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
Overview
- Phase
- Phase 2
- Intervention
- Oxybutynin Chloride IR
- Conditions
- Spinal Cord Injuries
- Sponsor
- Kessler Foundation
- Enrollment
- 62
- Locations
- 1
- Primary Endpoint
- Change in cystometric bladder capacity during filing cystometry
- Last Updated
- 6 years ago
Overview
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.
Investigators
Trevor Dyson-Hudson, M.D.
Director, Spinal Cord Injury Research
Kessler Foundation
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 T
- •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.
Arms & Interventions
Oxybutynin chloride IR then Mirabegron
Subjects randomized to this group will receive oxybutynin IR (5 mg three times daily) for 6 weeks. After the initial 6 weeks, subjects in this group will then be switched to an escalating dose of mirabegron for 6 weeks (25 mg once daily for 2 weeks, followed by 50 mg once daily for 4 weeks; Note: two placebo daily will be included with mirabegron once daily to match the frequency of dosing to oxybutynin IR three times daily).
Intervention: Oxybutynin Chloride IR
Oxybutynin chloride IR then Mirabegron
Subjects randomized to this group will receive oxybutynin IR (5 mg three times daily) for 6 weeks. After the initial 6 weeks, subjects in this group will then be switched to an escalating dose of mirabegron for 6 weeks (25 mg once daily for 2 weeks, followed by 50 mg once daily for 4 weeks; Note: two placebo daily will be included with mirabegron once daily to match the frequency of dosing to oxybutynin IR three times daily).
Intervention: Mirabegron
Mirabegron then Oxybutynin chloride IR
Subjects randomized to this group will receive an escalating dose of mirabegron for 6 weeks (25 mg once daily for 2 weeks, followed by 50 mg once daily for 4 weeks; Note: two placebo daily will be included with mirabegron once daily to match the frequency of dosing to oxybutynin IR three times daily). After the initial 6 weeks, subjects in this group will then be switched to receive oxybutynin IR (5 mg three times daily) for 6 weeks
Intervention: Oxybutynin Chloride IR
Mirabegron then Oxybutynin chloride IR
Subjects randomized to this group will receive an escalating dose of mirabegron for 6 weeks (25 mg once daily for 2 weeks, followed by 50 mg once daily for 4 weeks; Note: two placebo daily will be included with mirabegron once daily to match the frequency of dosing to oxybutynin IR three times daily). After the initial 6 weeks, subjects in this group will then be switched to receive oxybutynin IR (5 mg three times daily) for 6 weeks
Intervention: Mirabegron
Outcomes
Primary Outcomes
Change in cystometric bladder capacity during filing cystometry
Time Frame: Week 6 and Week 12
The cystometric bladder capacity is the bladder volume (ml) at the end of the filling cystometrogram, when 'permission to void' is usually given.
Secondary Outcomes
- Change in detrusor leak point pressure(Week 6 and Week 12)
- Change in maximum detrusor pressure(Week 6 and Week 12)
- Change in bladder compliance during filling cystometry(Week 6 and Week 12)
- Change in post-void residual volume(Week 6 and Week 12)
- Change on International Lower Urinary Tract Function Basic Spinal Cord Injury (SCI) Data Set(Week 6 and Week 12)
- Change on Bowel Function Measures - International SCI Bowel Function Basic & Extended Data Sets(Week 6 and Week 12)
- Change in California Verbal Learning Test - II (CVLT) scores(Week 6 and Week 12)
- Change in Symbol Digit Modalities Test oral version (SDMT) scores(Week 6 and Week 12)
- Wechsler Test of Adult Reading (WTAR) score(Screening Visit)
- Change in Qualiveen scores(Week 6 and Week 12)
- Change in SCI-QOL Bowel & Bladder Management Difficulties scores(Week 6 and Week 12)
- Change in Subject Global Impression (SGI) of Change score(Week 6 and Week 12)
- Change in Clinician Global Impression (CGI) of Change score(Week 6 and Week 12)