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

NCT04599088 | Completed

• 2 other identifiers: STUDY20080217R01AG065288
• Study Type: interventional
• Target: 207
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Urgency Urinary Incontinence

Keywords

Urinary Incontinence; Urgency urinary incontinence

Outcome Measures

Primary Outcomes (1)

• BOLD (Blood oxygen level dependent) fMRI signal contrast

  BOLD signal contrast - voxel-wise subtraction of normalized brain activity signal measure (BOLD response) during bladder fluid withdrawal from that during bladder infusion. Magnitude of BOLD contrast is then compared using ANOVA to compare the four groups (old dry/old wet/young dry/young wet). Differences are displayed as a map of t-values for each voxel of the brain, showing likelihood of statistical significance of differences. A priori regions of interest i.e. the bed nucleus of the stria terminalis (BST), pontine micturition center (PMC), periaqueductal grey (PAG), insula, medial prefrontal cortex (mPFC), dorsal anterior cingulate cortex/supplementary motor area (dACC/SMA) will be specified. Since BOLD signal represents the normalized contrast in fMRI signal between two states as a proxy for cerebral blood flow, it does not have a unit.

  20 minutes of a 1 hour MRI scan

Secondary Outcomes (6)

• Changes in brain structural integrity

  15 minutes of 1 hour MRI scan

• Changes in brain structural integrity

  15 minutes of 1 hour MRI scan

• Functional connectivity during infusion/withdrawal task

  20 minutes of 1 hour MRI scan

• Resting state analysis

  10 minutes of 1 hour MRI scan

• Differences in volume of brain structures

  10 minutes of 1 hour MRI scan

Study Arms (1)

Brain functional MRI with simplified urodynamics

EXPERIMENTAL

Females with urgency urinary incontinence

Other: Brain functional MRI with simplified urodynamics

Interventions

Brain functional MRI with simplified urodynamics OTHER

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.

Brain functional MRI with simplified urodynamics

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 'Old' (community-dwelling, mentally and functionally intact ambulatory women aged 65+ years) or 'Young' (equivalent women aged 18-45)
• 'Wet' (those who meet the International Continence Society definition of urgency urinary incontinence (urinary leakage accompanied by a sudden, strong urge to void which is difficult to defer) \>5 times per week, for 3 months despite treatment for reversible causes (e.g., Urinary tract infection) and confirmed by a mean of one episode per day of UUI on 3-day bladder diary) or 'Dry' (women without current or past UUI or other lower urinary tract symptoms.) Infrequent stress incontinence of a small amount is acceptable.
• Urge-predominant mixed incontinence is acceptable provided the subject is able to differentiate between stress incontinence (SUI - leakage that coincides instantaneously with cough, laugh, exercise) and urgency incontinence, i.e., leakage accompanied by a sudden strong urge to void that is difficult to defer.
• Those with current or previous use of anticholinergic/beta-3 agonist medications will be considered for the study if they are willing to go through a washout period of at least 4 weeks of duration.

You may not qualify if:

• Dry Groups
• Current or prior treatment for UUI
• Leakage on bladder diary not ascribed to minimal SUI (see bullet above)
• All Groups: 'Wet' or 'Dry'; 'Young' or 'Old'
• Cognitive impairment:
• MoCA\<26
• inability to perform a voiding diary/pad test
• inability to reliably take daily medication
• inability to comply with fMRI testing
• Impaired mobility
• o Timed up and go test ≥ 12 secs
• Medical instability:
• severe uncontrolled hypertension \>180mmHg systolic or \>100mmHg diastolic
• potential major changes in medical management over the course of the study period (i.e. upcoming surgery/treatment)
• frailty according to the Fried criteria

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Urinary Incontinence

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Becky Clarkson, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Assistant Professor of Medicine

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 22, 2020
• Study Start: December 14, 2020
• Primary Completion: July 31, 2025
• Study Completion: April 1, 2026
• Last Updated: May 1, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Following publication, no end date
• Access Criteria: Any purpose

Locations

US (1)