Recurrent Urinary Tract Infections in Women
Conditions
Keywords
Women, Urinary tract infections, Fecal microbiota
Brief summary
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
Detailed description
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
Interventions
BIOLOGICALFreeze-dried product made of fresh feces
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.
Sponsors
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess the usefulness of TMF in preventing episodes of ITUr. | 12 months | Proportion (%) of patients free of ITUr 12 months after the start of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 12 months | Proportion of patients recurrence-free at 12 months (%) |
| Tolerability and safety of FMT | 12 months | Proportion of the following adverse reactions: diarrhoea, abdominal pain, nausea, fever, low-grade fever, abdominal distension, vomiting, constipation, flatulence, rectal bleeding, skin rash, others). |
| FMT impact on intestinal bacterial ecosystem | 12 months | Document clonal replacement in classical cultivable bacteria and demonstrate the impact of FMT on the entire intestinal bacterial ecosystem through next-generation sequencing of the 16S rDNA gene and metabolic monitoring by determining short-chain fatty acids. |
Countries
Spain
Contacts
PRINCIPAL_INVESTIGATORAlex Soriano, MD
HOSPITAL CLINIC DE BARCELONA, SPAIN
PRINCIPAL_INVESTIGATORAntonio Ramos, MD
HOSPITAL UNIVERSITARIO PUERTA DE HIERRO, MADRID, SPAIN
PRINCIPAL_INVESTIGATORLuis Llanes, MD
HOSPITAL UNIVERSITARIO DE GETAFE, MADRID, SPAIN
Outcome results
None listed