Clinical trial NCT02086188: Study of Behavioral Modification Program and Mirabegron to Improve Urinary Urgency in Multiple Sclerosis
Official title: Pilot Study of Mirabegron and Behavioral Modification Including Pelvic Floor Exercise for Overactive Bladder in Multiple Sclerosis (MIRROR)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Overactive Bladder
Incontinence
Voiding
Bladder Urgency
Pelvic Floor Exercises
Lead sponsor: EvergreenHealth
Sponsor class: OTHER
Collaborators: name: Astellas Pharma Inc
First posted: 2014-03-13
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overactive Bladder Symptom Composite Score (OAB-SCS) at Baseline vs. Final Visit
timeFrame: 10 weeks
Secondary outcomes:
measure: Overactive Bladder Symptom Composite Score (OAB-SCS) at Baseline vs. Titration Visit
timeFrame: 5 weeks
measure: Mean # of Micturitions/Day Based on Voiding Diaries
timeFrame: 10 weeks
measure: Mean # of Incontinence Episodes/Day
timeFrame: 10 weeks
measure: Mean Volume Voided/Micturition
timeFrame: 10 weeks
measure: Qualiveen Questionnaire
timeFrame: 10 weeks
measure: Subject Global Impression (Single Question)
timeFrame: 10 weeks
Other outcomes:
Locations:
city: Kirkland
country: United States
facility: EvergreenHealth MS Center
state: Washington
Study officials:
affiliation: EvergreenHealth
name: Theodore R Brown, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: