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A Trial of D-mannose for the Prophylaxis of Recurrent Urinary Tract Infections

Not Applicable
Not yet recruiting
Conditions
Recurrent UTIs
Recurrent Urinary Tract Infections
Recurrent Urinary Tract Infections in Women
Recurrent Urinary Tract Infection
Cystitis Recurrent
Cystitis Chronic
UTI
UTI - Urinary Tract Infection
UTI - Lower Urinary Tract Infection
Registration Number
NCT06940622
Lead Sponsor
University of Texas Southwestern Medical Center
Brief Summary

A randomized, double-blind, placebo-controlled, 12-month study to determine the effectiveness of D-mannose (2g daily) supplementation in rUTI (recurrent urinary tract infection) prevention in post-menopausal women.

Detailed Description

The proposed study on D-mannose prophylaxis is designed to address a critical unmet medical need to improve the understanding and prevention of rUTI (recurrent urinary tract infection) in post-menopausal women, a population disproportionately affected by rUTI and understudied. The efficacy of D-mannose on preventing uncomplicated rUTI will be elucidated, and additional study measures (including urine culture and one-hour D-mannose test results) may help establish an ideal candidate for responding to daily D-mannose intake over time. The proposed study will follow CONSORT guidelines for randomized clinical trial studies.

Aim 1. Test the hypothesis that D-mannose provides effective rUTI prophylaxis in post-menopausal women over 6 months.

Aim 2. Test the hypothesis that D-mannose provides effective rUTI prophylaxis in post-menopausal women beyond 6 months and up to one year.

The overarching hypotheses are that (1) D-mannose will be found superior to placebo in preventing rUTI in post-menopausal women over 6 months as suggested by one prior RCT7 (Aim 1) and (2) D-mannose will remain effective for rUTI prophylaxis up to one year (Aim 2).

Ninety (90) women currently UTI-free and with a history of uncomplicated rUTI, defined as ≥ 2 symptomatic UTIs in 6 months or ≥ 3 symptomatic UTIs in 12 months, will be enrolled and randomized (2:1 ratio) to receive D-mannose (2g, i.e., 4 x 500mg capsules) or placebo daily for 12 months.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
Female
Target Recruitment
90
Inclusion Criteria
  • Female, post-menopausal, age ≥ 55 years old
  • Diagnosis of recurrent UTI, defined as ≥ 3 symptomatic culture-proven UTI episodes in 12 months or ≥ 2 in 6 months.
  • Currently free from a UTI determined based on absence of symptoms as determined by the UTI symptom assessment questionnaire79 and negative urine culture (<103 colony forming units per ml of urine).
  • Able to attend all follow-up appointments for the study.
  • A negative upper and lower urinary tract evaluation, including pelvic examination for pelvic organ prolapse (less than stage 2), measurement of post-void residual (less than 50 ml), and imaging (renal ultrasound and standing voiding cystourethrogram) to exclude kidney stone, hydronephrosis, reflux, or urethral diverticulum.
Exclusion Criteria
  • Current use of D-mannose. Patients willing to stop taking D-mannose will be offered to join the trial after a 4-week wash-out period.
  • Complicated UTIs, including need for catheter drainage or intermittent catheterization, neurogenic bladder, bladder augmentation, or urinary diversion.
  • Ongoing supplement use (Box 1). Patients willing to stop taking the listed supplements will be offered to join the trial after a 4-week wash-out period.
  • Evidence of upper tract infection (pyelonephritis), including temperature higher than 38°C, flank/lumbar pain or tenderness
  • Diagnosis of interstitial cystitis or overactive bladder syndrome
  • Prophylactic antibiotics started in the last 3 months and unwilling to discontinue, or intention to start in the next 12 months
  • Use of Uromune or other vaccine approaches to reduce rUTI
  • Participation in a research study involving an investigational product in the past 12 weeks
  • Receipt of phage treatment
  • History of chronic diarrhea requiring regular therapy
  • Inability to swallow or known history of gastrointestinal malabsorption
  • History of recurrent vaginal yeast infections
  • Systemic disease precluding enrollment in this study (uncontrolled diabetes with HgA1C above 7, ongoing chemotherapy or immunotherapy, renal insufficiency [creatinine > 1.5 g/dl]), mental or cognitive impairment, weight loss diet requiring excessively large amounts of fluid intake, or other health-related specific diet).
  • Nursing home resident
  • BMI >40

Box 1 Supplements to avoid

  • Multi-Vitamins and Multi-Mineral capsules
  • Specific Vitamins or Minerals (e.g., Calcium, Citrical, Calcium Gummies, Vitamin A, D, Niacin, Pyridoxine, Selenium, Vitamin E, B6, Iron, Omega 3, D3, Magnesium, B-Complex, Women's Ultra MultiVitamin, GNC B-Complex, B-12, PreserVision Areds2, Vitamins D, B Pollen)
  • Probiotics
  • Cranberry Mannose or Cranberry Extract Weight loss products to avoid
  • Medifast
  • Vitafusion
  • OptiVin Products
  • Appetite Suppressants
  • Keto-Fuel

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Failure rateThrough study completion, an average of 5 years

To determine whether prophylaxis with D-mannose reduces the incidence of UTI episodes compared to placebo. "Failure rate," defined as having 2 UTIs in 6 months or 3 in one year.

Secondary Outcome Measures
NameTimeMethod
Symptom severityThrough study completion, an average of 5 years

To investigate if D-mannose reduces the severity of UTI symptoms compared to placebo. Record symptom severity using a validated UTI symptom assessment questionnaire.

Number of UTI antibiotic treatmentsThrough study completion, an average of 5 years

To investigate if D-mannose reduces the need for antibiotic use due to recurrent UTIs (measured as number of antibiotic courses for symptomatic culture-proven UTI episodes) compared to placebo.

Number of UTI antibiotic treatments during the 6 months of treatment. If the participant receives \>1 antibiotic course for UTI without symptom relief, it is regarded as one episode and counted as one antibiotic treatment. If there has been an asymptomatic period of at least 14 days in between two UTI antibiotic courses, this will be regarded as a new antibiotic treatment.

Serious adverse events associated with D-mannoseThrough study completion, an average of 5 years

To determine the frequency of serious adverse events associated with D-mannose. Number of participants who experienced adverse events \>= Grade 3, as defined by Common Terminology Criteria for Adverse Events by CTCA version 5.0.

Trial Locations

Locations (1)

University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

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