Efficacy of Urinary Microbiota Transplantation (UMT) in Cystitis Glandularis (CG) Patients With Pelvic Lipomatosis (PL)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Symptom Response Assessed by ≥50% Reduction in Interstitial Cystitis Symptom Index (ICSI) Score
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
UMT
Participants in this arm will receive intravesical instillation of urinary microbiota transplantation (UMT) once weekly for 4 consecutive weeks. The UMT product is prepared from donor urine via differential centrifugation, sterile filtration, and reconstitution in sterile PBS, supplemented with myriocin and metabolite-rich supernatant, and confirmed sterile prior to administration.
干预措施: Urinary Microbiota Transplantation (UMT) (Biological)
Control
Participants in this arm will receive intravesical instillation of sterile normal saline (placebo) once weekly for 4 consecutive weeks, following the same administration schedule and procedure as the experimental UMT arm. The placebo is identical in appearance and administration method to the UMT product to maintain the double-blind design.
干预措施: 0.9% Sodium Chloride Injection (Normal Saline, Placebo) (Drug)
结局指标
主要结局
Symptom Response Assessed by ≥50% Reduction in Interstitial Cystitis Symptom Index (ICSI) Score
时间窗: Week 12 (12 weeks after the first intravesical instillation)
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.
次要结局
未报告次要终点