A Pilot Study of Mirabegron and Behavioral Modification Including Pelvic Floor Exercise for Overactive Bladder in Parkinson's Disease (MAESTRO)

Study Overview
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Brief Summary
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The purpose of this study is to see if the study drug, Mirabegron, is safe and effective in treating symptoms of Overactive Bladder in people with Parkinson's Disease.

Detailed Description
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This study is a randomized 1:1 placebo-controlled 10-week study of Mirabegron as add-on therapy to an educational intervention of behavioral modification including pelvic floor exercise (PFE) in a cohort of 40 Parkinson's subjects over the age of 30 with overactive bladder (OAB). Active drug will be Mirabegron 25 mg daily with up-titration to 50 mg daily after 5 weeks. Subjects will be enrolled based on response to an overactive bladder questionnaire at visit 2. Enrolled subjects will have 4 study visits to the clinic as well as 2 phone visits. Enrolled subjects will be asked to record urinary symptoms and pelvic floor exercises in a diary at 3 separate time points for a 72 hour period.

Official Title
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A Pilot Study of Mirabegron and Behavioral Modification Including Pelvic Floor Exercise for Overactive Bladder in Parkinson's Disease. (MAESTRO)

Conditions
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Parkinsons Disease

Intervention / Treatment
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* Drug: Mirabegron
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:- Diagnosis of Parkinsons by United Kingdom brain bank criteria Age > 30 years old No change in Parkinsons medications during the 4 weeks preceding screening, with no dose changes during the study, except that PRN (as needed) doses of carbidopa/levodopa will be allowed to address periodic worsening of parkinsonian symptoms. Patient willing and able to complete micturition diary Urinary urgency (≥ 8 entries of bladder urgency score > 2) in 72hr voiding diary during screening period Micturition frequency ≥ 8 / 24hr or incontinence ≥ 2 episodes in 72hr voiding diary during screening period Use of other medication that could influence bladder function, other than those specifically prohibited (see below), will be permitted as long as the dose is stable for 4 weeks preceding screening, with no dose changes during the study. Patient expects to have valid health insurance for the duration of the study period Exclusion Criteria: Women who are breast-feeding, pregnant or have potential to become pregnant during the course of the study (fertile and unwilling/unable to use effective contraceptive measures). Cognitive deficits that in the opinion of the investigator would interfere with the subject's ability to give informed consent or perform study testing. Screening blood pressure > 165 systolic or 100 diastolic Heart rate > 100 History of allergy to Mirabegron. Screening post-void residual > 200ml Evidence of urinary tract infection at screening History of chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy, or previous or current malignant disease of the pelvic organs Intravesical botulinum toxin treatment within the previous six months of screening. Presence of Interstim device Use of indwelling catheter or self-catheterization Concurrent use of thioridazine, flecainide, propafenone, or Digoxin Concurrent use of warfarin (Coumadin) Use of one of the anti-cholinergic bladder medications specified below within 14 days of the screening visit. Subjects who have used one of these medications in the past but discontinued it at least 14 days prior to the screening visit can be enrolled. Screening estimated glomerular filtration rate (eGFR) < 60, AST ( aspartate aminotransferase ) or ALT ( alanine aminotransferase ) > 2x upper limit of normal Any other serious and/or unstable medical condition Participation in other drug studies or use of other investigational drugs within 30 days prior to Screening Visit.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mirabegron<br>1:1 randomization to receive Mirabegron 25 mg daily or placebo at visit 2. At visit 3 all subjects who have tolerated Mirabegron 25 mg daily (no adverse events on this dose) will be up-titrated to Mirabegron 50 mg daily. This will be dispensed as two 25mg tablets or, for those in the placebo arm, two placebo tablets. | Drug: Mirabegron<br>* 25 mg po daily for 32-40 days. Following up-titration to 50 mg po daily. This is pending no adverse events on the 25 mg dose.<br>* Other names: Mirabetriq;|
| Placebo Comparator: Placebo<br>1:1 randomization to receive Mirabegron 25 mg daily or placebo at visit 2. At visit 3 all subjects who have tolerated Mirabegron 25 md daily (no adverse events on this dose) will be up-titrated to Mirabegron 50 mg daily. This will be dispensed as two 25mg tablets or , for those in the placebo arm, two placebo tablets. | Drug: Placebo<br>* Placebo 25 mg po daily. Following up-titration to 50 mg po daily. This is pending no adverse events on the 25 mg dose.<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Mean Daily Overactive Bladder-Symptom Composite Score. | The primary outcome measure will be the change in the mean daily Overactive Bladder-Symptom Composite Score (OAB-SCS) from baseline (visit 2) to visit 4. The Over active Bladder- Symptom Composite Score requires subjects to record the severity of urgency of each micturition over a 72 hour period. Subject ratings ranges from 1 to 6 for each micturition as follows: 1. Not at all, 2.A little bit, 3.Somewhat 4.Quite a bit, 5. A great deal, 6. A very great deal. Maximum score depends on number of micturition episodes in the 72 hour period, as the rating of each episode is summed to get the total score. Higher scores indicate worse symptoms of overactive bladder. | 7-82 days. From visit 2 (baseline) to visit 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overactive Bladder Questionnaire Symptom Severity Scale( OAB-q) | Overactive Bladder questionnaire symptom severity scale (OAB-q), Visit 3 and Visit 4 vs. baseline Scale ranges from 8 to 48 the higher score indicating worse symptoms. | baseline (7-14 days post visit 1), visit 3( 32-40 days post visit 2) and visit 4(74-82 days post visit 2) | 
| Non- Motor Symptoms Scale (NMSS) | Non-Motor Symptoms Scale (NMSS), which includes questions about 9 different categories of non-motor symptoms in PD, including urinary symptoms; Visit 3 and Visit 4 vs. baseline. Symptoms assessed over the last month. The scale ranges from 0 to 360, with higher scores indicating worse symptoms. | baseline (7-14 days post visit 1), visit 3 (32-40 days post visit 2) and visit 4 (74-82 days post visit 2) | 
| Patient Perception of Bladder Condition | Patient Perception of Bladder Condition at Visit 3 and Visit 4 vs. baseline. the scale ranges from 1 to 6 with higher score indicating worse outcome | baseline (7-14 days post visit 1), visit 3 (32-40 days post visit 2) and visit 4 (74-82 days post visit 2) | 
| Subjects Global Impression of Change | Subject's Global Impression of Change at Visit 3 and Visit 4 vs. baseline the scale ranges from 0 to 7 with higher score indicating worse out come . | baseline (7-14 days post visit 1), visit 3 (32-40 days post visit 2) and visit 4 (74-82 days post visit 2) |