Back to resultsMirabegron and Oxybutynin Safety and Efficacy Trial in Spinal Cord Injury (MOSET-SCI)
Primary Purpose
Spinal Cord Injuries, Urinary Bladder, Neurogenic
Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Oxybutynin Chloride IR
Mirabegron
Sponsored by
About this trial
This is an interventional treatment trial for Spinal Cord Injuries focused on measuring Spinal Cord Injuries, Randomized Controlled Trial, Neurogenic Bladder, Rehabilitation
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.
Sites / Locations
- Kessler Institute for RehabilitationRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Oxybutynin chloride IR then Mirabegron
Mirabegron then Oxybutynin chloride IR
Arm Description
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).
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
Outcomes
Primary Outcome Measures
Change in cystometric bladder capacity during filing cystometry
The cystometric bladder capacity is the bladder volume (ml) at the end of the filling cystometrogram, when 'permission to void' is usually given.
Secondary Outcome Measures
Change in detrusor leak point pressure
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
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
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
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
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
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
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 Symbol Digit Modalities Test oral version (SDMT) scores
Processing speed will be assessed by the Symbol Digit Modalities Test oral version.
Wechsler Test of Adult Reading (WTAR) score
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
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
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.
Change in Subject Global Impression (SGI) of Change score
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
The study physician will rate on a 7-point scale the subject's overall clinical condition following treatment as compared to that at baseline.
Full Information
NCT ID
NCT03187795
First Posted
June 12, 2017
Last Updated
December 14, 2019
Sponsor
Kessler Foundation
Collaborators
National Institute on Disability, Independent Living, and Rehabilitation Research
1. Study Identification
Unique Protocol Identification Number
NCT03187795
Brief Title
Mirabegron and Oxybutynin Safety and Efficacy Trial in Spinal Cord Injury
Acronym
MOSET-SCI
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
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Unknown status
Study Start Date
April 3, 2019 (Actual)
Primary Completion Date
September 30, 2021 (Anticipated)
Study Completion Date
March 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Kessler Foundation
Collaborators
National Institute on Disability, Independent Living, and Rehabilitation Research
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injuries, Urinary Bladder, Neurogenic
Keywords
Spinal Cord Injuries, Randomized Controlled Trial, Neurogenic Bladder, Rehabilitation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
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).
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
62 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Oxybutynin chloride IR then Mirabegron
Arm Type
Experimental
Arm Description
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).
Arm Title
Mirabegron then Oxybutynin chloride IR
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Oxybutynin Chloride IR
Other Intervention Name(s)
Ditropan
Intervention Description
Oxybutynin chloride immediate release (IR) 5 mg three times daily for 6 weeks
Intervention Type
Drug
Intervention Name(s)
Mirabegron
Other Intervention Name(s)
Myrbetriq
Intervention Description
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).
Primary Outcome Measure Information:
Title
Change in cystometric bladder capacity during filing cystometry
Description
The cystometric bladder capacity is the bladder volume (ml) at the end of the filling cystometrogram, when 'permission to void' is usually given.
Time Frame
Week 6 and Week 12
Secondary Outcome Measure Information:
Title
Change in detrusor leak point pressure
Description
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.
Time Frame
Week 6 and Week 12
Title
Change in maximum detrusor pressure
Description
Maximum detrusor pressure (ml/cm H2O) as the name implies, is the maximum detrusor pressure during filling cystometry.
Time Frame
Week 6 and Week 12
Title
Change in bladder compliance during filling cystometry
Description
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).
Time Frame
Week 6 and Week 12
Title
Change in post-void residual volume
Description
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.
Time Frame
Week 6 and Week 12
Title
Change on International Lower Urinary Tract Function Basic Spinal Cord Injury (SCI) Data Set
Description
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.
Time Frame
Week 6 and Week 12
Title
Change on Bowel Function Measures - International SCI Bowel Function Basic & Extended Data Sets
Description
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.
Time Frame
Week 6 and Week 12
Title
Change in California Verbal Learning Test - II (CVLT) scores
Description
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.
Time Frame
Week 6 and Week 12
Title
Change in Symbol Digit Modalities Test oral version (SDMT) scores
Description
Processing speed will be assessed by the Symbol Digit Modalities Test oral version.
Time Frame
Week 6 and Week 12
Title
Wechsler Test of Adult Reading (WTAR) score
Description
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.
Time Frame
Screening Visit
Title
Change in Qualiveen scores
Description
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.
Time Frame
Week 6 and Week 12
Title
Change in SCI-QOL Bowel & Bladder Management Difficulties scores
Description
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.
Time Frame
Week 6 and Week 12
Title
Change in Subject Global Impression (SGI) of Change score
Description
The SGI of change is a subject-rated instrument that measures change in the subject's overall status on a 7-point scale.
Time Frame
Week 6 and Week 12
Title
Change in Clinician Global Impression (CGI) of Change score
Description
The study physician will rate on a 7-point scale the subject's overall clinical condition following treatment as compared to that at baseline.
Time Frame
Week 6 and Week 12
Other Pre-specified Outcome Measures:
Title
Adverse Event Case Report Form
Description
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.
Time Frame
Every two weeks for 12 weeks
Title
Side Effects Record
Description
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.
Time Frame
Every two weeks for 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Todd A. Linsenmeyer, M.D.
Phone
973-243-6924
Email
tlinsenmeyer@kessler-rehab.com
First Name & Middle Initial & Last Name or Official Title & Degree
Trevor A. Dyson-Hudson, M.D.
Phone
973-324-3576
Email
tdysonhudson@kesslerfoundation.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Todd A. Linsenmeyer, M.D.
Organizational Affiliation
Kessler Institute for Rehabilitation
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Steven C. Kirshblum, M.D.
Organizational Affiliation
Kessler Institute for Rehabilitation
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Trevor A. Dyson-Hudson, M.D.
Organizational Affiliation
Kessler Foundation
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kessler Institute for Rehabilitation
City
West Orange
State/Province
New Jersey
ZIP/Postal Code
07052
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Todd A. Linsenmeyer, M.D.
Phone
973-243-6924
Email
tlinsenmeyer@kessler-rehab.com
First Name & Middle Initial & Last Name & Degree
Trevor A. Dyson-Hudson, M.D.
Phone
973-324-3576
Email
tdysonhudson@kesslerfoundation.org
First Name & Middle Initial & Last Name & Degree
Todd A. Linsenmeyer, M.D.
First Name & Middle Initial & Last Name & Degree
Steven C. Kirshblum, M.D.
First Name & Middle Initial & Last Name & Degree
Trevor A. Dyson-Hudson, M.D.
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Mirabegron and Oxybutynin Safety and Efficacy Trial in Spinal Cord Injury
We'll reach out to this number within 24 hrs