Probiotics to reduce the incidence of recurrent urinary tract infections

Completed

Conditions: Personal history of diseases of genitourinary system,

Registration Number: CTRI/2014/02/004425

Lead Sponsor: Indian Council of Medical Research

Brief Summary: | |

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|Recurrent Urinary tract infection (UTI) continues to be a major health problem in women and is now complicated by increasing cases of antibiotic resistance. In females, urinary pathogens almost always infect the host by ascending from the rectum or vagina to the urethra and bladder (Lane MC et al, *Infect Immun* 2005; 73: 7644-7656). Likewise, the probiotic bacteria that predominate in the vagina of healthy women, spread to the rectum and perineum and form a barrier to prevent entry by uropathogens (Reid G & Bruce AW, *World J Urol* 2006; 24: 28-32). Inverse association has been reported between H2O2 producing lactobacilli and vaginal *E. coli* colonization in women with recurrent UTIs (Gupta K et al, *J Infect Dis* 1998; 178: 446-450). In a similar manner, Lactobacilli colonizing the intestine via oral route emerge at the rectum and transfer passively to the vagina and bladder.

Because of increasing cases of antibiotic resistance, there is a strong need for preventive measures to control recurrence of the disease. Probiotics are natural products that have been shown to prevent UTI without the use of antibiotics. Probiotic lactobacilli may avert or stop the ascension of uropathogens into the bladder through various mechanisms, including interference with pathogen adhesion, biofilm formation, invasion and growth, expression of virulence factors, and modulation of the hostâ€™s defenses to better fight infection. If it proves to be efficacious, it could subsequently decrease the morbidity and health care costs associated with UTI as well as decrease overall antibiotic use and the corresponding prevalence of antibiotic resistance among UTI causing bacteria.

In two pilot studies, the safety and potential of oral and vaginal probiotics for prevention of recurrent UTI was confirmed (Czaja CA et al, *Infect Dis Obst Gynecol* 2007: 1-8; Anukam KC et al, *Adv Urol* 2009: 1-5). In a Phase II trial using vaginal probiotic, high colonization with vaginal lactobacilli was associated with a reduction in recurrence of UTI (Stapleton AE et al, *Clin Infect Dis* 2011; 52:1212-1217). Considering the possible role, that probiotics may modulate the urinary microflora, this randomized double blind placebo controlled study is designed **to determine the effect of administering oral or/and vaginal probiotic on the microflora in females with history of recurrent UTI. Another objective is to evaluate the reduction in incidence of a/symptomatic UTI compared to placebo.**

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|Bacterial vaginosis (BV) is a condition characterized with complex multi-species microbiota dominated with

*Gardnerella vaginalis* and other bacterial pathogens replacing probiotic lactobacilli. BV is also a risk factor for recurrent UTI. In a study by Onderdonk AB, VSL#3 suppressed the growth of a common vaginal pathogen *Gardnerella vaginalis* in continuous culture simulating the vaginal environment (*J Clin Gastroenterol* 2006; 40:256-259). VSL#3 strains were found to colonize in the intestine thereby increasing fecal concentration of *Streptococcus thermophilus*, bifidobacteria and lactobacilli (Venturi et al, Aliment Pharmacol Ther 1999; 13: 1103-1108). The probiotic strains in VSL#3 were detected in human feces after oral bacteriotherapy (Brigidi et al, *Int J Food Microbiol* 2003; 81: 203-209). Considering this, we hypothesize that VSL#3 given orally may prevent ascension of pathogens from rectum to urinary bladder.Florisia has been proven effective in curing bacterial vaginosis in a few clinical trials. In an Indian study, Florisia cured BV in 80% of women and significantly reduced vaginal pro-inflammatory cytokines IL-1Î² and IL-6 (Hemalatha et al,

*Eur J Clin Microbiol Infect Dis*, Epub 10 Jul 2012). In another study, Florisia cured BV in all the enrolled women. Two weeks after completion of therapy, the treatment was successful in 61% of women and vaginal malodor was significantly reduced (Mastromarino et al, *Clin Microbiol Infect* 2009; 15: 67-74).After reviewing the available literature, the study drugs I intend to use in this trial project are VSL#3 oral capsule and Florisia vaginal tablet. Both the products are available in India and will be procured directly either from the market or the manufacturer for the study purposes. VSL#3 is a mixture of 8 different strains of freeze-dried lactic acid bacteria and bifidobacteria; each capsule containing not less than 112.5 billion colony forming units (CFU). Two capsules of VSL#3 will be given once daily for 4 months. Florisia is a vaginal tablet containing at least 1 billion CFU of lyophilized

*L. brevis* CD2, *L. salivarius* subsp. *salicinius*, and *L. plantarum*. One tablet will be inserted in vagina for 8 days every month for 4 months.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Female

Target Recruitment: 176

Inclusion Criteria

Pre-menopausal women aged 18-45 years 2.
History of three or more uncomplicated UTIs diagnosed in the past year, or two uncomplicated UTIs diagnosed in the past six months 3.
Sterile urine culture at baseline 4.
Agree for completion of screening procedures and agree to return for the subsequent follow up visits 5.
Willing to insert vaginal tablet without an applicator 6.
Capable of providing informed consent 7.
Agree to abstain from self-medication with antibiotics for the UTI symptoms 8.
Agree to abstain from antibiotic prophylaxis for recurrent UTI 9.
Agree to abstain from the use of any other intra-vaginal product 10.
Agree to abstain from sexual intercourse during 8 days course of vaginal tablet.

Exclusion Criteria

All pregnant and lactating females 2.
Those suffering from any disease of upper or lower urinary tract including pyelonephritis and UTI due to drug resistant strain 3.
Patient with history of relapse of UTI within 2 wks, prior to starting the enrollment 4.
Symptomatic bacterial vaginosis 5.
Patients with immune-compromised status due to diseases like Diabetes/ AIDS.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine the effect of administering VSL#3 & Florisia (oral & vaginal probiotic) and placebo on the microflora in females with recurrent UTI.	1 year

Secondary Outcome Measures

Name	Time	Method
To evaluate the reduction in the incidence of symptomatic and probable UTI compared to placebo.	1 year

Trial Locations

Locations (1): Department of Microbiology
🇮🇳
Chandigarh, CHANDIGARH, India
Department of Microbiology
🇮🇳Chandigarh, CHANDIGARH, India
Dr Varsha Gupta
Principal investigator
919646121571
varshagupta_99@yahoo.com