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

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

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

Study Overview

• Status: Unknown
• Conditions: Urinary Tract Infections
• Intervention / Treatment: Dietary supplement: UREX-cap-5; Dietary supplement: Placebo Y cap G-3

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Trondheim, Norway, 7006
    • Active, not recruiting
    • St.Olavs Hospital
  • Akershus
    • Lørenskog, Akershus, Norway, 1478
      • Recruiting
      • Akershus Universitetssykehus HF
      • Contact: Caroline U Skagemo, MD; Phone Number: +47 02900111; Email: cask@ahus.no
      • Contact: Gunn Iren Meling, PhD, MD; Phone Number: +47 02900 111; Email: gmel@ahus.no
      • Principal Investigator: Caroline U Skagemo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Probiotic vaginal capsules; Probiotic vaginal capsule, placebo oral capsule	Dietary supplement: UREX-cap-5; 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.
Placebo Comparator: placebo; placebo oral capsule, placebo vaginal capsule	Dietary supplement: Placebo Y cap G-3; Size 3, white/white capsule, each contaiing180 mg placebo blended powder. Daily oral and vaginal intake for a total duration of 6 months
Active Comparator: Probiotic oral capsules; Probiotic oral capsules, placebo vaginal capsules	Dietary supplement: UREX-cap-5; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University Hospital, Akershus
• Collaborators: University of Oslo; Karolinska Institutet; St. Olavs Hospital; Folkehelsa
• Investigators: Principal Investigator: Caroline U Skagemo, MD, Akershus Universitetssykehus HF; Study Director: Gunn Iren Meling, PhD. MD, Akershus Universitetssykehus HF

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Anticipated): December 1, 2009
• Study Completion (Anticipated): December 1, 2010

Study Registration Dates

• First Submitted: October 28, 2008
• First Submitted That Met QC Criteria: October 28, 2008
• First Posted (Estimate): October 29, 2008

Study Record Updates

• Last Update Posted (Estimate): October 31, 2008
• Last Update Submitted That Met QC Criteria: October 29, 2008
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: QoL; probiotics; inflammation; nutritional factors; prophylactic aid; Lactobacillus rhamnosus GR-1; Lactobacillus reuteri RC-14; Recurrent lower UTI in women
• Additional Relevant MeSH Terms: Urologic Diseases; Infections; Urinary Tract Infections; Anti-Infective Agents; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Renal Agents; Methenamine; Methenamine hippurate; Methenamine mandelate
• Other Study ID Numbers: S-08458d (REK); 08/7922(Shdir)