Clinical trial NCT03187795: Mirabegron and Oxybutynin Safety and Efficacy Trial in Spinal Cord Injury
Official title: Efficacy and Tolerability of Mirabegron Compared to Oxybutynin Chloride Immediate Release for Neurogenic Detrusor Overactivity in Persons With Chronic Spinal Cord Injury: A Randomized, Double-Blind, Controlled, Cross-Over Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Spinal Cord Injuries
Urinary Bladder, Neurogenic
Keywords: Spinal Cord Injuries
Randomized Controlled Trial
Neurogenic Bladder
Rehabilitation
Lead sponsor: Kessler Foundation
Sponsor class: OTHER
Collaborators: name: National Institute on Disability, Independent Living, and Rehabilitation Research
First posted: 2017-06-15
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: After a two-day washout period, participants will be randomly assigned to one of two treatment groups: 1) an escalating dose of mirabegron for 6 weeks (25 mg once daily plus two placebo pills for 2 weeks, followed by 50 mg once daily plus 2 placebo pills for 4 weeks); or 2) Oxybutynin IR (5 mg orally three times daily) for 6 weeks. All participants will then be switched to the opposite study treatment for 6 weeks. Assessments will be performed at Baseline, Week 6 (completion of first study medication and prior to administration of second study medication), and Week 12 (completion of second study medication).
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to determine the effectiveness and safety of mirabegron compared to oxybutynin chloride immediate release (oxybutynin IR) for a condition called neurogenic detrusor overactivity in individuals with chronic spinal cord injury (SCI).

Detailed description: Neurogenic detrusor overactivity or "NDO" is common in people with spinal cord injury (SCI) and is a medical condition characterized by involuntary urinary bladder contractions. These bladder contractions can cause episodes of urinary incontinence (involuntary urine leakage) and/or high bladder pressures that can lead to poor drainage from the kidneys and urinary tract infections (UTIs).

Neurogenic detrusor overactivity is most commonly treated with a medication called oxybutynin (Ditropan); however, this medication is associated with side effects such as dry mouth and constipation. Mirabegron (Myrbetriq) is a newer medication approved by the Food and Drug Administration for the treatment of overactive bladder that does not cause dry mouth or constipation; however, its use in persons with SCI is investigational.

The purpose of this research study is to determine the effectiveness and safety of mirabegron compared to oxybutynin chloride immediate release (oxybutynin IR) for neurogenic detrusor overactivity in individuals with SCI.

Eligibility criteria: Inclusion Criteria:

* The subject has a neurological impairment secondary to a traumatic spinal cord injury that occurred at least twelve (12) months prior to the screening visit.
* The injury is classified as complete or incomplete (AIS grade A-D) and the neurological level of the injury is above T12.
* The subject's method of bladder management is intermittent catheterization (IC) or indwelling catheter (transurethral or suprapubic).
* There is urodynamic documentation of neurogenic detrusor overactivity (NDO).
* The subject is on a stable dose of oxybutynin IR three times daily.
* The subject is able and willing to comply with the study protocol, including availability for all scheduled clinic visits and locomotor training sessions.
* The subject is able to and has voluntarily given informed consent prior to the performance of any study-specific procedures.

Exclusion Criteria:

* The subject has taken mirabegron within one month of the Screening Visit.
* The subject has received a botulinum toxin injection to the bladder within one year of the Screening Visit.
* The subject is allergic to mirabegron.
* The subject has a history of uncontrolled autonomic dysreflexia or significant autonomic dysreflexia on urodynamics (systolic BP≥150 mm/Hg).
* The subject has a known history of significant anatomical problems of the upper tracts, including hydronephrosis, kidney stones, or ureteropelvic junction obstruction.
* The subject has a known history or treatment for a non-neurogenic bladder or prostate problem (prostate cancer, bladder cancer).
* The subject has recurrent UTIs, defined as a UTI more than every three months.
* The subject has untreated Grade 3 or above vesicoureteral reflux.
* If female, the subject is pregnant (documented by a urine pregnancy test) or breastfeeding.
* The subject has taken another investigational drug within 30 days before screening.
* The subject has a medical condition that might pose a safety issue or would interfere with interpretation of study results or study conduct.

Primary outcomes:
measure: Change in cystometric bladder capacity during filing cystometry
timeFrame: Week 6 and Week 12
Secondary outcomes:
measure: Change in detrusor leak point pressure
timeFrame: Week 6 and Week 12
measure: Change in maximum detrusor pressure
timeFrame: Week 6 and Week 12
measure: Change in bladder compliance during filling cystometry
timeFrame: Week 6 and Week 12
measure: Change in post-void residual volume
timeFrame: Week 6 and Week 12
measure: Change on International Lower Urinary Tract Function Basic Spinal Cord Injury (SCI) Data Set
timeFrame: Week 6 and Week 12
measure: Change on Bowel Function Measures - International SCI Bowel Function Basic & Extended Data Sets
timeFrame: Week 6 and Week 12
measure: Change in California Verbal Learning Test - II (CVLT) scores
timeFrame: Week 6 and Week 12
measure: Change in Symbol Digit Modalities Test oral version (SDMT) scores
timeFrame: Week 6 and Week 12
measure: Wechsler Test of Adult Reading (WTAR) score
timeFrame: Screening Visit
measure: Change in Qualiveen scores
timeFrame: Week 6 and Week 12
measure: Change in SCI-QOL Bowel & Bladder Management Difficulties scores
timeFrame: Week 6 and Week 12
measure: Change in Subject Global Impression (SGI) of Change score
timeFrame: Week 6 and Week 12
measure: Change in Clinician Global Impression (CGI) of Change score
timeFrame: Week 6 and Week 12
Other outcomes:
measure: Adverse Event Case Report Form
timeFrame: Every two weeks for 12 weeks
measure: Side Effects Record
timeFrame: Every two weeks for 12 weeks
Locations:
city: West Orange
country: United States
facility: Kessler Institute for Rehabilitation
state: New Jersey
Study officials:
affiliation: Kessler Institute for Rehabilitation
name: Todd A. Linsenmeyer, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Kessler Institute for Rehabilitation
name: Steven C. Kirshblum, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Kessler Foundation
name: Trevor A. Dyson-Hudson, M.D.
role: PRINCIPAL_INVESTIGATOR
References: