Investigation of Brain Mechanisms Involved in Urgency Urinary Incontinence

Urgency Urinary Incontinence Clinical Trial

Official title:

Investigation of Brain Mechanisms Involved in Urgency Urinary Incontinence

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04227184
• Other study ID #: STUDY19090167
• Secondary ID: R01AG064251
• Status: Recruiting
• Phase: Phase 4
• Start date: February 13, 2020
• Est. completion date: May 30, 2025

Study information

• Verified date: February 2024
• Source: University of Pittsburgh
• Contact: Becky Clarkson, PhD
• Phone: 412-647-1270
• Email: bdc29[@]pitt.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: May 30, 2025
• Est. primary completion date: November 1, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Enuresis
• Urgency Urinary Incontinence
• Urinary Incontinence

Intervention

Drug:
• Trospium
Drug to treat overactive bladder
• Placebo oral tablet
Placebo tablet containing no active drug

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Becky Clarkson	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Structural brain changes	Change in grey and white matter volume on MRI compared between responders and non-responders to therapy/placebo. Grey matter and white matter volume of important brain structures will be compared, along with structural integrity of white matter pathways via tractography.	Baseline to 12 weeks
Primary	Structural brain changes	Change in grey and white matter volume on MRI compared between responders and non-responders to therapy/placebo. Grey matter and white matter volume of important brain structures will be compared, along with structural integrity of white matter pathways via tractography.	12 to 24 weeks
Primary	Functional brain changes	Change in brain functional response to an infusion/withdrawal protocol compared between responders and non-responders to therapy/placebo. Changes are displayed as a map of t-values for each voxel of the brain, showing likelihood of statistical significance of changes.	Baseline to 12 weeks
Primary	Functional brain changes	Change in brain functional response to an infusion/withdrawal protocol compared between responders and non-responders to therapy/placebo. Changes are displayed as a map of t-values for each voxel of the brain, showing likelihood of statistical significance of changes.	12 to 24 weeks