Mirabegron and Oxybutynin Safety and Efficacy Trial in Spinal Cord Injury (MOSET-SCI)

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

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).

Study Overview

• Status: Unknown
• Conditions: Spinal Cord Injuries; Urinary Bladder, Neurogenic
• Intervention / Treatment: Drug: Oxybutynin Chloride IR; Drug: Mirabegron

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.

• Study Type: Interventional
• Enrollment (Anticipated): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • West Orange, New Jersey, United States, 07052
      • Recruiting
      • Kessler Institute for Rehabilitation
      • Contact: Trevor A. Dyson-Hudson, M.D.; Phone Number: 973-324-3576; Email: tdysonhudson@kesslerfoundation.org
      • Principal Investigator: Steven C. Kirshblum, M.D.
      • Contact: Todd A. Linsenmeyer, M.D.; Phone Number: 973-243-6924; Email: tlinsenmeyer@kessler-rehab.com
      • Principal Investigator: Todd A. Linsenmeyer, M.D.
      • Principal Investigator: Trevor A. Dyson-Hudson, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: Oxybutynin Chloride IR; Oxybutynin chloride immediate release (IR) 5 mg three times daily for 6 weeks; Other Names: Ditropan; Drug: Mirabegron; 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).; Other Names: Myrbetriq
Experimental: 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	Drug: Oxybutynin Chloride IR; Oxybutynin chloride immediate release (IR) 5 mg three times daily for 6 weeks; Other Names: Ditropan; Drug: Mirabegron; 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).; Other Names: Myrbetriq

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 6 and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 6 and Week 12
Change in maximum detrusor pressure	Maximum detrusor pressure (ml/cm H2O) as the name implies, is the maximum detrusor pressure during filling cystometry.	Week 6 and Week 12
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).	Week 6 and Week 12
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.	Week 6 and Week 12
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.	Week 6 and Week 12
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.	Week 6 and Week 12
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.	Week 6 and Week 12
Change in Symbol Digit Modalities Test oral version (SDMT) scores	Processing speed will be assessed by the Symbol Digit Modalities Test oral version.	Week 6 and Week 12
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.	Screening Visit
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.	Week 6 and Week 12
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.	Week 6 and Week 12
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.	Week 6 and Week 12
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.	Week 6 and Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event Case Report Form	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.	Every two weeks for 12 weeks
Side Effects Record	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.	Every two weeks for 12 weeks

Collaborators and Investigators

• Sponsor: Kessler Foundation
• Collaborators: National Institute on Disability, Independent Living, and Rehabilitation Research
• Investigators: Principal Investigator: Steven C. Kirshblum, M.D., Kessler Institute for Rehabilitation; Principal Investigator: Trevor A. Dyson-Hudson, M.D., Kessler Foundation; Principal Investigator: Todd A. Linsenmeyer, M.D., Kessler Institute for Rehabilitation

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2019
• Primary Completion (Anticipated): September 30, 2021
• Study Completion (Anticipated): March 30, 2022

Study Registration Dates

• First Submitted: June 12, 2017
• First Submitted That Met QC Criteria: June 13, 2017
• First Posted (Actual): June 15, 2017

Study Record Updates

• Last Update Posted (Actual): December 17, 2019
• Last Update Submitted That Met QC Criteria: December 14, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Rehabilitation; Randomized Controlled Trial; Neurogenic Bladder; Spinal Cord Injuries
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Neurologic Manifestations; Trauma, Nervous System; Spinal Cord Diseases; Wounds and Injuries; Spinal Cord Injuries; Urinary Bladder, Neurogenic; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Oxybutynin; Mirabegron
• Other Study ID Numbers: D-961-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• 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