Cognitive Change, Neurogenic Bladder, Spinal Cord Injuries
Conditions
Keywords
Spinal cord injury, SCI, Neurogenic bladder, Overactive bladder, anticholinergic, mirabegron, cognitive, cognition, NGB, OAB
Brief summary
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
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).
Interventions
DRUGMirabegron
Beta-3 adenoreceptor agonist
Sponsors
The University of Texas Health Science Center at San Antonio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label, pilot study comparing baseline measurement anticholinergic agent vs. study intervention mirabegron (MYRBETRIC ®) to evaluate cognitive impact and efficacy (SCIMYR)
Eligibility
Sex/Gender
ALL
Age
60 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Both genders with spinal cord injury being treated for neurogenic bladder and age \>60 years 2. All ethnic groups 3. Veterans will be enrolled to allow mailing of study medication by VA pharmacies. 4. 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) 5. Taking a minimum regimen for 3 months of anticholinergic agent.
Exclusion criteria
1. Diagnosis of dementia or cognitive impairment from another condition such as TBI (traumatic brain injury), ALZ (alzheimers), Lewy body dementia or vascular dementia 2. End stage renal disease (GFR \<30) or bladder obstruction 3. Poorly controlled blood pressure (BP), systolic BP\>180, diastolic BP\>110 mmHg) 4. Renal function - exclude if serum creatinine \>2x normal range 5. Liver function - exclude if \>2x normal liver enzyme levels 6. 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) 7. Current treatment with desipramine, digoxin 8. 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). 9. Subject is considered unsuitable for the study in the opinion of the investigator for any other reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in cognitive measure - Logical Memory I (Immediate) - baseline and post treatment with mirabegron | Change from Week 0 to Week 26 | Wechsler Memory Scale, 4th edition (WMS-IV) subtest |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in cognitive measure of executive function (Stroop test) - baseline and post treatment with mirabegron | Change from Week 0 to Week 26 | Stroop Color and Word Test - a series of color-word and picture-word tests of executive function |
| Change in cognitive measure of executive function (SDMT) - baseline and post treatment with mirabegron | Change from Week 0 to Week 26 | Symbol Digit Modalities Test - a series of symbols to assess executive function |
| Change in memory and executive function (TEXAS) - baseline and post treatment with mirabegron | Change from Week 0 to Week 26 | Texas Executive Assessment (TEXAS) - A series of short term recall measures |
| Change in cognitive measure of memory (SLUMS) - baseline and post treatment with mirabegron | Change from Week 0 to Week 26 | Saint Louis University Mental Status Exam (SLUMS) - a series of shapes and recall measures |
| Change in Neurogenic Bowel Dysfunction Score (NBD) - baseline and post treatment with mirabegron | Change from Week 0 to Week 26 | Neurogenic bowel questionnaire |
| Change in cognitive measure - Logical Memory II (Delayed) - baseline and post treatment with mirabegron | Change from Week 0 to Week 26 | Wechsler Memory Scale, 4th edition (WMS-IV) subtest |
| Change in Neurogenic Bladder Symptom Score (NBSS) - baseline and post treatment with mirabegron | Change from Week 0 to Week 26 | Neurogenic bladder symptom questionnaire |
Countries
United States
Outcome results
None listed