Higher Neural Changes Following Anticholinergic, Beta 3 Agonist, or Placebo in Patients With Overactive Bladder
Primary Purpose
Overactive Bladder, Dementia, Lower Urinary Tract Symptoms
Status
Unknown status
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Anticholinergic
Beta-3 Agonists, Adrenergic
Functional magnetic resonance imaging (fMRI)
Rey Auditory Verbal Learning Test (RAVLT)
Sponsored by
About this trial
This is an interventional prevention trial for Overactive Bladder
Eligibility Criteria
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
Sites / Locations
- Houston Methodist HospitalRecruiting
- Baylor Scott and White HealthRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Active Comparator
Active Comparator
Arm Label
Placebo
Anticholinergic
Beta-3 agonists, adrenergic
Arm Description
Placebo pill identical will be identical to tablets in the other 2 arms.
Solifenacin 5 mg tablet orally once daily for 30 days
Mirabegron 25 mg tablet orally once daily for 30 days
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
Score on Rey Auditory Verbal Learning Test (RAVLT)
Baseline testing will be compared with post-intervention testing
Overactive bladder questionnaire (OAB-q)
Baseline score of this validated questionnaire will be compared with post-intervention score
Patient Perception of Bladder Condition (PPBC)
Baseline score of this validated questionnaire will be compared with post-intervention score
Full Information
NCT ID
NCT03817931
First Posted
January 24, 2019
Last Updated
April 1, 2020
Sponsor
Baylor Research Institute
Collaborators
The Methodist Hospital Research Institute, International Urogynecological Association
1. Study Identification
Unique Protocol Identification Number
NCT03817931
Brief Title
Higher Neural Changes Following Anticholinergic, Beta 3 Agonist, or Placebo in Patients With Overactive Bladder
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Unknown status
Study Start Date
August 5, 2019 (Actual)
Primary Completion Date
May 1, 2020 (Anticipated)
Study Completion Date
June 1, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baylor Research Institute
Collaborators
The Methodist Hospital Research Institute, International Urogynecological Association
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Overactive Bladder, Dementia, Lower Urinary Tract Symptoms, Incontinence, Urge
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Permuted block stratified by recruitment site
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Randomization using a random number system will be performed by the compounding pharmacy. Records linking subject number to their allocation will be kept by the pharmacy, inaccessible to the investigator, patient, care providers.
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo pill identical will be identical to tablets in the other 2 arms.
Arm Title
Anticholinergic
Arm Type
Active Comparator
Arm Description
Solifenacin 5 mg tablet orally once daily for 30 days
Arm Title
Beta-3 agonists, adrenergic
Arm Type
Active Comparator
Arm Description
Mirabegron 25 mg tablet orally once daily for 30 days
Intervention Type
Drug
Intervention Name(s)
Anticholinergic
Other Intervention Name(s)
Solifenacin, VESIcare
Intervention Description
Tablet taken once daily.
Intervention Type
Drug
Intervention Name(s)
Beta-3 Agonists, Adrenergic
Other Intervention Name(s)
Mirabegron, Myrbetriq
Intervention Description
Tablet taken once daily.
Intervention Type
Diagnostic Test
Intervention Name(s)
Functional magnetic resonance imaging (fMRI)
Intervention Description
All subjects have fMRI at baseline and again after 30 days
Intervention Type
Diagnostic Test
Intervention Name(s)
Rey Auditory Verbal Learning Test (RAVLT)
Other Intervention Name(s)
cognitive testing
Intervention Description
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.
Primary Outcome Measure Information:
Title
Functional connectivity on MRI
Description
Functional connectivity during a word recognition task will be compared within subjects from baseline and after 29+/- 1 day of intervention medication.
Time Frame
29 +/-1 days
Title
Resting state blood oxygenation level dependent (BOLD)changes
Description
During resting state, BOLD changes will be compared within subjects from baseline and after 29+/- 1 day of intervention medication.
Time Frame
29 +/-1 days
Title
Diffusion tensor imaging
Description
Fractional anisotropy and mean diffusivity from diffusion tensor images will be compared within subjects from baseline and after 29+/- 1 day of intervention medication.
Time Frame
29 +/-1 days
Secondary Outcome Measure Information:
Title
Score on Rey Auditory Verbal Learning Test (RAVLT)
Description
Baseline testing will be compared with post-intervention testing
Time Frame
30 days
Title
Overactive bladder questionnaire (OAB-q)
Description
Baseline score of this validated questionnaire will be compared with post-intervention score
Time Frame
30 days
Title
Patient Perception of Bladder Condition (PPBC)
Description
Baseline score of this validated questionnaire will be compared with post-intervention score
Time Frame
30 days
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jill M Danford, MD
Phone
2547621857
Email
highr077@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Rachel High, DO
Phone
4025257006
Email
highr077@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jill Danford, MD
Organizational Affiliation
Baylor Scott and White Health
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rose Khavari, MD
Organizational Affiliation
The Methodist Hospital Research Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rachel High, DO
Organizational Affiliation
Baylor Scott and White Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Houston Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hamida Rajab
First Name & Middle Initial & Last Name & Degree
Rose Khavai, MD
Facility Name
Baylor Scott and White Health
City
Temple
State/Province
Texas
ZIP/Postal Code
75608
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rachel High
Phone
254-724-2102
First Name & Middle Initial & Last Name & Degree
Rachel High, DO
First Name & Middle Initial & Last Name & Degree
Jill Danford, MD
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
There is not a plan.
Links:
URL
https://www.houstonmethodist.org/research/our-research/cores/translational-imaging-core-facilities/
Description
Houston Methodist Translational Imaging Center
Learn more about this trial
Higher Neural Changes Following Anticholinergic, Beta 3 Agonist, or Placebo in Patients With Overactive Bladder
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