ March 22, 2023 13 patients who have received them must have had at least two recurrences despite their administration. * Rifaximin allergy. * Inability to understand the study and sign the informed consent form, and to collect stool and urine samples. * Pregnancy or breastfeeding * Patients with bone marrow or solid organ transplants (patients who have been transplanted for ≥ 5 years and are stable from a transplant perspective are allowed to be included). * Any clinically significant disease at the investigator's discretion, other than UTIs, that is not medically controlled at the time of study inclusion. * Patients with lithiasis or permanent catheters (patients with self-catheters are excluded).

Locations (1)

IRyCIS - FIBIO Hospital Ramón y Cajal

Madrid, Madrid, Spain

Outcomes

Primary Outcomes

Assess the usefulness of TMF in preventing episodes of ITUr.

Proportion (%) of patients free of ITUr 12 months after the start of the study.

Time frame: 12 months

Secondary Outcomes

To evaluate the efficacy of two different TMF dosages in modifying the microbiota and achieving a reduction in the frequency of episodes in patients with rUTI.

Proportion of patients recurrence-free at 12 months (%)

Time frame: 12 months

To evaluate the efficacy of two different TMF dosages in modifying the microbiota and achieving a reduction in the frequency of episodes in patients with rUTI.

Recurrence-free time (days)

Time frame: 12 months

To evaluate the efficacy of two different TMF dosages in modifying the microbiota and achieving a reduction in the frequency of episodes in patients with rUTI.

Time between recurrences (days)

Time frame: 12 months

To evaluate the efficacy of two different TMF dosages in modifying the microbiota and achieving a reduction in the frequency of episodes in patients with rUTI.

Annual recurrence rate (number of recurrences per patient per year, additional clinical information such as whether the symptoms are more like cystitis or pyelonephritis, and the need for hospital admission).

Time frame: 12 months

Tolerability and safety of FMT

Proportion of the following adverse reactions: diarrhoea, abdominal pain, nausea, fever, low-grade fever, abdominal distension, vomiting, constipation, flatulence, rectal bleeding, skin rash, others).

Time frame: 12 months

Data from ClinicalTrials.gov

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