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

Multiple Sclerosis Clinical Trial

— MIRROR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02086188
• Other study ID #: TRB2013
• Status: Completed
• Phase: Phase 4
• Start date: May 2014
• Est. completion date: June 2019

Study information

• Verified date: September 2023
• Source: EvergreenHealth
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: June 2019
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Mirabegron
see detailed information in associated Arm Description
• Placebo
Sugar pill manufactured to mimic Mirabegron 25mg tablet.

Locations

Country	Name	City	State
United States	EvergreenHealth MS Center	Kirkland	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Theodore R. Brown, MD MPH	Astellas Pharma Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overactive Bladder Symptom Composite Score (OAB-SCS) at Baseline vs. Final Visit	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.	10 weeks
Secondary	Overactive Bladder Symptom Composite Score (OAB-SCS) at Baseline vs. Titration Visit	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.	5 weeks
Secondary	Mean # of Micturitions/Day Based on Voiding Diaries	Secondary Outcome Measure based on voiding diary: Baseline vs Final Visit: mean # of micturitions/day	10 weeks
Secondary	Mean # of Incontinence Episodes/Day	Secondary Outcome Measure based on voiding diary: Baseline vs. Final Visit: Mean # of incontinence episodes/day	10 weeks
Secondary	Mean Volume Voided/Micturition	Secondary Outcome Measure based on voiding diary: Baseline vs. Final Visit: Mean volume voided/micturition	10 weeks
Secondary	Qualiveen Questionnaire	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)	10 weeks
Secondary	Subject Global Impression (Single Question)	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."	10 weeks