Purpose: This is a pilot randomized double-blind placebo controlled trial of anticholinergic or beta-3 agonist medication with or without concomitant probiotic therapy in women initiating medication therapy for overactive bladder (OAB). The aims of this study are to:

1. Explore how concomitant probiotic therapy influences response to medication for OAB in a randomized controlled trial
2. Investigate whether 4 weeks of probiotic therapy alters the urinary microbiome
3. Assess for predictors of response to therapy

Participants: Women 18 years of age or older presenting to the Division of Urogynecology and Reconstructive Pelvic Surgery clinic with OAB/UUI or UUI-predominant mixed incontinence who desire nonsurgical therapy will be eligible for participation.

Procedures (methods): The study will be conducted over a two-year time frame and the primary outcome will be subjective improvement in symptoms as assessed by the Patient Global Impression of Improvement (PGI-I) validated questionnaire at 4 weeks after initiating anticholinergic or beta-3 agonist medication and study drug. The study aims to recruit up to 140 participants randomized in a 1:1 ratio to either concomitant probiotic or placebo medication.

Overactive bladder (OAB) is a highly prevalent condition that negatively impacts the lives of millions of adults in the United States. Anticholinergic and beta-3 agonist medications are commonly used to treat OAB but compliance is low due to variable efficacy and bothersome side effects. The existence of a urinary microbiome was recently discovered and early investigations have revealed that lower Lactobacillus load is correlated with the presence of OAB symptoms and a poorer response to anticholinergic therapy.

This proposed pilot study is a randomized double-blind placebo-controlled trial (RCT) of concomitant probiotic therapy in women initiating medication therapy for OAB to explore how probiotics influence response to anticholinergic and beta-3 agonist medications, investigate whether probiotic therapy alters the urinary microbiome, and assess for predictors of response to therapy.

Primary Aim: To explore how concomitant probiotic therapy influences response to medication for OAB in a RCT

Secondary Aims:

1. To investigate whether 4 weeks of probiotic therapy alters the urinary microbiome.
2. To assess for predictors of response to therapy

Inclusion Criteria:

• Women age ≥ 18 years
• English-speaking
• OAB/UUI or urge-predominant mixed incontinence per the Medical Epidemiologic and Social Aspects of Aging (MESA) questionnaire

Exclusion Criteria:

• Neurogenic bladder or urinary retention (postvoid residual (PVR) >150 mL)
• Probiotic use within the past 4 weeks
• Inflammatory bowel disease or history of bariatric surgery
• Pelvic organ prolapse past the hymen
• Current symptomatic UTI or systemic antibiotic exposure within 4 weeks
• Current treatment for recurrent UTI or history of recurrent UTI in the last 6 months
• Immunosuppressive therapy (i.e., prednisone or chemotherapy)
• Contraindication to anticholinergic or beta-3 agonist medication (including pregnancy)
• Prior neuromodulation therapy for OAB
• Inability or unwillingness to comply with study protocol

Deidentified individual data that supports the results will be shared until 24 months following publication of the first manuscript from this study provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

Until 24 months following publication of the first manuscript from this study.

The investigator who proposes to use the data has to have approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

Probiotic study drug and identical appearing placebo tablet