Probiotics as a Prophylactic Aid in Women With Recurrent Urinary Tract Infections (UTI's)

Study Overview
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Brief Summary
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To investigate if administration of probiotics, either orally or vaginally, Can reduce the number of episodes of acute bacterial cystitis and/or Has tolerable adverse effect profile Improves general QoL in these women Improves the immune function and other physiological stress markers Reduces inflammation in urinary bladder epithelium

Detailed Description
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Chronic recurrent bacterial cystitis is a condition that is disabling to a great extent and which influences quality of life and freedom of movement. The episodes can be painful, and lead to extensive use of antibiotics, which in itself promotes development of bacterial strains increasingly resistant to antibiotics, but do not prevent relapses. Almost all cystitis' in women are ascending infections from bacteria in the vagina, following colonization from the rectum. There have, however, been reported indications that there may be bacteria colonies within the urothelium that might give rise to relapses of the infections, rather than pure reinfection from ascending pathogens. Probiotics are cultures of viable microorganisms, which show a positive effect on the general condition of the host when administered. Among the lactic acid bacteria (LAB), lactobacilli are the most commonly used for probiotics, and they have an excellent safety record. In terms of UTI, weekly or twice weekly intravaginal instillation of Lactobacillus strains GR-1 and B-54 have led to reduced recurrences. This concept has been supported by a 2006 pilot study showing that intravaginal administration of Lactobacillus crispatus GAI 98322 every two days for one year, had the potential to reduce the UTI recurrences. Another approach has been taken whereby lactobacilli are administered orally with a view of simulating how the pathogens reach the vagina. The studies have shown that L. rhamnosus GR-1 and L. reuteri (formerly fermentum) RC-14 can reach the vagina after daily oral ingestion, and they can lower the bacterial and yeast pathogen numbers. The aim of the study is to try to normalize the vaginal bacteriological milieu so that the more pathogenic subpopulation of bacteria strains are displaced and are less likely to cause UTI.

Official Title
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Probiotics/Lactobacillus as a Prophylactic Aid in Recurrent Bacterial Cystitis in Women. A Randomized, Prospective, Double-Blinded, Placebo Controlled, Multi-Center Study.

Conditions
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Urinary Tract Infections

Intervention / Treatment
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* Dietary Supplement: UREX-cap-5
* Dietary Supplement: UREX-cap-5
* Dietary Supplement: Placebo Y cap G-3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women 18-70 years old spontaneous urination > 3 UTI's previous year no ongoing prophylactic antibiotic treatment Exclusion Criteria: > 50 ml residual urine neurological bladder disease known neoplasia, kidney stone or urinary tract abnormalities use og indwelling catheter pregnancy diabetes infrequent voiding pattern symptoms that indicate interstitial cystitis creatinin > 250 micmol/L participating in other clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Probiotic vaginal capsules<br>Probiotic vaginal capsule, placebo oral capsule | Dietary Supplement: UREX-cap-5<br>* Size 3, white/white capsule, each containing 180 mg of a standardized, light beige fine powder consisting of freeze-dried cultures of: Lactobacillus rhamnosus, GR-1® (50%) Lactobacillus reuteri, RC-14® (50%) Ingredients Powder: Cultures, glucose anhydrate, potato starch, microcrystalline cellulose and magnesium stearate. Capsule: Gelatine, titanium dioxide Concentration Minimum of 5.4 billion (5.4 x 109) Colony Forming Units per capsule by end of bulk shelf life. Application For use as a dietary supplement. Packaging 20,000 capsules packaged in heat-sealed foil pouch.<br>|
| Placebo Comparator: placebo<br>placebo oral capsule, placebo vaginal capsule | Dietary Supplement: Placebo Y cap G-3<br>* Size 3, white/white capsule, each contaiing180 mg placebo blended powder. Daily oral and vaginal intake for a total duration of 6 months<br>|
| Active Comparator: Probiotic oral capsules<br>Probiotic oral capsules, placebo vaginal capsules | Dietary Supplement: UREX-cap-5<br>* Size 3, white/white capsule, each containing 180 mg of a standardized, light beige fine powder consisting of freeze-dried cultures of: Lactobacillus rhamnosus, GR-1® (50%) Lactobacillus reuteri, RC-14® (50%) Ingredients Powder: Cultures, glucose anhydrate, potato starch, microcrystalline cellulose and magnesium stearate. Capsule: Gelatine, titanium dioxide Concentration Minimum of 5.4 billion (5.4 x 109) Colony Forming Units per capsule by end of bulk shelf life. Application For use as a dietary supplement. Packaging 20,000 capsules packaged in heat-sealed foil pouch.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in number og episodes og lower UTI |  | 6 months intervention period | 
| Improvement of QOL |  | 6 months intervention period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of immune function |  | 6 months | 
| Effects are non-dependant og nutritional status |  | 6 month2 | 
| Effects are non-dependant of known factors contributing til UTI's |  | 6 months | 
| Decreases inflammation in the urinary bladder epithelium |  | 6 months | 
| Normalizes vaginal microflora |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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probiotics, QoL, inflammation, nutritional factors, prophylactic aid, Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC-14, Recurrent lower UTI in women