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

NCT03817931 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: 160362
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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.

Conditions

Overactive Bladder; Dementia; Lower Urinary Tract Symptoms; Incontinence, Urge

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• Score on Rey Auditory Verbal Learning Test (RAVLT)

  30 days

• Overactive bladder questionnaire (OAB-q)

  30 days

• Patient Perception of Bladder Condition (PPBC)

  30 days

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo pill identical will be identical to tablets in the other 2 arms.

Diagnostic Test: Functional magnetic resonance imaging (fMRI); Diagnostic Test: Rey Auditory Verbal Learning Test (RAVLT)

Anticholinergic

ACTIVE COMPARATOR

Solifenacin 5 mg tablet orally once daily for 30 days

Drug: Anticholinergic; Diagnostic Test: Functional magnetic resonance imaging (fMRI); Diagnostic Test: Rey Auditory Verbal Learning Test (RAVLT)

Beta-3 agonists, adrenergic

ACTIVE COMPARATOR

Mirabegron 25 mg tablet orally once daily for 30 days

Drug: Beta-3 Agonists, Adrenergic; Diagnostic Test: Functional magnetic resonance imaging (fMRI); Diagnostic Test: Rey Auditory Verbal Learning Test (RAVLT)

Interventions

Anticholinergic DRUG

Tablet taken once daily.

Also known as: Solifenacin, VESIcare

Anticholinergic

Beta-3 Agonists, Adrenergic DRUG

Tablet taken once daily.

Also known as: Mirabegron, Myrbetriq

Beta-3 agonists, adrenergic

Functional magnetic resonance imaging (fMRI) DIAGNOSTIC_TEST

All subjects have fMRI at baseline and again after 30 days

Anticholinergic; Beta-3 agonists, adrenergic; Placebo

Rey Auditory Verbal Learning Test (RAVLT) DIAGNOSTIC_TEST

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.

Also known as: cognitive testing

Anticholinergic; Beta-3 agonists, adrenergic; Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baylor Research Institute: lead
• The Methodist Hospital Research Institute: collaborator
• International Urogynecological Association: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Baylor Scott and White Health

Temple, Texas, 75608, United States

Location

Related Publications (1)

• Stoniute A, Madhuvrata P, Still M, Barron-Millar E, Nabi G, Omar MI. Oral anticholinergic drugs versus placebo or no treatment for managing overactive bladder syndrome in adults. Cochrane Database Syst Rev. 2023 May 9;5(5):CD003781. doi: 10.1002/14651858.CD003781.pub3.

  PMID: 37160401 DERIVED

Related Links

• Houston Methodist Translational Imaging Center

MeSH Terms

Conditions

Urinary Bladder, Overactive; Dementia; Lower Urinary Tract Symptoms; Urinary Incontinence, Urge

Interventions

Cholinergic Antagonists; Solifenacin Succinate; Adrenergic beta-3 Receptor Agonists; mirabegron; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Urinary Incontinence; Urination Disorders

Intervention Hierarchy (Ancestors)

Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Jill Danford, MD

  Baylor Scott and White Health

  PRINCIPAL INVESTIGATOR

• Rose Khavari, MD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

• Rachel High, DO

  Baylor Scott and White Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Permuted block stratified by recruitment site

Study Record Dates

• First Submitted: January 24, 2019
• First Posted: January 28, 2019
• Study Start: August 5, 2019
• Primary Completion: February 2, 2022
• Study Completion: February 26, 2022
• Last Updated: February 2, 2024

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)