Urgency Urinary IncontinenceNCT04599088
Investigation of Brain Mechanisms Involved in the Urinary Continence Mechanism Associated With Aging
A study testing Brain functional MRI with simplified urodynamics in people with Urgency Urinary Incontinence, run by University of Pittsburgh at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Urgency Urinary Incontinence
- What is being tested?
- Brain functional MRI with simplified urodynamics
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 217 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Dec 2020to 1 Apr 2026
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- '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.
Who cannot join
- 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
Show all 41Show fewer
- 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
- MRI incompatibility:
- contraindicated metal implants
- claustrophobia
- unidentified/untested compatibility of metal implants
- Medication incompatibility:
- allergy to study medication (all prophylactic antibiotic choices)
- interaction of prophylactic antibiotic choices with current medications
- expected change in medication during the study
- Neurological conditions:
- spinal cord injury;
- multiple sclerosis
- clinically apparent lesions (e.g. lacunae associated with stroke)
- prior stroke
- Parkinson's Disease/ALS/MSA
- any clinically apparent neurological condition
- Lower urinary tract comorbidities/treatment:
- history of pelvic irradiation
- bladder or advanced uterine cancer
- possible urethral obstruction (advanced prolapse [POP-Q>II] or Qmax<12 ml/s on free flow)
- urinary retention (PVR >200 ml)
- Interstitial Cystitis/Bladder Pain Syndrome
- artificial sphincter implant
- Botox treatment for UUI within 1 year
- Neuromodulation treatment for UUI
- Other comorbidities:
- uncontrolled depression (PHQ-9 ≥10)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
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.
Read the 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
- Being tested
- Brain functional MRI with simplified urodynamics
- Keywords
- Urinary Incontinence, Urgency urinary incontinence
- Medical subject headings
- Urinary Incontinence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brain functional MRI with simplified urodynamicsOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Brain functional MRI with simplified urodynamics | Experimental | Females with urgency urinary incontinence Receives: Other: Brain functional MRI with simplified urodynamics |
What is being measured
The primary outcome is the main question the study is designed to answer.
BOLD (Blood Oxygen Level Dependent) fMRI Signal Contrast - mPFC
BOLD signal contrast - voxel-wise subtraction of normalized brain activity signal measure (BOLD response) during bladder fluid withdrawal from that during bladder infusion in the a priori defined mPFC (medial prefrontal cortex) region. 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.
The beta value represents the amplitude of the BOLD signal difference between the two conditions. A larger beta value represents a larger difference in activity. Negative values represent greater activity in the 'withdrawal' condition.
Measured: Baseline
BOLD (Blood Oxygen Level Dependent) fMRI Signal Contrast - Left Insula
BOLD signal contrast - voxel-wise subtraction of normalized brain activity signal measure (BOLD response) during bladder fluid withdrawal from that during bladder infusion in the a priori defined insula region. 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.
The beta value represents the amplitude of the BOLD signal difference between the two conditions. A larger beta value represents a larger difference in activity. Negative values represent greater activity in the 'withdrawal' condition.
Measured: Baseline
BOLD (Blood Oxygen Level Dependent) fMRI Signal Contrast - dACC
BOLD signal contrast - voxel-wise subtraction of normalized brain activity signal measure (BOLD response) during bladder fluid withdrawal from that during bladder infusion in the a priori defined dACC (dorsal anterior cingulate cortex) region. 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.
The beta value represents the amplitude of the BOLD signal difference between the two conditions. A larger beta value represents a larger difference in activity. Negative values represent greater activity in the 'withdrawal' condition.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2020
- Study start14 Dec 2020
- Primary completion31 Jul 2025
- Study completion1 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Urgency Urinary IncontinenceStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 217 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Becky Clarkson, University of Pittsburgh
- Investigators
- Becky Clarkson, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04599088
- Sponsor's protocol ID
- STUDY20080217
- Other IDs
- R01AG065288
- Status last verified
- Jul 2026
- First submitted
- 1 Oct 2020
- Last updated
- 5 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial, after de-identification may be shared with other researchers.