Higher Neural Changes Following Anticholinergic, Beta 3 Agonist, or Placebo in Patients With Overactive Bladder

Higher Neural and Cognitive Changes Following Anticholinergic Versus Beta 3 Agonist Versus Placebo Treatments in Female Patients With Overactive Bladder: a Multicenter Randomized Controlled Pilot Trial

Women presenting with overactive bladder symptoms will be randomized to one of 3 arms (anticholinergic, beta-3 agonist, placebo). They will undergo baseline cognitive testing, functional MRI of the brain. Cognitive testing and functional MRI will be repeated after taking their double blinded intervention for 30 days.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder; Lower Urinary Tract Symptoms; Dementia; Incontinence, Urge
• Intervention / Treatment: Diagnostic test: Functional magnetic resonance imaging (fMRI); Diagnostic test: Rey Auditory Verbal Learning Test (RAVLT); Drug: Anticholinergic; Drug: Beta-3 Agonists, Adrenergic

Detailed Description

Women presenting to the urology clinic with complaints of urinary urgency, frequency in the absence of urinary tract infection or other obvious pathology will be screened for inclusion/exclusion criteria. Qualifying subjects will be consented.

Baseline health information, bladder symptom questionnaires (Overactive Bladder-questionnaire(OABq), Patient Perception of Bladder Condition (PPBC)), Personal Health Questionnaire-9 (PHQ-9),Hamilton Anxiety Rating Scale (HAM-A), Montreal cognitive assessment (MoCA) will be given. If baseline depression (PHQ-9 score 15 or greater),dementia (MoCA score 25 or less), anxiety (HAM-A score 25-30) are noted the subject is excluded. 15 patients will be recruited from Baylor Scott & White Health Urology clinic, and 15 patients will be recruited from Houston Methodist Urology clinic.

They will schedule a date within 1 month for the Rey Auditory Verbal Learning Test (RAVLT) and brain functional MRI (fMRI). RAVLT test is performed, followed by resting state fMRI and memory task during fMRI. Vials of medication will be distributed. Vials will be labeled 1-30 and will contain 30 tablets each. The anticholinergic and beta-3 agonist tablets will be encapsulated to look identical to the placebo tablet. Subjects will be reimbursed at this visit. fMRI images at baseline and post-intervention will be analyzed by a radiologist for incidental findings.

One week and two weeks after initiating their tablets, phone interviews will inquire about pill count, side effects, and any new medications. Follow up testing date will be scheduled during the call. The same questions will be repeated at completion of the tablets (30 days after initiation).

At completion of the tablets, subjects return to Houston Methodist for repeat RAVLT and fMRI. Subjects will be reimbursed the other half of their compensation at this visit.

An expert physicist will analyze the BOLD signal intensity and FC pattern in a priori selected regions of interest before and after interventions.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jill M Danford, MD; Phone Number: 2547621857; Email: highr077@gmail.com
• Study Contact Backup: Name: Rachel High, DO; Phone Number: 4025257006; Email: highr077@gmail.com

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Temple, Texas, United States, 75608
      • Baylor Scott and White Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Female patients of age 50 to 90 years old with OAB as defined by the International Continence Society (Urgency with or without urge incontinence, usually with frequency and nocturia in the absence of urinary tract infection or other obvious pathology) who report that symptoms cause moderate problems using the PPBC.
• English-speaking and able to consent

Exclusion Criteria:

