a trial of d-mannose for the prophylaxis of recurrent urinary tract infections

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

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.

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 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

Keywords: d-mannose dmannose uti ruti recurrent urinary tract infection urinary tract infection cystitis chronic uti chronic cystitis