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

Official title

A Randomized Controlled Trial of D-mannose for the Prophylaxis of Recurrent Urinary Tract Infections in Post-menopausal Women

Overview

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.

Interventions

• Dietary supplement D-Mannose
  D-mannose (2g, i.e., 4 x 500mg capsules) daily for 12 months.
• Dietary supplement Placebo
  Placebo daily for 12 months.

Primary outcome measures

• Failure rate [Time frame: Through study completion, an average of 5 years]

Secondary outcome measures (3)

• Number of UTI antibiotic treatments [Time frame: Through study completion, an average of 5 years]
• Symptom severity [Time frame: Through study completion, an average of 5 years]
• Serious adverse events associated with D-mannose [Time frame: Through study completion, an average of 5 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

United States · 1 center

• University of Texas Southwestern Medical Center — Dallas

Identifiers

NCT: NCT06940622 · STU-2024-1090

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