Investigation of Brain Mechanisms Involved in Urgency Urinary Incontinence

Phase 4

Recruiting

• Conditions: Urgency Urinary Incontinence
• Interventions: Drug: Trospium; Drug: Placebo oral tablet

• Registration Number: NCT04227184
• Lead Sponsor: Becky Clarkson

Brief Summary

This is a randomized double-blind crossover trial of trospium and placebo in women with urgency urinary incontinence, with evaluation (history, physical, incontinence evaluation and brain MRI) at baseline, and after each course of therapy. The investigators will evaluate functional brain changes in relation to bladder improvement in order to improve our knowledge of the brain's role in the continence mechanism.

Detailed Description

Urgency urinary incontinence (UUI) costs the US $83 billion/year, owing in large part to its increased prevalence with age, particularly in women: 9% of those over age 18 and 36% of those over age 65. UUI also impairs quality of life, social interaction, and independence; contributes to functional decline; and increases risk for falls, hip fractures, UTIs, urosepsis, anxiety, depression, and institutionalization.The cause of UUI is unknown. Its urgency and leakage are usually ascribed to detrusor overactivity (DO, involuntary detrusor contraction), suggesting that the cause is intrinsic to the bladder even though DO is not always confirmed on testing. Because of this assumption, most therapies target the bladder albeit with only moderate success: e.g., anticholinergics reduce incontinence episodes but their benefit and tolerability (especially for older adults) are sufficiently low that 75% of patients discontinue them within a year. By contrast, therapies such as biofeedback-assisted pelvic muscle therapy (BFB) tackle behaviors. Moreover, the use of biofeedback to retrain the brain shows that the central control mechanism can be targeted and improved. Thus, the present proposal is designed to further elucidate this mechanism, thereby paving the way for discovery of new and more effective ways to control UUI. These could transform current treatment and either complement or supplant current therapy.

Study Timeline

• Study First Submitted: 2020-01-09
• Study First Submitted QC: 2020-01-09
• Study First Posted: 2020-01-13
• Study Start: 2020-02-13
• Primary Completion: 2025-02-28
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-02
• Last Update Posted: 2025-04-03
• Study Completion: 2025-10-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 220

Inclusion Criteria

1. 60+ years old
2. Has UUI or urge-predominant mixed incontinence at least 5 times/ week for > 3 months despite treatment for reversible causes

Exclusion Criteria

1. conditions/medications contraindicating trospium
2. If currently taking anticholinergic medications (participant must refrain from anticholinergic medications for 4 weeks prior enrollment in order to be eligible)
3. Impaired mobility or cognition sufficient to preclude following study procedures; MoCA test score <24/30; a clinically-apparent neurological condition
4. Prolapse beyond the hymen
5. Interstitial cystitis
6. Spinal cord injury
7. History of pelvic radiation or advanced uterine/bladder cancer
8. Urethral obstruction (uroflow); PVR >200 ml
9. Medical instability
10. Prior UUI treatment with onabotulinum toxin or neuromodulation
11. Drug interaction or expected medication change during the study
12. Conditions requiring IV antibacterial prophylaxis
13. New incontinence treatment < 3 months prior to enrollment
14. Fecal incontinence, and symptomatic colitis/IBS
15. Contraindications to MRI.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo/Trospium	Trospium	Placebo first for 12 weeks followed by Trospium for 12 weeks.
Trospium/Placebo	Placebo oral tablet	Trospium first for 12 weeks followed by Placebo for 12 weeks
Placebo/Trospium	Placebo oral tablet	Placebo first for 12 weeks followed by Trospium for 12 weeks.
Trospium/Placebo	Trospium	Trospium first for 12 weeks followed by Placebo for 12 weeks

Primary Outcome Measures

Name	Time	Method
Structural brain changes	12 to 24 weeks	Change in grey and white matter volume on MRI compared between responders and non-responders to therapy/placebo. Grey matter and white matter volume of important brain structures will be compared, along with structural integrity of white matter pathways via tractography.
Functional brain changes	12 to 24 weeks	Change in brain functional response to an infusion/withdrawal protocol compared between responders and non-responders to therapy/placebo. Changes are displayed as a map of t-values for each voxel of the brain, showing likelihood of statistical significance of changes.

Trial Locations

Locations (1)

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States