<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03817931</url>
  </required_header>
  <id_info>
    <org_study_id>160362</org_study_id>
    <nct_id>NCT03817931</nct_id>
  </id_info>
  <brief_title>Higher Neural Changes Following Anticholinergic, Beta 3 Agonist, or Placebo in Patients With Overactive Bladder</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Baylor Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Methodist Hospital Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>International Urogynecological Association</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Baylor Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Women presenting with overactive bladder symptoms will be randomized to one of 3 arms&#xD;
      (anticholinergic, beta-3 agonist, placebo). They will undergo baseline cognitive testing,&#xD;
      functional MRI of the brain. Cognitive testing and functional MRI will be repeated after&#xD;
      taking their double blinded intervention for 30 days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Women presenting to the urology clinic with complaints of urinary urgency, frequency in the&#xD;
      absence of urinary tract infection or other obvious pathology will be screened for&#xD;
      inclusion/exclusion criteria. Qualifying subjects will be consented.&#xD;
&#xD;
      Baseline health information, bladder symptom questionnaires (Overactive&#xD;
      Bladder-questionnaire(OABq), Patient Perception of Bladder Condition (PPBC)), Personal Health&#xD;
      Questionnaire-9 (PHQ-9),Hamilton Anxiety Rating Scale (HAM-A), Montreal cognitive assessment&#xD;
      (MoCA) will be given. If baseline depression (PHQ-9 score 15 or greater),dementia (MoCA score&#xD;
      25 or less), anxiety (HAM-A score 25-30) are noted the subject is excluded. 15 patients will&#xD;
      be recruited from Baylor Scott &amp; White Health Urology clinic, and 15 patients will be&#xD;
      recruited from Houston Methodist Urology clinic.&#xD;
&#xD;
      They will schedule a date within 1 month for the Rey Auditory Verbal Learning Test (RAVLT)&#xD;
      and brain functional MRI (fMRI). RAVLT test is performed, followed by resting state fMRI and&#xD;
      memory task during fMRI. Vials of medication will be distributed. Vials will be labeled 1-30&#xD;
      and will contain 30 tablets each. The anticholinergic and beta-3 agonist tablets will be&#xD;
      encapsulated to look identical to the placebo tablet. Subjects will be reimbursed at this&#xD;
      visit. fMRI images at baseline and post-intervention will be analyzed by a radiologist for&#xD;
      incidental findings.&#xD;
&#xD;
      One week and two weeks after initiating their tablets, phone interviews will inquire about&#xD;
      pill count, side effects, and any new medications. Follow up testing date will be scheduled&#xD;
      during the call. The same questions will be repeated at completion of the tablets (30 days&#xD;
      after initiation).&#xD;
&#xD;
      At completion of the tablets, subjects return to Houston Methodist for repeat RAVLT and fMRI.&#xD;
      Subjects will be reimbursed the other half of their compensation at this visit.&#xD;
&#xD;
      An expert physicist will analyze the BOLD signal intensity and FC pattern in a priori&#xD;
      selected regions of interest before and after interventions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 5, 2019</start_date>
  <completion_date type="Anticipated">June 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Permuted block stratified by recruitment site</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <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.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Functional connectivity on MRI</measure>
    <time_frame>29 +/-1 days</time_frame>
    <description>Functional connectivity during a word recognition task will be compared within subjects from baseline and after 29+/- 1 day of intervention medication.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Resting state blood oxygenation level dependent (BOLD)changes</measure>
    <time_frame>29 +/-1 days</time_frame>
    <description>During resting state, BOLD changes will be compared within subjects from baseline and after 29+/- 1 day of intervention medication.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Diffusion tensor imaging</measure>
    <time_frame>29 +/-1 days</time_frame>
    <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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Score on Rey Auditory Verbal Learning Test (RAVLT)</measure>
    <time_frame>30 days</time_frame>
    <description>Baseline testing will be compared with post-intervention testing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overactive bladder questionnaire (OAB-q)</measure>
    <time_frame>30 days</time_frame>
    <description>Baseline score of this validated questionnaire will be compared with post-intervention score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Perception of Bladder Condition (PPBC)</measure>
    <time_frame>30 days</time_frame>
    <description>Baseline score of this validated questionnaire will be compared with post-intervention score</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Overactive Bladder</condition>
  <condition>Dementia</condition>
  <condition>Lower Urinary Tract Symptoms</condition>
  <condition>Incontinence, Urge</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo pill identical will be identical to tablets in the other 2 arms.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anticholinergic</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Solifenacin 5 mg tablet orally once daily for 30 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Beta-3 agonists, adrenergic</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Mirabegron 25 mg tablet orally once daily for 30 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anticholinergic</intervention_name>
