Biomarker Predictors of Memantine Sensitivity in Patients With Alzheimer's Disease

Study Overview
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Brief Summary
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The effects of the medication, memantine, on brain functions and the symptoms of Alzheimer's Disease will be tested

Official Title
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Biomarker Predictors of Memantine Sensitivity in Patients With Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: Memantine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion: Alzheimer's Disease Research Center-confirmed diagnosis of AD Mini-Mental State Examination (MMSE) score 10-22 OR a Montreal Cognitive Assessment (MOCA) score of 15-24 Age 50-83 y Knowledgeable caregiver Ambulatory Medically stable; Audiometric testing (detection < 40 db(A) at 1000 Hz) Informed consent Exclusion: Active systemic illness (e.g. heart disease, liver failure, renal insufficiency, cancer, HIV, tuberculosis, Hepatitis C) Current psychiatric or neurologic illness other than AD History of vascular disease, myocardial infarction, cerebrovascular accidents, transient ischemic attack, seizure, head injury with loss of consciousness; substance dependence (including alcohol and Opioid) Past treatment with memantine; unable to tolerate acetylcholinesterase inhibitor Investigational drug treatment < 30 d of screening Current meds: amantadine, riluzole, other pro-cognitive medication, opioids Positive urine toxicology for non-prescribed psychoactive substance Actively enrolled in cognitive remediation therapy

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 83 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Memantine<br> | Drug: Memantine<br>* Phase 1 will test the acute effects of memantine (20 mg po) vs. placebo (PBO) on early auditory information processing measures in 32 carefully characterized patients with mild-to-moderate severity AD who are not currently taking AD medications. From this challenge test, a set of early auditory information processing memantine sensitivity measures will be derived for each patient. In Phase 2, all patients will begin an open-label trial of memantine monotherapy, titrated to 10 mg bid, with outcome measures collected after 8, 16 and 24 weeks of treatment. Medication adjustments are not restricted, and response heterogeneity is anticipated.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Phase 1 will test the acute effects of memantine (20 mg po) vs. placebo (PBO) on early auditory information processing measures in 32 carefully characterized patients with mild-to-moderate severity AD who are not currently taking AD medications. From this challenge test, a set of Early auditory information processing P memantine sensitivity measures will be derived for each patient. In Phase 2, all patients will begin an open-label trial of memantine monotherapy, titrated to 10 mg bid, with outcome measures collected after 8, 16 and 24 weeks of treatment. Medication adjustments are not restricted, and response heterogeneity is anticipated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline measure in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) at 8, 16 and 24 weeks | measures cognitive ability | 0, 8, 16, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline measure in Neuropsychiatric Inventory-Questionnaire (NPI-Q) at 8, 16 and 24 weeks | measures behavioral symptoms | 0, 8, 16, 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease, Alzheimer Disease, Alzheimer, AD, Alzheimer's