Investigation of Brain Mechanisms Involved in Urgency Urinary Incontinence

Study Overview
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Brief Summary
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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
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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.

Official Title
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Investigation of Brain Mechanisms Involved in Urgency Urinary Incontinence

Conditions
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Urgency Urinary Incontinence

Intervention / Treatment
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* Drug: Trospium
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 60+ years old Has UUI or urge-predominant mixed incontinence at least 5 times/ week for > 3 months despite treatment for reversible causes Exclusion Criteria: conditions/medications contraindicating trospium If currently taking anticholinergic medications (participant must refrain from anticholinergic medications for 4 weeks prior enrollment in order to be eligible) Impaired mobility or cognition sufficient to preclude following study procedures; MoCA test score <24/30; a clinically-apparent neurological condition Prolapse beyond the hymen Interstitial cystitis Spinal cord injury History of pelvic radiation or advanced uterine/bladder cancer Urethral obstruction (uroflow); PVR >200 ml Medical instability Prior UUI treatment with onabotulinum toxin or neuromodulation Drug interaction or expected medication change during the study Conditions requiring IV antibacterial prophylaxis New incontinence treatment < 3 months prior to enrollment Fecal incontinence, and symptomatic colitis/IBS Contraindications to MRI.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo/Trospium<br>Placebo first for 12 weeks followed by Trospium for 12 weeks. | Drug: Trospium<br>* Drug to treat overactive bladder<br>* Other names: Sanctura;Drug: Placebo oral tablet<br>* Placebo tablet containing no active drug<br>* Other names: Placebo;|
| Experimental: Trospium/Placebo<br>Trospium first for 12 weeks followed by Placebo for 12 weeks | Drug: Trospium<br>* Drug to treat overactive bladder<br>* Other names: Sanctura;Drug: Placebo oral tablet<br>* Placebo tablet containing no active drug<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Structural brain changes | 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. | Baseline to 12 weeks | 
| Structural brain changes | 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. | 12 to 24 weeks | 
| Functional brain changes | 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. | Baseline to 12 weeks | 
| Functional brain changes | 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. | 12 to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urinary Incontinence, Urgency urinary incontinence, Trospium