Study name |
A randomized, placebo‐controlled, pilot study to evaluate the effects Winclove CLEAR in female recurrent urinary tract infection patients (PROTON) |
Methods |
Study design
Study dates
Study duration and follow‐up
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Participants |
General information
Country: The Netherlands
Setting: single centre
Inclusion criteria: recurrent UTI for at least 2 years (defined as 3 or more episodes of UTI/year); at least 3 UTIs in the preceding 12 months; 18 and 70 years; willing to take probiotics and refrain from UTI prophylaxis during the study; signed informed consent
Exclusion criteria: current (complicated) suspected UTI or cystitis; prophylactic antibiotic usage during the intervention period; probiotic, D‐mannose or cranberry extract usage during the intervention period; use of UTI prophylactics/treatments during the intervention period, other than mentioned under point 2 & 3, which in the opinion of the investigator may significantly interfere with the evaluation of the study objectives, including oestrogen treatment; concurrently enrolled in another intervention study (observational studies or inclusion following completion of another study is allowed (4‐week wash‐out)); known to have interstitial cystitis or bladder pain syndrome; known to have a complex bladder disturbance (e.g. cystoplasty, renal and bladder calculus, significant hydronephrosis or current pyelonephritis); known to have severe renal or hepatic failure; known to be severely or terminally ill; known to have non‐resolvable urinary obstruction; known to have a history of adverse drug reaction to yoghurt or milk products or a demonstrated intolerance to the probiotics used lactose intolerance is NOT an exclusion criterion; known to be intolerant or allergic to any of the ingredients in both Winclove CLEAR and matched placebo; spinal cord injury with suprapubic permanent catheter; requiring full (invasive) mechanical ventilation; receiving immunosuppressant medications or having an underlying immunosuppressive disease (e.g. HIV, end‐stage/progressive DM, multiple sclerosis or cerebrovascular disease); planned oral/vaginal/urinary tract/bladder/gastrointestinal surgery during the intervention period; recent oral/vaginal/urinary tract/bladder surgery/gastrointestinal (within last 3 months); pregnant (screened with a positive pregnancy test), lactating or intending to become pregnant during the study; women of childbearing potential need to use contraceptives; use of intravaginal products (e.g. spermicides) except for menstrual products; any other condition, which, in the opinion of the investigator, may significantly interfere with the evaluation of the study objectives
Target sample size: 40
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Interventions |
Treatment group (40 participants)
Consume a daily dose of 4 g of Winclove CLEAR containing 4E+09 CFU of live probiotic strains L. pentosus W2 (KCA1), L. acidophilus W22, L. plantarum W21, L. salivarius W24, L. brevis W63, L. casei W56 and L. helveticus W74, cranberry extract (36 mg PACs) and D‐mannose (1 g) for a period of 6 consecutive months.
Control group (20 participants)
Placebo: consume a daily dose of 4 g of the placebo formulation, similar in taste/smell/appearance but without active ingredients (e.g. probiotic, cranberry, D‐mannose), for a period of 6 consecutive months
Co‐interventions or additional treatments
Follow‐up details
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Outcomes |
Primary outcomes
The differences in QoL between treatment arms according to UTI‐QoL‐questionnaire data and SF‐36 scores after the intervention period
The difference in UTI incidence between treatment arms, as measured by the mean number of patient‐reported UTI episodes during the intervention period
The difference in UTI symptom severity between treatment arms, as measured by mean Symptom & Burden questionnaire scores during the intervention period
Secondary outcomes
The difference in UTI incidence between treatment arms, as confirmed by a microbiome analysis of urine samples during the intervention period (ratio of lactobacilli to common uropathogens)
The difference between treatment arms in UTI‐related healthcare expenditures during the intervention period, as determined by the Health Economics questionnaire at day 180
The total number of subjects in the active treatment arm, and the difference in the number of subjects between treatment arms, where probiotic strains from the formulation are identified in urine samples at days 1, 60, 120 and 180 as determined by a primary species‐specific 16S ribosomal RNA sequencing analysis and – if positive – a follow‐up strain‐specific real‐time quantitative 16S ribosomal RNA gene polymerase chain reactions
The difference in UTI duration between treatment arms, as determined by mean patient‐reported UTI duration during the intervention period
Time points
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Starting date |
January 2019 |
Contact information |
Dr J. Flach Email: Joost.flach@cr2o.nl Phone: +31 6 40275130 |
Notes |
Funding: This study is performed at the research facility of CR2O by Prof. Dr. Eric Claassen (Principal Investigator) and Drs. Joost Flach (Coordinating Investigator). |