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

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinsons Disease
• Intervention / Treatment: Drug: Mirabegron; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Washington
    • Kirkland, Washington, United States, 98034
      • Evergreenhealth Booth Gardner Parkinsons Care Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Mirabegron; 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; 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.; Other Names: Mirabetriq
Placebo Comparator: Placebo; 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; Placebo 25 mg po daily. Following up-titration to 50 mg po daily. This is pending no adverse events on the 25 mg dose.; Other Names: sugar pill

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Daily OAB-SCS Visit 3 vs Baseline	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.	baseline (7-14 days post visit 1) and visit 3 (32-40 days post visit 2)
Change in Mean Number of Incontinence Episodes Per 24 Hours	Subjects recorded in a 72-hour micturition diary the number of episodes of urinary incontinence, and this is averaged per 24 hours. Higher scores indicate more episodes of incontinence and thus worse outcome.	baseline vs visit 3 (32-40 days post baseline) and baseline vs. visit 4 ((74-82 days post visit 2)

Collaborators and Investigators

• Sponsor: Daniel Burdick, MD
• Collaborators: Astellas Pharma US, Inc.
• Investigators: Principal Investigator: Daniel J Burdick, MD, Evergreen Health; Principal Investigator: Pinky Agarwal, MD, Evergreen Health

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: March 7, 2014
• First Submitted That Met QC Criteria: March 18, 2014
• First Posted (Estimate): March 20, 2014

Study Record Updates

• Last Update Posted (Actual): August 16, 2021
• Last Update Submitted That Met QC Criteria: July 22, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Urinary Bladder, Overactive; Parkinson Disease; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Mirabegron
• Other Study ID Numbers: DBPA-2013-01