A Phase 4 interventional study of Memantine in Alzheimer Disease, sponsored by University of California, San Diego. Completed at 1 site in United States. Open to participants aged 50 Years to 83 Years. Per ClinicalTrials.gov, last updated 2026-04-16.
Sponsored by University of California, San Diego · Phase 4, Interventional, and Treatment
The effects of the medication, memantine, on brain functions and the symptoms of Alzheimer's Disease will be tested
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.
3,675 studies on the registry are indexed under Alzheimer Disease; 869 are open to participants now.
This study's enrollment of 53 is below the median of 70 across 2,805 interventional studies indexed under Alzheimer Disease.
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Of its 110 completed or terminated interventional studies of FDA-regulated products, 70 (64%) have results posted.
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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.
Drug: 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.
Change From Baseline Measure in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) at 8, 16 and 24 Weeks
The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is a tool used to assess the severity of cognitive impairment in individuals with Alzheimer's disease. It includes 11 tasks that evaluate memory, language, and praxis. The total score can range from 0 to 70 with higher scores indicating more severe impairment.
Time frame: 0, 8, 16, 24 weeks
Change From Baseline Measure in Neuropsychiatric Inventory-Questionnaire (NPI-Q) at 8, 16 and 24 Weeks
The NPI-Q measures behavioral symptoms in and is a self-administered questionnaire completed by informants about patients for whom they care. Each of the 12 NPI-Q domains contains a survey question that reflects cardinal symptoms of that domain. Symptoms are rated as present or absent, and if they are present the informant rates the severity of the symptom on a 3-point scale from mild to severe. The sum of severity scores across all 12 items ranges from 0 to 36 with higher scores indicate higher severity of symptoms.
Time frame: 0, 8, 16, 24 weeks
Change From Baseline Measure in Geriatric Depression Scale (GDS) at 8, 16 and 24 Weeks
The Geriatric Depression Scale (GDS) is a self-report measure of depression in older adults using a "Yes/No" format. The GDS consists of 30 items with higher scores indicating greater levels or depression. A score of 0-9 is normal, 10-19 is mild depression, and 20-30 is severe depression.
Time frame: 0, 8, 16, 24 weeks
| Milestone | Memantine |
|---|---|
| Started | 53 |
| Completed | 30 |
| Not completed | 23 |
| Withdrew: Withdrawal by subject | 23 |
| Milestone | Memantine |
|---|---|
| Started | 30 |
| Completed | 25 |
| Not completed | 5 |
| Withdrew: Withdrawal by subject | 5 |
| Milestone | Memantine |
|---|---|
| Started | 25 |
| Completed | 25 |
| Not completed | 0 |
| Milestone | Memantine |
|---|---|
| Started | 25 |
| Completed | 24 |
| Not completed | 1 |
| Withdrew: Withdrawal by subject | 1 |
| Milestone | Memantine |
|---|---|
| Started | 24 |
| Completed | 23 |
| Not completed | 1 |
| Withdrew: Withdrawal by subject | 1 |
The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is a tool used to assess the severity of cognitive impairment in individuals with Alzheimer's disease. It includes 11 tasks that evaluate memory, language, and praxis. The total score can range from 0 to 70 with higher scores indicating more severe impairment.
| scores on a scale | Memantine |
|---|---|
| Baseline | 19.76 ± 8.97 |
| Week 8 | 19.81 ± 9.85 |
| Week 16 | 19.94 ± 9.55 |
| Week 24 | 20.79 ± 11.03 |
The NPI-Q measures behavioral symptoms in and is a self-administered questionnaire completed by informants about patients for whom they care. Each of the 12 NPI-Q domains contains a survey question that reflects cardinal symptoms of that domain. Symptoms are rated as present or absent, and if they are present the informant rates the severity of the symptom on a 3-point scale from mild to severe. The sum of severity scores across all 12 items ranges from 0 to 36 with higher scores indicate higher severity of symptoms.
| score on a scale | Memantine |
|---|---|
| Baseline | 4.27 ± 4.05 |
| Week 8 | 3.55 ± 3.36 |
| Week 16 | 3.05 ± 2.38 |
| Week 24 | 4.09 ± 3.57 |
The Geriatric Depression Scale (GDS) is a self-report measure of depression in older adults using a "Yes/No" format. The GDS consists of 30 items with higher scores indicating greater levels or depression. A score of 0-9 is normal, 10-19 is mild depression, and 20-30 is severe depression.
| score on a scale | Memantine |
|---|---|
| Baseline | 6.23 ± 5.66 |
| Week 8 | 6.05 ± 5.92 |
| Week 16 | 6.09 ± 6.69 |
| Week 24 | 6.64 ± 6.89 |
Collected over From enrollment until end of last visit at 24 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Memantine | 0/53 (0%) | 2/53 (3.8%) | 13/53 (24.5%) |
| Event | Memantine |
|---|---|
| Abnormal blood test presumed Chronic Lymphocytic LeukemiaBlood and lymphatic system disorders | 1/53 |
| Positive prostate biopsyReproductive system and breast disorders | 1/53 |
| Event | Memantine |
|---|---|
| FatigueGeneral disorders | 4/53 |
| DizzinessGeneral disorders | 3/53 |
| NauseaGastrointestinal disorders | 2/53 |
| Weight lossGeneral disorders | 2/53 |
| ConstipationGastrointestinal disorders | 2/53 |
| TinnitisEar and labyrinth disorders | 2/53 |
| FallInjury, poisoning and procedural complications | 1/53 |
| Bump in left earEar and labyrinth disorders | 1/53 |
| Facial rashSkin and subcutaneous tissue disorders | 1/53 |
| Foot crampsMusculoskeletal and connective tissue disorders | 1/53 |
Includes all subjects consented/enrolled in the study
| Age, Continuous(years) | Memantine |
|---|---|
| Mean | 71.61 ± 6.89 |
| Sex: Female, Male(Participants) | Memantine |
|---|---|
| Female | 27 |
| Male | 26 |
| Ethnicity (NIH/OMB)(Participants) | Memantine |
|---|---|
| Hispanic or Latino | 4 |
| Not Hispanic or Latino | 48 |
| Unknown or Not Reported | 1 |
| Race (NIH/OMB)(Participants) | Memantine |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 2 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 3 |
| White | 42 |
| More than one race | 0 |
| Unknown or Not Reported | 6 |
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University of California, San Diego