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.
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.
Eligibility
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