Clinical Trial of L. Reuteri in Urinary Tract Infections in Non Pregnant Women

Study Overview
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Brief Summary
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RCT to evaluate the safety and efficacy of Lactobacillus reuteri DSM 16666 & Lactobacillus reuteri DSM 17938 to significantly modify the frequency of clinical or bacteriological cure in women with non complicated acute cystitis who receive probiotics for 12 days compared with the frequency in women who receive placebo.

Detailed Description
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Randomized, double blind, placebo controlled, pilot trial to evaluate the safety and efficacy of L. reuteri in non menopausal women with non complicated cystitis in terms of the frequency of clinical or bacteriological cure. Secondary outcomes will be a) time to clinical/laboratory relapse in at least 70% of women with non complicated acute cystitis who receive probiotics for 12 days compared with the time in women who receive placebo; b) frequency of clinical/laboratory and bacteriologic relapse in women with non complicated acute cystitis who receive probiotics for 12 days compared with the frequency in women who receive placebo, at day 30 after treatment start and c) frequency of adverse related events in women with non complicated acute cystitis who receive probiotics for 12 days compared with the frequency in women who receive placebo. In the active product we will use 5*10^8 CFU of Lactobacillus reuteri DSM 16666 & Lactobacillus reuteri DSM 17938 + cranberry extract. The control group will recibe Cranberry extract. The products will be taken twice per day, morning and evening.

Official Title
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Safety, and Effectiveness of Lactobacillus Reuteri for the Treatment of Urinary Tract Infections in Women: A Pilot Randomized Clinical Trial (RCT)

Conditions
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Urinary Tract Infections

Intervention / Treatment
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* Combination Product: Lactobacillus reuteri
* Dietary Supplement: Sachet with cranberry + placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non pregnant pre menopausal women Minimum age 18 years Uncomplicated cystitis diagnosed by urine dipstick testing (nitrates +, leukocytes esterase and/or 105 CFU/ml or nitrates +, leukocytes esterase + and/or 102 -103 CFU/ml+ clinical symptoms) and an evaluation of the presence of typical related symptoms. In particular, frequency (frequent voiding of urine), urgency (the urge to void immediately), dysuria (painful voiding), and/or suprapubic pain. Verbal and Written Informed Consent for participation in the study Exclusion Criteria: Acute cystitis symptoms for >1week before the first visit Diabetes mellitus, Congenital urinary tract abnormality Lactating women Female who intend to become pregnant during the study or within 3 months after the completion of the study Vaginal discharge + fever (>37.5oC) Diagnostic of sexually transmitted diseases Use of an indwelling catheter or an intermittent self-catheterisation program Presence of neurogenic bladder, or Use of any antibiotic 2 weeks before Day 1 in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial, double blind allocation concealment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lactobacillus reuteri<br>Women in experimental branch will receive two sachets. Sachet one contains a total of 5*10^8 CFU of Lactobacillus reuteri DSM 16666 & Lactobacillus reuteri DSM 17938, mixed with maltodextrin for flowability during production. Sachet two contains instant cranberry drink composed of Cranberry extract, xylitol, cranberry aroma, monosodium citrate, zink gluconate, silica. | Combination Product: Lactobacillus reuteri<br>* Sachet one contains a total of 5*10^8 CFU of Lactobacillus reuteri DSM 16666 & Lactobacillus reuteri DSM 17938, mixed with maltodextrin for flowability during production. Sachet two contains instant cranberry drink composed of Cranberry extract, xylitol, cranberry aroma, monosodium citrate, zink gluconate, silica. The products will be taken twice per day, morning and evening. The daily dose in the active group will be at least 5*10^8 CFU of L.reuteri DSM16666 and L. reuteri DSM17938), PAC-A and zinc<br>|
| Placebo Comparator: Sachet with cranberry + placebo<br>Women in control branch will receive two sachets. Sachet one contains only Maltodextrin and sachet two contains instant cranberry drinkcomposed of Cranberry extract, xylitol, cranberry aroma, monosodium citrate, zink gluconate, silica Both sachets should be emptied in a glass and mixed with 200 ml of cold water | Dietary Supplement: Sachet with cranberry + placebo<br>* Sachet one contains placebo for probiotics (maltodextrin). Sachet two contains instant cranberry drink composed of Cranberry extract, xylitol, cranberry aroma, monosodium citrate, zink gluconate, silica.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical and bacteriological cure | Frequency of clinical or bacteriological cure in women with non complicated acute cystitis who receive probiotics for 12 days compared with the frequency in women who receive placebo | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical or bacteriological relapse | Time to clinical/laboratory relapse in at least 70% of women with non complicated acute cystitis who receive probiotics for 12 days compared with the time in women who receive placebo | 30 days | 
| Adverse events | • Frequency of adverse related events in women with non complicated acute cystitis who receive probiotics for 12 days compared with the frequency in women who receive placebo | 14 days |