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

Theodore R. Brown, MD MPH

Status and phase

Completed

Phase 4

Conditions

Multiple Sclerosis

Treatments

Drug: Placebo

Drug: Mirabegron

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02086188

TRB2013

Details and patient eligibility

About

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

Full 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.

Enrollment

28 patients

Sex

All

Ages

18+ years old

Volunteers

No 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