Treatment of Spinal Cord Injury Patients for Neurogenic Bladder: Anticholinergic Agent vs. Mirabegron

Study Overview
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Brief Summary
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We propose to test the hypothesis that cognition will improve with substitution of mirabegron for the anticholinergic agent (AC) in elderly persons with spinal cord injury (SCI) who require neurogenic bladder (NGB) treatment.

Detailed Description
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The strong evidence for detrimental effects of AC agents on cognition, led the American Urological Association to update its guidelines in 2015 to include mirabegron as an alternative first-line agent for treatment of overactive bladder (OAB). NGB symptoms are very similar to OAB so the conditions are often treated similarly; however, data is lacking on the use of this promising agent for NGB. We thus propose to test the hypothesis that cognition will improve with substitution of mirabegron for the AC agent in elderly persons with SCI who require NGB treatment. Subjects eligible for enrollment will have been treated with an anticholinergic agent for at least 3 months prior to enrollment. Baseline measurements will be recorded for subjects currently treated with an AC agent, after enrollment, the subject will start treatment with the study drug. Measurements from baseline (AC agent) will be compared to measurements taken after study intervention (mirabegron).

Official Title
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Treatment of Spinal Cord Injury Patients for Neurogenic Bladder: an Open Label Pilot Study of Anticholinergic Agent vs. Mirabegron (MYRBETRIQ ®) to Evaluate Cognitive Impact and Efficacy

Conditions
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Neurogenic Bladder, Spinal Cord Injuries, Cognitive Change

Intervention / Treatment
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* Drug: Mirabegron


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both genders with spinal cord injury being treated for neurogenic bladder and age >60 years All ethnic groups Veterans will be enrolled to allow mailing of study medication by VA pharmacies. Laboratory results: Normal clinical labs for CBC (complete blood count), CMP (comprehensive metabolic panel), and UA (urinalysis) within past 6 months or repeat at screening if none. For example: HCT (hematocrit) ≥34%, GFR (glomerular filtration rate) ≥ 30 mL/min, liver enzymes (AST (aspartate aminotransferase test) < 2 x upper limit of normal, ALT (alanine aminotransferase test) < 2 x upper limit of normal, alkaline phosphatase < 2 X upper limit of normal), normal electrolytes, urinalysis and asymptomatic for UTI (urinary tract infection) Taking a minimum regimen for 3 months of anticholinergic agent. Exclusion Criteria: Diagnosis of dementia or cognitive impairment from another condition such as TBI (traumatic brain injury), ALZ (alzheimers), Lewy body dementia or vascular dementia End stage renal disease (GFR <30) or bladder obstruction Poorly controlled blood pressure (BP), systolic BP>180, diastolic BP>110 mmHg) Renal function - exclude if serum creatinine >2x normal range Liver function - exclude if >2x normal liver enzyme levels History of, or currently active treatment for cardiac dysrhythmias, including atrial fibrillation (eg. apixaban. If subject is currently taking metoprolol they will be monitored and dose may need to be adjusted on mirabegron) Current treatment with desipramine, digoxin Active/unstable conditions: inflammatory, thyroid, autoimmune, gastrointestinal (GI), hematologic, or neoplastic disorders. Exclude subjects with clinical lab values outside the normal range (other than as specified above). Subject is considered unsuitable for the study in the opinion of the investigator for any other reason

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label, pilot study comparing baseline measurement anticholinergic agent vs. study intervention mirabegron (MYRBETRIC ®) to evaluate cognitive impact and efficacy (SCIMYR)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Neurogenic Bladder<br>Spinal Cord Injury patients with known neurogenic bladder on treatment with Anticholinergic Agents at baseline switched to mirabegron as the study intervention | Drug: Mirabegron<br>* Beta-3 adenoreceptor agonist<br>* Other names: MYRBETRIQ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive measure - Logical Memory I (Immediate) - baseline and post treatment with mirabegron | Wechsler Memory Scale, 4th edition (WMS-IV) subtest | Change from Week 0 to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive measure of memory (SLUMS) - baseline and post treatment with mirabegron | Saint Louis University Mental Status Exam (SLUMS) - a series of shapes and recall measures | Change from Week 0 to Week 26 | 
| Change in cognitive measure of executive function (Stroop test) - baseline and post treatment with mirabegron | Stroop Color and Word Test - a series of color-word and picture-word tests of executive function | Change from Week 0 to Week 26 | 
| Change in cognitive measure of executive function (SDMT) - baseline and post treatment with mirabegron | Symbol Digit Modalities Test - a series of symbols to assess executive function | Change from Week 0 to Week 26 | 
| Change in memory and executive function (TEXAS) - baseline and post treatment with mirabegron | Texas Executive Assessment (TEXAS) - A series of short term recall measures | Change from Week 0 to Week 26 | 
| Change in Neurogenic Bladder Symptom Score (NBSS) - baseline and post treatment with mirabegron | Neurogenic bladder symptom questionnaire | Change from Week 0 to Week 26 | 
| Change in Neurogenic Bowel Dysfunction Score (NBD) - baseline and post treatment with mirabegron | Neurogenic bowel questionnaire | Change from Week 0 to Week 26 | 
| Change in cognitive measure - Logical Memory II (Delayed) - baseline and post treatment with mirabegron | Wechsler Memory Scale, 4th edition (WMS-IV) subtest | Change from Week 0 to Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCI, Spinal cord injury, Neurogenic bladder, Overactive bladder, anticholinergic, mirabegron, cognitive, cognition, NGB, OAB