NCT04599088

Investigation of Brain Mechanisms Involved in the Urinary Continence Mechanism Associated With Aging

• Status: Active Not Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 207 (actual)
• Sponsor: University of Pittsburgh · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

Urge urinary incontinence (UUI) is a common problem in older people which vastly reduces quality of life, yet the cause and mechanism of disease are not well understood. This study will characterize brain control of the bladder in young and old continent individuals and age-matched incontinent counterparts. This will expand the investigators current knowledge of how the brain controls the bladder, how that control changes with age and disease, and suggest new targets to guide development of better treatment.

Detailed description

Current data suggest that bladder control comprises 3 cerebral circuits that maintain continence by suppressing the voiding reflex in the midbrain. In the UUI phenotype that responded to BFB (Biofeedback assisted pelvic floor muscle therapy), the mechanism involved enhancing deactivation of the first brain circuit (medial prefrontal cortex, mPFC) which resulted in less activation of the second circuit (which includes the midcingulate cortex). In the phenotype that was resistant to BFB, no brain changes were seen. Although the investigators have an emerging picture of the brain's role in UUI, the investigators have only rudimentary understanding of what is 'normal', i.e. how the brain normally controls the bladder. Moreover, the investigators do not know whether this control mechanism is the same across the lifespan, or whether it changes owing to the impact of aging. Thus, the investigators aims are to characterize the brain's normal role in bladder control in both young and old people, to determine the changes in brain structure and function that lead to bladder control failure (UUI), and to examine how such changes differ between young and old individuals. To address the aims, the investigators will utilize detailed neuroimaging to evaluate 80 asymptomatic women and 80 women with UUI, each group divided into young (18-45) and old (65+ years) individuals. The study will enable the investigators to define the brain's key structures, functional activity, and mechanisms involved in normal bladder control, and to identify the differences in these elements among those with UUI, both young and old. By elucidating the mechanisms that mediate the brain's control (and loss of control) of bladder function, the proposed study should enhance the investigators working model, deepen the understanding of the impact of aging, and identify better targets for the treatment of UUI. It may thereby enable scientists to develop novel and more effective new therapies based on the revolution in neuroscience-and more hope for UUI sufferers.

Conditions

• Urgency Urinary Incontinence

Interventions

Type	Name	Description
OTHER	Brain functional MRI with simplified urodynamics	Structural: MPRAGE provides a structural image, which is used for coregistration of subjects. Structural scans are then performed including Diffusion Spectrum Imaging (DSI; microstructural), and Fluid-attenuated inversion recovery (FLAIR; white matter specific) scans. Functional: With about 50 ml in the bladder, resting state functional BOLD measurements are made, followed by functional whole-brain images while a small amount of saline is infused and withdrawn from the bladder, in 2 blocks of 4 repetitions each. Each repetition starts with a 12-scan pause, followed by infusion (6 scans = 12 s), pause (6 scans), and withdrawal (6 scans). Each block of 4 repetitions is completed by a 6 scan pause during which scanning continues. 24 ml is infused at 120 ml/min, and slightly less is withdrawn to avoid accommodation.This is repeated on an empty and full bladder along with a resting state image.

Timeline

• Start date: 2020-12-14
• Primary completion: 2025-07-31
• Completion: 2026-04-01
• First posted: 2020-10-22
• Last updated: 2026-02-17

Locations

1 site across 1 country: United States