• Males are excluded to eliminate prostate pathology and urethral strictures, as well as possible bias of gender differences on fMRI.
• Subjects with moderately severe or severe depression (screening score of 15 or more) on the Personal Health Questionnaire-9 (PHQ-9)
• Subjects with moderate to severe anxiety (screening score 25-30) on the Hamilton Anxiety Rating Scale (HAM-A)
• A screening score indicating below normal cognitive function at baseline (score of 25 or less) on the montreal cognitive assessment.
• Subjects with neurologic disorders, dementia, prior cerebrovascular accident, neurogenic bladder or post-void residual greater than 250 mL
• Anticholinergics for OAB or beta 3 agonists use for treatment of OAB in the preceding six months prior to enrollment
• Pregnant or planning to become pregnant in the next six months, or current breastfeeding
• The inability to undergo MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo pill identical will be identical to tablets in the other 2 arms.	Diagnostic test: Functional magnetic resonance imaging (fMRI); All subjects have fMRI at baseline and again after 30 days; Diagnostic test: Rey Auditory Verbal Learning Test (RAVLT); All subjects have RAVLT at baseline and again after 30 days. RAVLT evaluates: short-term auditory-verbal memory, rate of learning, learning strategies, retroactive, and proactive interference, presence of confabulation of confusion in memory processes, retention of information, and differences between learning and retrieval.; Other Names: cognitive testing
Active Comparator: Anticholinergic; Solifenacin 5 mg tablet orally once daily for 30 days	Diagnostic test: Functional magnetic resonance imaging (fMRI); All subjects have fMRI at baseline and again after 30 days; Diagnostic test: Rey Auditory Verbal Learning Test (RAVLT); All subjects have RAVLT at baseline and again after 30 days. RAVLT evaluates: short-term auditory-verbal memory, rate of learning, learning strategies, retroactive, and proactive interference, presence of confabulation of confusion in memory processes, retention of information, and differences between learning and retrieval.; Other Names: cognitive testing; Drug: Anticholinergic; Tablet taken once daily.; Other Names: VESIcare; Solifenacin
Active Comparator: Beta-3 agonists, adrenergic; Mirabegron 25 mg tablet orally once daily for 30 days	Diagnostic test: Functional magnetic resonance imaging (fMRI); All subjects have fMRI at baseline and again after 30 days; Diagnostic test: Rey Auditory Verbal Learning Test (RAVLT); All subjects have RAVLT at baseline and again after 30 days. RAVLT evaluates: short-term auditory-verbal memory, rate of learning, learning strategies, retroactive, and proactive interference, presence of confabulation of confusion in memory processes, retention of information, and differences between learning and retrieval.; Other Names: cognitive testing; Drug: Beta-3 Agonists, Adrenergic; Tablet taken once daily.; Other Names: Myrbetriq; Mirabegron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional connectivity on MRI	Functional connectivity during a word recognition task will be compared within subjects from baseline and after 29+/- 1 day of intervention medication.	29 +/-1 days
Resting state blood oxygenation level dependent (BOLD)changes	During resting state, BOLD changes will be compared within subjects from baseline and after 29+/- 1 day of intervention medication.	29 +/-1 days
Diffusion tensor imaging	Fractional anisotropy and mean diffusivity from diffusion tensor images will be compared within subjects from baseline and after 29+/- 1 day of intervention medication.	29 +/-1 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Score on Rey Auditory Verbal Learning Test (RAVLT)	Baseline testing will be compared with post-intervention testing	30 days
Overactive bladder questionnaire (OAB-q)	Baseline score of this validated questionnaire will be compared with post-intervention score	30 days
Patient Perception of Bladder Condition (PPBC)	Baseline score of this validated questionnaire will be compared with post-intervention score	30 days

Collaborators and Investigators

• Sponsor: Baylor Research Institute
• Collaborators: The Methodist Hospital Research Institute; International Urogynecological Association
• Investigators: Principal Investigator: Jill Danford, MD, Baylor Scott and White Health; Principal Investigator: Rachel High, DO, Baylor Scott and White Health; Principal Investigator: Rose Khavari, MD, The Methodist Hospital Research Institute

Publications and helpful links

Helpful Links

• Houston Methodist Translational Imaging Center

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2019
• Primary Completion (Actual): February 2, 2022
• Study Completion (Actual): February 26, 2022

Study Registration Dates

• First Submitted: January 24, 2019
• First Submitted That Met QC Criteria: January 24, 2019
• First Posted (Actual): January 28, 2019

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Urological Manifestations; Urination Disorders; Urinary Incontinence; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder, Overactive; Lower Urinary Tract Symptoms; Urinary Incontinence, Urge; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Agents; Urological Agents; Adrenergic beta-Agonists; Adrenergic Agonists; Mirabegron; Solifenacin Succinate; Adrenergic Agents; Cholinergic Antagonists; Adrenergic beta-3 Receptor Agonists
• Other Study ID Numbers: 160362

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes