Efficacy of UMT in CG Patients With PL

Peking University First Hospital110 enrolled

Overview

To clinically validate the pathological role of Cer accumulation and evaluate a novel microbiota-targeted intervention, we conducted a comprehensive analysis of bladder mucosal specimens from a well-characterized patient cohort stratified according to the established histopathological criteria for CG severity. Our findings revealed specific accumulation of the sphingolipid species Cer(d18:1/18:0) in high-risk CG tissues, which was absent in both low-risk and control groups. Notably, tissue levels of Cer(d18:1/18:0) demonstrated a strong positive correlation with histopathological grade, highlighting its clinical relevance as a driver of PL-CG progression and supporting its potential utility as a prognostic biomarker. Given the established association between the urinary microbiota and local metabolite production, and considering that the pathogenic urinary microbiota likely serves as the source of this immunomodulatory Cer, we designed and implemented a randomized controlled trial to assess therapeutic remodeling of the bladder microenvironment through UMT. Following the one-month regimen of weekly intravesical instillations, UMT significantly reduced disease burden in PL-CG patients. At the 12-week follow-up, the UMT group exhibited a substantially lower Interstitial Cystitis Symptom Index (ICSI) compared to controls, with an overall response rate of 58.18%. Significant improvements were also observed in key clinical symptoms, including daytime urinary frequency and voiding-related pain. Notably, clinical improvement occurred without a significant reduction in mucosal colonization levels of B. thetaiotaomicron. This observation suggests that UMT's efficacy does not arise from broad bacterial eradication but rather from functional modulation of the microbiota-host interface. Instead, therapeutic benefit was strongly associated with direct depletion of the pathogenic metabolite. Urinary Cer(d18:1/18:0) levels were markedly reduced following UMT, which coincided with the coordinated down-regulation of key pro-inflammatory cytokines in the bladder mucosa, including IL-6, TNF-α, IL-1β, and CXCL1. This sequential cascade thus establishes a clear mechanistic link between pathogenic metabolite clearance, resolution of inflammation, and symptomatic relief.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

Interventions

Urinary Microbiota Transplantation (UMT)BIOLOGICAL

This intervention is a rigorously prepared donor-derived urinary microbiota transplantation product. After passing strict multi-pathogen screening, donor urine is processed via differential centrifugation (3000g for 10min, 10000g for 20min, 100000g for 60min) and sequential sterile filtration through 0.45μm and 0.22μm PES membranes to isolate and purify the microbial fraction. The microbial pellet is resuspended in sterile PBS (autoclaved at 121℃ for 20min), supplemented with 1μM myriocin and metabolite-rich supernatant, and confirmed sterile via final sterility testing before clinical use. Participants receive intravesical instillation once weekly for 4 consecutive weeks for the treatment of high-risk chronic cystitis/interstitial cystitis.

0.9% Sodium Chloride Injection (Normal Saline, Placebo)DRUG

This arm receives intravesical instillation of sterile 0.9% sodium chloride injection (normal saline) as a placebo control. The placebo is identical in appearance, volume, and administration schedule to the urinary microbiota transplantation (UMT) product in the experimental arm, administered once weekly for 4 consecutive weeks to maintain the double-blind study design. The placebo has no therapeutic activity and is used to evaluate the efficacy and safety of UMT for the treatment of high-risk chronic cystitis/interstitial cystitis.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 years at the time of screening * Histologically confirmed high-risk chronic cystitis (pathological grade ≥ 3 or presence of dysplasia) * Elevated urinary ceramide (Cer(d18:1/18:0)) level ≥ 50 ng/mL at baseline * History of failure with standard-of-care therapy for chronic cystitis * Ability to provide written informed consent and comply with study procedures and follow-up * Ability to complete patient-reported outcome questionnaires (e.g., ICSI) independently Exclusion Criteria: * Active urinary tract infection (UTI) or untreated genitourinary tract infection at screening * Severe systemic diseases (e.g., uncontrolled diabetes, malignant tumor, severe cardiovascular/hepatic/renal dysfunction) that may interfere with study evaluation * History of bladder cancer, intravesical chemotherapy or immunotherapy within the past 6 months * Pregnancy or breastfeeding, or planned pregnancy during the study period * Participation in another interventional clinical trial within the past 3 months * Known allergy or hypersensitivity to any component of the UMT product or placebo (normal saline) * Severe mental illness or cognitive impairment that prevents completion of study assessments * Any other condition that, in the investigator's judgment, makes the participant unsuitable for enrollment

Outcomes

Primary Outcomes

Symptom Response Assessed by ≥50% Reduction in Interstitial Cystitis Symptom Index (ICSI) Score

The primary efficacy endpoint is defined as a ≥50% reduction from baseline in the total Interstitial Cystitis Symptom Index (ICSI) score at Week 12 post-treatment initiation. The ICSI is a validated 4-item patient-reported outcome tool that quantifies the severity of interstitial cystitis/bladder pain syndrome symptoms, including urinary frequency, urgency, pain, and nocturia.

Time frame: Week 12 (12 weeks after the first intravesical instillation)