Investigation of Brain Mechanisms Involved in Urgency Urinary Incontinence

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.

Study Overview

• Status: Completed
• Conditions: Urgency Urinary Incontinence
• Intervention / Treatment: Drug: Trospium; Drug: Placebo oral tablet

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.

Explanation for change in study outcomes: This study was designed as a mechanistic study, using the study drug as a probe, to develop a more comprehensive qualitative model of the brain's role in bladder control. We present the primary outcome of response to drug/placebo as a cross-over drug study which allows evaluation of the study drug in a clinical population, as reported in our IRB approval document STUDY19090167. The synthesis of the groups of responders and non-responders to drug or placebo is crucial to allow in depth analysis of changes in brain structure and function which will provide insight into how the brain controls the bladder. However, such analysis is necessarily qualitative, complex and challenging to convey in a context-free numerical format, such as this site. Thus, the initially entered primary outcomes of brain structure and function will be reported with full context in upcoming manuscripts.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo/Trospium; Placebo first for 12 weeks followed by Trospium for 12 weeks.	Drug: Trospium; Drug to treat overactive bladder; Other Names: Sanctura; Drug: Placebo oral tablet; Placebo tablet containing no active drug; Other Names: Placebo
Experimental: Trospium/Placebo; Trospium first for 12 weeks followed by Placebo for 12 weeks	Drug: Trospium; Drug to treat overactive bladder; Other Names: Sanctura; Drug: Placebo oral tablet; Placebo tablet containing no active drug; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder (Yes/no)	Whether reduction in number of leaks on 3-day bladder diary is at least 50%	Baseline to 12 weeks and baseline to 24 weeks

Collaborators and Investigators

• Sponsor: Becky Clarkson
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Becky Clarkson, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2020
• Primary Completion (Actual): February 28, 2025
• Study Completion (Actual): October 30, 2025

Study Registration Dates

• First Submitted: January 9, 2020
• First Submitted That Met QC Criteria: January 9, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Urinary Incontinence; Urgency urinary incontinence; Trospium
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urination Disorders; Lower Urinary Tract Symptoms; Urological Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Urinary Incontinence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Urological Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Parasympatholytics; trospium chloride
• Other Study ID Numbers: STUDY19090167; R01AG064251 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial, after de-identification may be shared with other researchers.
• IPD Sharing Time Frame: Following publication, no end date
• IPD Sharing Access Criteria: Any purpose
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No