Investigation of Brain Mechanisms Involved in Urgency Urinary Incontinence

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.