MIRROR: Study of Behavioral Modification Program and Mirabegron to Improve Urinary Urgency in Multiple Sclerosis

Sponsor

Theodore R. Brown, MD MPH (Other)

Overall Status

Completed

CT.gov ID

NCT02086188

Collaborator

Astellas Pharma Inc (Industry)

Enrollment

Location

Arms

Actual Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if treatment with Mirabegron will improve urinary urgency control beyond that achieved with pelvic floor exercises alone

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Mirabegron Drug: Placebo	Phase 4

Detailed Description

A randomized 1:1 placebo controlled 10-week study of mirabegron as add-on therapy to an educational intervention on behavioral modification including pelvic floor exercise (BM-PFE) to a cohort of 40 Multiple Sclerosis (MS) subjects with overactive bladder (OAB). Trial will last approximately 12 weeks for each subject, including screening period and treatment period.

Active drug will be mirabegron 25mg daily with optional up-titration to 50mg daily after approximately 5 weeks. Subjects will be randomized at the Baseline Visit based on recordings in a voiding diary kept for 72 continuous hours in the screening period.

Voiding diaries of a 72 hour period each will be utilized during the screening period, between Phone Visit 1 and Titration and between Phone Visit 2 and Final Visit. In the diaries, subjects will record the time of each micturition and/or urgency episode, urine volume with each void (when available), any episode of incontinence, and the severity of urgency (Overactive Bladder Symptom Composite Score, mean of 72 hour total daily cumulative score.

Primary outcome will be average daily OAB-SCS total score, Final Visit vs. Baseline. This accounts for the frequency, urgency and incontinence components of OAB.

Study Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Pilot Study of Mirabegron and Behavioral Modification Including Pelvic Floor Exercise for Overactive Bladder in Multiple Sclerosis (MIRROR)

Actual Study Start Date :

May 1, 2014

Actual Primary Completion Date :

Apr 1, 2019

Actual Study Completion Date :

Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mirabegron Mirabegron - 25mg (one tablet) taken by mouth daily with option to up-titrate to 50mg daily (two tablets) taken by mouth daily	Drug: Mirabegron see detailed information in associated Arm Description Other Names: MBG Myrbetriq
Placebo Comparator: Placebo Placebo - one tablet taken by mouth daily and two tablets taken by mouth daily if subject chooses up-titration	Drug: Placebo Sugar pill manufactured to mimic Mirabegron 25mg tablet.

Arm

Intervention/Treatment

Experimental: Mirabegron

Mirabegron - 25mg (one tablet) taken by mouth daily with option to up-titrate to 50mg daily (two tablets) taken by mouth daily

Drug: Mirabegron

see detailed information in associated Arm Description

Other Names:

MBG

Myrbetriq

Placebo Comparator: Placebo

Placebo - one tablet taken by mouth daily and two tablets taken by mouth daily if subject chooses up-titration

Drug: Placebo

Sugar pill manufactured to mimic Mirabegron 25mg tablet.

Outcome Measures

Primary Outcome Measures

Overactive Bladder Symptom Composite Score (OAB-SCS) at Baseline vs. Final Visit [after completion of study - approximately 3 years after start]
Primary outcome will be Average daily Overactive Bladder Symptom Composite Score (OAB-SCS) total score, Baseline vs. Final Visit

Secondary Outcome Measures

Overactive Bladder Symptom Composite Score (OAB-SCS) at Baseline vs. Titration Visit [after completion of study - approximately 3 years after start]
Secondary Outcome Measure based on voiding diary: Average daily Overactive Bladder Symptom Composite Score (OAB-SCS) Baseline compared to Titration Visit
Mean # of micturitions/day based on voiding diaries [after completion of study - approximately 3 years after start]
Secondary Outcome Measure based on voiding diary: Baseline vs. Titration and Final Visit: mean # of micturitions/day
Mean # of incontinence episodes/day [after completion of study - approximately 3 years after start]
Secondary Outcome Measure based on voiding diary: Baseline vs. Titration and Final Visit: Mean # of incontinence episodes/day
Mean volume voided/micturition [after completion of study - approximately 3 years after start]
Secondary Outcome Measure based on voiding diary: Baseline vs. Titration and Final Visit: Mean volume voided/micturition
Qualiveen Questionnaire [after completion of study - approximately 3 years after start]
Secondary Outcome Measures based on the Qualiveen Questionnaire at Titration Visit and Final Visit compared to Baseline
Subject Global Impression (single question) [after completion of study - approximately 3 years after start]
Secondary Outcome Measures based on the Subject Global Impression (single question) at Titration Visit and Final Visit compared to Baseline
Pelvic Floor Exercise (PFE) adherence question [after completion of study - approximately 3 years after start]
Secondary Outcome Measures based on the PFE adherence question at Titration Visit and Final Visit compared to Baseline
Bladder Management Difficulties Questionnaire - Short Form (SCI-QOL v1.0) [after completion of study - approximately 3 years after start]
Secondary Outcome Measures based on the Bladder Management Difficulties Questionnaire - Short Form (SCI-QOL v1.0) at Titration Visit and Final Visit compared to Baseline

Other Outcome Measures

Bowel Management Difficulties Questionnaire - Short Form (SCI-QOL v1.0) [after completion of study - approximately 3 years after start]
Exploratory Outcome Measures based on the Bowel Management Difficulties Questionnaire - Short Form (SCI-QOL v1.0) at Titration Visit and Final Visit compared to Baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Confirmed diagnosis of Multiple Sclerosis (MS) (no sub-type restrictions)
Age ≥18
No change in disease modifying therapy in 60 days.
Patient willing and able to complete micturition diary
Urinary urgency (8 or more entries of bladder urgency score ≥2) in 72hr voiding diary recorded during screening period
Micturition frequency ≥ 8 / day or incontinence ≥ 2 episodes in 72 hour voiding diary recorded during screening period
At least 36 hours of voiding activity recorded in 72 hour voiding diary during screening period
Non-antimuscarinic medications that are likely to influence bladder function may not be initiated between screening and study completion. They may be continued with no dose changes during the study.
Discontinued use of antimuscarinics at least two weeks prior to screening
Able to give informed consent

Exclusion Criteria:

Females 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)
Multiple Sclerosis exacerbation within 30 days of screening
Cognitive deficits that would interfere with the subject's ability to give informed consent or perform study testing
Screening blood pressure > 165 systolic or 100 diastolic
History of allergy to Mirabegron
Screening post-void residual > 200ml
Evidence of urinary tract infection at screening
Evidence 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(Mellaril® or Mellaril-S®, flecainide (Tambocor®), propafenone (Rythmol®) or digoxin (Lanoxin®)
Concurrent use of antimuscarinics: oxybutynin (Ditropan®, Ditropan XL ®), tolterodine (Detrol®, Detrol LA®), fesoterodine extended-release (Toviaz®), solifenacin (Vesicare®), trospium (Sanctura®, Sanctura XR®), darifenacin extended release (Enablex®)
Screening estimated glomerular filtration rate (eGFR) < 60, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2x upper limit of normal
Any other serious and/or unstable medical condition