Spinal Cord Injuries, Urinary Bladder, Neurogenic
Conditions
Keywords
Spinal Cord Injuries, Randomized Controlled Trial, Neurogenic Bladder, Rehabilitation
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.
Interventions
DRUGOxybutynin Chloride IR
Oxybutynin chloride immediate release (IR) 5 mg three times daily for 6 weeks
DRUGMirabegron
Mirabegron 25 mg tablet once daily for 2 weeks, followed by mirabegron 50 mg once daily for 4 weeks (Note: Placebo twice daily will be included with mirabegron once daily to match the three-time daily dosing of oxybutynin IR in the other intervention).
Sponsors
National Institute on Disability, Independent Living, and Rehabilitation Research
Kessler Foundation
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All study investigators, participants, and assessors will be blind to group assignment. Blinding code will only be broken in emergency situations for reasons of subject safety, where knowledge of the treatment administered is necessary for the treatment of the adverse event under Good Clinical Practices (GCPs), or when required by local regulatory authorities.
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in cystometric bladder capacity during filing cystometry | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in detrusor leak point pressure | Week 6 and Week 12 | The detrusor leak point pressure (cm H2O) is defined as the lowest detrusor pressure at which urine leakage occurs in the absence of either a detrusor contraction or increased abdominal pressure. |
| Change in maximum detrusor pressure | Week 6 and Week 12 | Maximum detrusor pressure (ml/cm H2O) as the name implies, is the maximum detrusor pressure during filling cystometry. |
| Change in bladder compliance during filling cystometry | Week 6 and Week 12 | Bladder compliance during filling cystometry (ml/cm H2O) is the relationship between change in bladder volume and change in detrusor pressure and is calculated by dividing the volume change (ΔV) by the change in detrusor pressure (Δρdet) during that change in bladder volume (C= ΔV/Δρdet). |
| Change in post-void residual volume | Week 6 and Week 12 | The post-void residual volume (ml) is defined as the volume of urine left in the bladder at the end of micturition1 and is recommended as a core urodynamic outcome measure in SCI. |
| Change on International Lower Urinary Tract Function Basic Spinal Cord Injury (SCI) Data Set | Week 6 and Week 12 | The purpose of the Lower Urinary Tract Function Basic Data Set for Spinal Cord Injury (SCI) individuals is to standardize the collection and reporting of information on the lower urinary tract and to make it possible to evaluate and compare results from various published studies. |
| Change on Bowel Function Measures - International SCI Bowel Function Basic & Extended Data Sets | Week 6 and Week 12 | The International Bowel Function Basic and Extended SCI Data Sets present a standardized format for the collection and reporting of an extended amount of information on bowel function in persons with SCI. |
| Change in California Verbal Learning Test - II (CVLT) scores | Week 6 and Week 12 | Memory will be assessed by the California Verbal Learning Test - II (CVLT). It consists of a list of 16 words from 4 semantic categories presented orally over 5 trials and includes a 20 minute delayed recall trial as well as a recognition trial. |
| Change in Subject Global Impression (SGI) of Change score | Week 6 and Week 12 | The SGI of change is a subject-rated instrument that measures change in the subject's overall status on a 7-point scale. |
| Change in Clinician Global Impression (CGI) of Change score | Week 6 and Week 12 | The study physician will rate on a 7-point scale the subject's overall clinical condition following treatment as compared to that at baseline. |
| Change in Symbol Digit Modalities Test oral version (SDMT) scores | Week 6 and Week 12 | Processing speed will be assessed by the Symbol Digit Modalities Test oral version. |
| Wechsler Test of Adult Reading (WTAR) score | Screening Visit | The Wechsler Test of Adult Reading will be administered to provide an estimate of verbal intelligence for later use as a covariate in the analyses of the cognitive outcomes. The WTAR is composed of 50 irregularly spelled words and takes approximately 10 minutes to complete. |
| Change in Qualiveen scores | Week 6 and Week 12 | The Qualiveen was developed as a condition-specific QOL measure for individuals with SCI. It consists of 30 items focusing on four aspects of individuals' lives related to their urinary problems: bother with limitations, frequency of limitations, fears, and feelings. |
| Change in SCI-QOL Bowel & Bladder Management Difficulties scores | Week 6 and Week 12 | The SCI-QOL Bladder Management Difficulties and SCI-QOL Bowel Management Difficulties were developed as QOL measure for individuals with SCI and are part of the SCI-QOL measurement system. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event Case Report Form | Every two weeks for 12 weeks | Adverse experience(s) will be recorded on the Adverse Event Case Report Form, including the date and time of onset, severity, the relationship to study intervention, the date of resolution, the action taken, and the outcome of the adverse experience. The responsible physician will make a causality assessment for every adverse experience. |
| Side Effects Record | Every two weeks for 12 weeks | Participants will be provided a list of side-effects associated with oxybutynin and mirabegron treatment. Three lines marked other for open-choice responses will accompany the selection of options for forced-choice side-effects. Participants will rate the severity (visual analog scale (VAS); 0-100) and frequency (never, occasionally, sometimes, often or always) of side effects for each of the forced and open choice answers. Severity and frequency of side-effects will be rated by participants every 2 weeks during the intervention part of the study. |
Countries
United States
Contacts
Primary ContactTodd A. Linsenmeyer, M.D.
Backup ContactTrevor A. Dyson-Hudson, M.D.
Outcome results
None listed