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

NCT ID: NCT03703856

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-31
• Study Completion Date: 2025-12-30

Brief Summary

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

Detailed Description

Memantine (MEM) is an FDA-approved treatment for Alzheimer's Disease (AD), but its clinical effects vary from person-to-person. We have reported that a "test dose" of MEM significantly enhances early auditory information processing (EAIP) indices of brain function in both healthy adults and psychiatric patients, suggesting that these EAIP measures can be used as "biomarker" evidence that - in a given person - MEM is active within brain circuitry relevant to cognition. This study tests the hypothesis that the EAIP response to a "test dose" of MEM can be used to predict which patients with AD will be most vs. least sensitive to the clinical benefits of this medication over a 24-week trial.

Subjects with mild-to-moderate severity AD who meet criteria for study entry come to UCSD where consenting and a comprehensive screening and diagnostic assessment including a physical exam, EKG, and neuropsychological assessment are conducted. In addition, subjects are assessed on the Alzheimer's Disease Assessment Scale (ADAS-cog), which is the primary clinical outcome measure, and behavioral symptoms documented by the Neuropsychiatric Inventory (NPI-Q) and the Geriatric Depression Scale (GDS), which are secondary assessment measures. Blood is collected in order to assess APOE genotype (rs7412, rs429358) and characterize MEM-sensitive vs. -insensitive patients.

After initial screening, subjects return twice, approximately 7 days apart, for biomarker assessment after challenge with placebo (PBO) or memantine 20 mg po (MEM) in a double-blind, randomized order cross-over design. Subjects are assessed on prepulse inhibition of acoustic startle (PPI), mismatch negativity (MMN) and auditory steady state response (ASSR) as well as AD-relevant cognitive measures via the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Subjects then enter the "treatment phase." MEM is initiated at 5 mg/d and titrated with 5 mg weekly increments. During this time, subjects / caregivers are contacted weekly by study staff to assess adherence. Intervention Week 1 will begin when dosing reaches the full dose of 10 mg bid.

Subjects are reassessed on the primary (ADAS-cog) and secondary (NPI-Q and GDS) outcome measures after 8, 16 and 24 weeks of treatment at the full dose. Subjects are then offered the opportunity to remain at this dose of MEM, or to taper off MEM, under the care of their primary provider.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Memantine

EAIP are assessed 210 (PPI) and 345 min (MMN, ASSR) after administration of placebo or memantine (MEM 20 mg po), in a randomized order double-blind design. In this arm subjects are administered MEM 20 mg. Pills look identical so both the subject and research staff are blind to condition.

Group Type: OTHER

Memantine

Intervention Type: DRUG

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, 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.

Interventions

Memantine

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, 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Alzheimer's Disease Research Center-confirmed diagnosis of AD

2. Mini-Mental State Examination (MMSE) score 10-22 OR a Montreal Cognitive Assessment (MOCA) score of 15-24

3. Age 50-83 y

4. Knowledgeable caregiver

5. Ambulatory

6. Medically stable;

7. Audiometric testing (detection < or = to 45 db(A) at 1000 Hz)

8. Informed consent

Exclusion:

1. Active systemic illness (e.g. heart disease, liver failure, renal insufficiency, cancer, HIV, tuberculosis, Hepatitis C)

2. Current psychiatric or neurologic illness other than AD

3. History of vascular disease, myocardial infarction, cerebrovascular accidents, transient ischemic attack, seizure, head injury with loss of consciousness; substance dependence (including alcohol and Opioid)

4. Past treatment with memantine; unable to tolerate acetylcholinesterase inhibitor

5. Investigational drug treatment < 30 d of screening

6. Current meds: amantadine, riluzole, other pro-cognitive medication, opioids

7. Positive urine toxicology for non-prescribed psychoactive substance

8. Actively enrolled in cognitive remediation therapy

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 83 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Neal R. Swerdlow, M.D., Ph.D.

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Neal Swerdlow, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

UCSD

Locations

Clinical Teaching Facility (CTF-B102) at UCSD Medical Center

San Diego, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01AG059640-01

Identifier Type: NIH

Identifier Source: org_study_id

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