Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, Overactive Bladder, Incontinence, Voiding, Bladder Urgency, Pelvic Floor Exercises
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.
Interventions
DRUGMirabegron
see detailed information in associated Arm Description
DRUGPlacebo
Sugar pill manufactured to mimic Mirabegron 25mg tablet.
Sponsors
Astellas Pharma Inc
Theodore R. Brown, MD MPH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| Mean Volume Voided/Micturition | 10 weeks | Secondary Outcome Measure based on voiding diary: Baseline vs. Final Visit: Mean volume voided/micturition |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mirabegron Mirabegron - 25mg (one tablet) taken by mouth daily with option to up-titrate to 50mg daily (two tablets) taken by mouth daily
Mirabegron: see detailed information in associated Arm Description | 14 |
| Placebo Placebo - one tablet taken by mouth daily and two tablets taken by mouth daily if subject chooses up-titration
Placebo: Sugar pill manufactured to mimic Mirabegron 25mg tablet. | 14 |
| Total | 28 |
Baseline characteristics
| Characteristic | Mirabegron | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 55 years | 53 years | 50 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 28 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 27 Participants | 13 Participants |
| Region of Enrollment United States | 14 participants | 28 participants | 14 participants |
| Sex: Female, Male Female | 13 Participants | 25 Participants | 12 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 6 / 14 | 4 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 |
Outcome results
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.
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Overactive Bladder Symptom Composite Score (OAB-SCS) at Baseline vs. Final Visit | 3.01 score on a scale | Standard Deviation 0.48 |
| Placebo | Overactive Bladder Symptom Composite Score (OAB-SCS) at Baseline vs. Final Visit | 2.56 score on a scale | Standard Deviation 0.84 |
Secondary
Mean # of Incontinence Episodes/Day
Secondary Outcome Measure based on voiding diary: Baseline vs. Final Visit: Mean # of incontinence episodes/day
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Mean # of Incontinence Episodes/Day | 0.7 Incontinence Episodes/Day | Standard Deviation 1.09 |
| Placebo | Mean # of Incontinence Episodes/Day | 1.05 Incontinence Episodes/Day | Standard Deviation 2.82 |
p-value: 0.1723ANCOVA
Secondary
Mean # of Micturitions/Day Based on Voiding Diaries
Secondary Outcome Measure based on voiding diary: Baseline vs Final Visit: mean # of micturitions/day
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Mean # of Micturitions/Day Based on Voiding Diaries | 6.82 micturitions/day | Standard Deviation 2.2 |
| Placebo | Mean # of Micturitions/Day Based on Voiding Diaries | 8.72 micturitions/day | Standard Deviation 3.14 |
p-value: 0.4271ANCOVA
Secondary
Mean Volume Voided/Micturition
Secondary Outcome Measure based on voiding diary: Baseline vs. Final Visit: Mean volume voided/micturition
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Mean Volume Voided/Micturition | 356 ml/micturition | Standard Deviation 153 |
| Placebo | Mean Volume Voided/Micturition | 282 ml/micturition | Standard Deviation 174 |
p-value: 0.634ANCOVA
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.
Time frame: 5 weeks
Population: MS patients with overactive bladder
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Overactive Bladder Symptom Composite Score (OAB-SCS) at Baseline vs. Titration Visit | 2.8 score on a scale | Standard Deviation 0.64 |
| Placebo | Overactive Bladder Symptom Composite Score (OAB-SCS) at Baseline vs. Titration Visit | 2.23 score on a scale | Standard Deviation 0.72 |
p-value: 0.1911ANCOVA
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)
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Qualiveen Questionnaire | 0.96 score on a scale | Standard Deviation 0.84 |
| Placebo | Qualiveen Questionnaire | 0.71 score on a scale | Standard Deviation 0.63 |
p-value: 0.0091ANCOVA
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.
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Subject Global Impression (Single Question) | 5.71 score on a scale | Standard Deviation 1.14 |
| Placebo | Subject Global Impression (Single Question) | 4.86 score on a scale | Standard Deviation 1.29 |