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

Phase 4

Completed

Conditions: Multiple Sclerosis

Interventions: Drug: Placebo
Drug: Mirabegron

Registration Number: NCT02086188

Lead Sponsor: Theodore R. Brown, MD MPH

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

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo - one tablet taken by mouth daily and two tablets taken by mouth daily if subject chooses up-titration
Mirabegron	Mirabegron	Mirabegron - 25mg (one tablet) taken by mouth daily with option to up-titrate to 50mg daily (two tablets) taken by mouth daily

Primary Outcome Measures

Name	Time	Method
Overactive Bladder Symptom Composite Score (OAB-SCS) at Baseline vs. Final Visit	10 weeks	Primary outcome: Overactive Bladder Symptom Composite Score (OAB-SCS) total score, average daily, Baseline vs. Final Visit The OAB-SCS measures symptoms of overactive bladder, urgency, frequency, incontinence. This is an ordinal scale is 1-5, 1 (minimum) = no urgency, 5 (maximum) = urgency incontinence. Higher values represent a worse outcome.

Secondary Outcome Measures

Name	Time	Method
Mean # of Micturitions/Day Based on Voiding Diaries	10 weeks	Secondary Outcome Measure based on voiding diary: Baseline vs Final Visit: mean # of micturitions/day
Mean # of Incontinence Episodes/Day	10 weeks	Secondary Outcome Measure based on voiding diary: Baseline vs. Final Visit: Mean # of incontinence episodes/day
Mean Volume Voided/Micturition	10 weeks	Secondary Outcome Measure based on voiding diary: Baseline vs. Final Visit: Mean volume voided/micturition
Overactive Bladder Symptom Composite Score (OAB-SCS) at Baseline vs. Titration Visit	5 weeks	Secondary Outcome Measure based on voiding diary: Average daily Overactive Bladder Symptom Composite Score (OAB-SCS) Baseline compared to Titration Visit The OAB-SCS measures symptoms of overactive bladder, urgency, frequency, incontinence. This is an ordinal scale is 1-5, 1 (minimum) = no urgency, 5 (maximum) = urgency incontinence. Higher values represent a worse outcome.
Qualiveen Questionnaire	10 weeks	Secondary Outcome Measures based on the Qualiveen Questionnaire at Final Visit compared to Baseline Qualiveen questionaire is used, including 8 questions about aspects of bladder problems. Each question is rated 0 (not at all)- 4 (extremely). Overall score is averaged (average score per question)
Subject Global Impression (Single Question)	10 weeks	Secondary Outcome Measures based on the Subject Global Impression (single question) at Final Visit compared to Baseline This is a single question: "How would you rate your level of bladder control during the past week?" 1-7 analog scale, 1 = "terrible'" 7 = "delighted."