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

Early Phase 1

Completed

• Conditions: Cognitive Change; Spinal Cord Injuries; Neurogenic Bladder
• Interventions: Drug: Mirabegron

• Registration Number: NCT03612401
• Lead Sponsor: The University of Texas Health Science Center at San Antonio

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).

Study Timeline

• Study First Submitted: 2018-07-09
• Study First Submitted QC: 2018-07-26
• Study First Posted: 2018-08-02
• Study Start: 2018-12-05
• Primary Completion: 2020-03-23
• Study Completion: 2021-03-31
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-15
• Last Update Posted: 2021-06-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neurogenic Bladder	Mirabegron	Spinal Cord Injury patients with known neurogenic bladder on treatment with Anticholinergic Agents at baseline switched to mirabegron as the study intervention

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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 Neurogenic Bladder Symptom Score (NBSS) - baseline and post treatment with mirabegron	Change from Week 0 to Week 26	Neurogenic bladder symptom questionnaire
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 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 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 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

Trial Locations

Locations (1)

South Texas Veterans Health Care System, Audie L. Murphy Hospital; 🇺🇸 San Antonio, Texas, United States