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.

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.

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.

Potential participants must be biologically female

All of the individual participant data collected during the trial, after de-identification may be shared with other researchers.

Following publication, no end date

Any purpose

While the study design is technically a cross-over design, it differs from a standard cross-over design. The design does not involve a washout period after drug administration, as part of the design is assess reversion of symptoms. Our goal is not to compare treatment to placebo, and is not designed specifically to do so. The goal of the cross-over design was only to provide a framework for the mechanistic study, and the outcomes are reported in a way that reflects that.

Adverse event data were collected from enrollment in the study (signing the consent form), to the final MRI visit (approximately 24 weeks)

Participants were asked during telephone calls up to 3 times per period, and at in person visits at the end of each period, if they experienced any side effects.

This was a mechanistic study designed to use the study drug as a probe (rather than evaluate efficacy) to understand the brain's role in bladder control. We present the primary outcome of response to drug/placebo as a cross-over drug study. The synthesis of these groups allows 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 complex and challenging to convey in a rigid format such as this.