Clinical trial NCT03612401: Treatment of Spinal Cord Injury Patients for Neurogenic Bladder: Anticholinergic Agent vs. Mirabegron
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Spinal Cord Injuries
Neurogenic Bladder
Cognitive Change
Keywords: Spinal cord injury
SCI
Neurogenic bladder
Overactive bladder
anticholinergic
mirabegron
cognitive
cognition
NGB
OAB
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
First posted: 2018-08-02
Enrollment: 20
Sex: ALL
Minimum age (years): 60
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label, pilot study comparing baseline measurement anticholinergic agent vs. study intervention mirabegron (MYRBETRIC ®) to evaluate cognitive impact and efficacy (SCIMYR)
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Change in cognitive measure - Logical Memory I (Immediate) - baseline and post treatment with mirabegron
timeFrame: Change from Week 0 to Week 26
Secondary outcomes:
measure: Change in cognitive measure of memory (SLUMS) - baseline and post treatment with mirabegron
timeFrame: Change from Week 0 to Week 26
measure: Change in cognitive measure of executive function (Stroop test) - baseline and post treatment with mirabegron
timeFrame: Change from Week 0 to Week 26
measure: Change in cognitive measure of executive function (SDMT) - baseline and post treatment with mirabegron
timeFrame: Change from Week 0 to Week 26
measure: Change in memory and executive function (TEXAS) - baseline and post treatment with mirabegron
timeFrame: Change from Week 0 to Week 26
measure: Change in Neurogenic Bladder Symptom Score (NBSS) - baseline and post treatment with mirabegron
timeFrame: Change from Week 0 to Week 26
measure: Change in Neurogenic Bowel Dysfunction Score (NBD) - baseline and post treatment with mirabegron
timeFrame: Change from Week 0 to Week 26
measure: Change in cognitive measure - Logical Memory II (Delayed) - baseline and post treatment with mirabegron
timeFrame: Change from Week 0 to Week 26
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: South Texas Veterans Health Care System, Audie L. Murphy Hospital
state: Texas
Study officials:
affiliation: UT Health San Antonio and VA Spinal Cord Clinic
name: Michelle Trbovich, MD
role: PRINCIPAL_INVESTIGATOR
References: