Sanctura Muscarinic Receptor Antagonist Resists Transport (SMART) Trial

Study Overview
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Brief Summary
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This study evaluates the penetration through the blood-brain-barrier of trospium chloride at plasma steady state (Day 10) in elderly subjects with overactive bladder symptoms. Trospium levels in cerebrospinal fluid (CSF) and peak and trough plasma levels will be measured. Baseline and day 10 post-dose neurocognitive testing will be compared using a reliable change index to assess if any study subject shows evidence of a clinically and statistically significant change in memory.

Conditions
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Pharmacokinetics, Elderly, Overactive Bladder

Intervention / Treatment
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* Drug: Trospium Chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 65-75 years of age without evidence of memory impairment Subject has overactive bladder symptoms but otherwise healthy Non-smoker (refrained from any tobacco usage, including smokeless tobacco, nicotine patches, etc., for 6 months prior to the screening visit) Weight within normal range Ability to follow study instructions and likely to complete all required visits Exclusion Criteria: Residual urine within bladder greater than 4 ounces Moderate or severe memory impairment Bleeding disorder Blood-thinning agents Concurrent overactive bladder medication Concurrent dementia drugs: Aricept (donepezil), Namenda (memantine), Cognex (tacrine), Exelon (rivastigmine), Razadyne (galantamine), galantamine or similar drugs for dementia Chronic kidney failure Abdominal bypass surgery for obesity

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 75 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trospium Chloride Extended Release, 60 mg<br>Trospium Chloride Extended Release, 60 mg | Drug: Trospium Chloride<br>* Extended release, 60 mg, oral daily<br>* Other names: Sanctura XR™ 60 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral Spinal Fluid Levels of Trospium at Day 10, Hour 5 | Cerebral spinal fluid levels of Trospium at day 10, hour 5. Cerebral spinal fluid was collected from each patient. | Day 10, Hour 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Study Subjects With No Clinically Significant Effect on Neurocognitive Function Total Recall Score as Measured by the Hopkins Verbal Learning Test-Revised (HVLT-R) at Day 10 Post-Dose | The HVLT-R is an instrument used to measure verbal learning and memory (recognition and recall). It consists of 3 learning trials: free recall, delayed recall, and yes/no delayed recognition. The total recall score was the sum of 3 'free recall' learning trials, and reflects the patient's ability to learn. The total score ranges from 0 (no memory) to 36 (best memory). | Day 10 | 
| Percentage of Study Subjects With No Clinically Significant Effect on Neurocognitive Function Delayed Recall Score as Measured by the Hopkins Verbal Learning Test-Revised (HVLT-R) at Day 10 Post-Dose | The HVLT-R is an instrument used to measure verbal learning and memory (recognition and recall). It consists of 3 learning trials: free recall, delayed recall, and yes/no delayed recognition trial. The delayed recall score provides a measure of the patient's recent memory. The total score ranges from 0 (no memory) to 12 (best memory). | Day 10 | 
| Percentage of Study Subjects With No Clinically Significant Effect on Neurocognitive Function as Measured by the Brief Visuospatial Memory Test-Revised (BVMT-R) Total Score at Day 10 Post-Dose | The BVMT-R is an instrument used to measure visual learning and memory (recognition and recall). It consists of 3 learning trials: free recall, delayed recall, and yes/no delayed recognition trial. The total recall score is the sum of 3 free recall learning trials, and reflects the patient's ability to learn. The total score ranges from 0 (no memory) to 12 (best memory). Due to technical problems associated with the administration of the test, the results were invalid. | Day 10 | 
| Percentage of Study Subjects With No Clinically Significant Effect on Neurocognitive Function as Measured by the Brief Visuospatial Memory Test-Revised (BVMT-R) Delayed Recall Score at Day 10 Post-Dose | The BVMT-R is an instrument used to measure visual learning and memory (recognition and recall). It consists of 3 learning trials: free recall, delayed recall, and a yes/no delayed recognition trial. The delayed recall score, derived from the delayed recall trial, provides a measure of the patient's recent memory. The total score ranges from 0 (no memory) to 12 (best memory). Due to technical problems associated with the administration of the test, the results were invalid. | Day 10 |