    <description>Tablet taken once daily.</description>
    <arm_group_label>Anticholinergic</arm_group_label>
    <other_name>Solifenacin</other_name>
    <other_name>VESIcare</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Beta-3 Agonists, Adrenergic</intervention_name>
    <description>Tablet taken once daily.</description>
    <arm_group_label>Beta-3 agonists, adrenergic</arm_group_label>
    <other_name>Mirabegron</other_name>
    <other_name>Myrbetriq</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Functional magnetic resonance imaging (fMRI)</intervention_name>
    <description>All subjects have fMRI at baseline and again after 30 days</description>
    <arm_group_label>Anticholinergic</arm_group_label>
    <arm_group_label>Beta-3 agonists, adrenergic</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Rey Auditory Verbal Learning Test (RAVLT)</intervention_name>
    <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.</description>
    <arm_group_label>Anticholinergic</arm_group_label>
    <arm_group_label>Beta-3 agonists, adrenergic</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>cognitive testing</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female patients of age 50 to 90 years old with OAB as defined by the International&#xD;
             Continence Society (Urgency with or without urge incontinence, usually with frequency&#xD;
             and nocturia in the absence of urinary tract infection or other obvious pathology) who&#xD;
             report that symptoms cause moderate problems using the PPBC.&#xD;
&#xD;
          -  English-speaking and able to consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Males are excluded to eliminate prostate pathology and urethral strictures, as well as&#xD;
             possible bias of gender differences on fMRI.&#xD;
&#xD;
          -  Subjects with moderately severe or severe depression (screening score of 15 or more)&#xD;
             on the Personal Health Questionnaire-9 (PHQ-9)&#xD;
&#xD;
          -  Subjects with moderate to severe anxiety (screening score 25-30) on the Hamilton&#xD;
             Anxiety Rating Scale (HAM-A)&#xD;
&#xD;
          -  A screening score indicating below normal cognitive function at baseline (score of 25&#xD;
             or less) on the montreal cognitive assessment.&#xD;
&#xD;
          -  Subjects with neurologic disorders, dementia, prior cerebrovascular accident,&#xD;
             neurogenic bladder or post-void residual greater than 250 mL&#xD;
&#xD;
          -  Anticholinergics for OAB or beta 3 agonists use for treatment of OAB in the preceding&#xD;
             six months prior to enrollment&#xD;
&#xD;
          -  Pregnant or planning to become pregnant in the next six months, or current&#xD;
             breastfeeding&#xD;
&#xD;
          -  The inability to undergo MRI&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jill Danford, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Baylor Scott and White Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rose Khavari, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Methodist Hospital Research Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rachel High, DO</last_name>
    <role>Principal Investigator</role>
    <affiliation>Baylor Scott and White Health</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jill M Danford, MD</last_name>
    <phone>2547621857</phone>
    <email>highr077@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rachel High, DO</last_name>
    <phone>4025257006</phone>
    <email>highr077@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Houston Methodist Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hamida Rajab</last_name>
    </contact>
    <investigator>
      <last_name>Rose Khavai, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Baylor Scott and White Health</name>
      <address>
        <city>Temple</city>
        <state>Texas</state>
        <zip>75608</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rachel High</last_name>
      <phone>254-724-2102</phone>
    </contact>
    <investigator>
      <last_name>Rachel High, DO</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jill Danford, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.houstonmethodist.org/research/our-research/cores/translational-imaging-core-facilities/</url>
    <description>Houston Methodist Translational Imaging Center</description>
  </link>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>April 1, 2020</last_update_submitted>
  <last_update_submitted_qc>April 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 3, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urinary Bladder, Overactive</mesh_term>
    <mesh_term>Urinary Incontinence, Urge</mesh_term>
    <mesh_term>Lower Urinary Tract Symptoms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Solifenacin Succinate</mesh_term>
    <mesh_term>Mirabegron</mesh_term>
    <mesh_term>Cholinergic Antagonists</mesh_term>
    <mesh_term>Adrenergic beta-3 Receptor Agonists</mesh_term>
    <mesh_term>Adrenergic Agents</mesh_term>
    <mesh_term>Adrenergic Agonists</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is not a plan.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03817931
org study id: 160362
nct id: NCT03817931
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Permuted block stratified by recruitment site
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes 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.
measure: Functional connectivity on MRI
time frame: 29 +/-1 days
description: Functional connectivity during a word recognition task will be compared within subjects from baseline and after 29+/- 1 day of intervention medication.
measure: Resting state blood oxygenation level dependent (BOLD)changes
time frame: 29 +/-1 days
description: During resting state, BOLD changes will be compared within subjects from baseline and after 29+/- 1 day of intervention medication.
measure: Diffusion tensor imaging
time frame: 29 +/-1 days
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.
measure: Score on Rey Auditory Verbal Learning Test (RAVLT)
time frame: 30 days
description: Baseline testing will be compared with post-intervention testing
measure: Overactive bladder questionnaire (OAB-q)
time frame: 30 days
description: Baseline score of this validated questionnaire will be compared with post-intervention score
measure: Patient Perception of Bladder Condition (PPBC)
time frame: 30 days
description: Baseline score of this validated questionnaire will be compared with post-intervention score
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo pill identical will be identical to tablets in the other 2 arms.
arm group label: Anticholinergic
arm group type: Active Comparator
description: Solifenacin 5 mg tablet orally once daily for 30 days
arm group label: Beta-3 agonists, adrenergic
arm group type: Active Comparator
description: Mirabegron 25 mg tablet orally once daily for 30 days
intervention type: Drug
intervention name: Anticholinergic
description: Tablet taken once daily.
arm group label: Anticholinergic
other name: Solifenacin
other name: VESIcare
intervention type: Drug
intervention name: Beta-3 Agonists, Adrenergic
description: Tablet taken once daily.
arm group label: Beta-3 agonists, adrenergic
other name: Mirabegron
other name: Myrbetriq
intervention type: Diagnostic Test
intervention name: Functional magnetic resonance imaging (fMRI)
description: All subjects have fMRI at baseline and again after 30 days
arm group label: Anticholinergic
arm group label: Beta-3 agonists, adrenergic
arm group label: Placebo
intervention type: Diagnostic Test
intervention name: Rey Auditory Verbal Learning Test (RAVLT)
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.
arm group label: Anticholinergic
arm group label: Beta-3 agonists, adrenergic
arm group label: Placebo
other name: cognitive testing
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jill Danford, MD
role: Principal Investigator
affiliation: Baylor Scott and White Health
last name: Rose Khavari, MD
role: Principal Investigator
affiliation: The Methodist Hospital Research Institute
last name: Rachel High, DO
role: Principal Investigator
affiliation: Baylor Scott and White Health
last name: Jill M Danford, MD
phone: 2547621857
email: highr077@gmail.com
last name: Rachel High, DO
phone: 4025257006
email: highr077@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: United States
url: https://www.houstonmethodist.org/research/our-research/cores/translational-imaging-core-facilities/
description: Houston Methodist Translational Imaging Center
responsible party type: Sponsor
mesh term: Urinary Bladder, Overactive
mesh term: Urinary Incontinence, Urge
mesh term: Lower Urinary Tract Symptoms
mesh term: Solifenacin Succinate
mesh term: Mirabegron
mesh term: Cholinergic Antagonists
mesh term: Adrenergic beta-3 Receptor Agonists
mesh term: Adrenergic Agents
mesh term: Adrenergic Agonists
sharing ipd: No
ipd description: There is not a plan.