Alzheimer DiseasePhase 4NCT03703856
Biomarker Predictors of Memantine Sensitivity in Patients With Alzheimer's Disease
A Phase 4 study testing Memantine in people with Alzheimer Disease, run by University of California, San Diego at 1 site in United States.
Trial summary
The effects of the medication, memantine, on brain functions and the symptoms of Alzheimer's Disease will be tested Read more about this study
- Who is it for?
- Ages 50 to 83 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Memantine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2019to 30 Dec 2025
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 83 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 < or = to 45 db(A) at 1000 Hz)
- Informed consent
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Clinical Teaching Facility (CTF-B102) at UCSD Medical Center
San Diego, California, 92103
About this study
The effects of the medication, memantine, on brain functions and the symptoms of Alzheimer's Disease will be tested
Read the 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
- Being tested
- Memantine
- Keywords
- Alzheimer's Disease, Alzheimer Disease, Alzheimer, AD, Alzheimer's
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MemantineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Memantine | Other | 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. Receives: Drug: Memantine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 0, 8, 16, 24 weeks
Secondary outcomes (1)
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.
Measured: 0, 8, 16, 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2018
- Study start31 Jan 2019
- Primary completion8 Jan 2025
- Study completion30 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Neal R. Swerdlow, M.D., Ph.D., University of California, San Diego
- Investigators
- Neal Swerdlow, M.D., Ph.D., Principal investigator, UCSD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03703856
- Sponsor's protocol ID
- R01AG059640-01
- Status last verified
- Jul 2025
- First submitted
- 9 Oct 2018
- Last updated
- 16 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarker Predictors of Memantine Sensitivity in Patients With Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT03703856
- Acronym / sponsor ID
- R01AG059640-01
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer's Disease, Alzheimer Disease, Alzheimer, AD, Alzheimer's
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- 31 Jan 2019 (actual)
- Primary completion
- 8 Jan 2025 (actual)
- Study completion
- 30 Dec 2025 (actual)
- First posted
- 12 Oct 2018 (actual)
- Results
- Posted 7 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Memantine | Other | Drug: MemantineEAIP 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. |
Who may qualify
- Ages
- 50 to 83 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MemantinePhase 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. | Drug | Memantine |
Primary outcome
Change From Baseline Measure in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) at 8, 16 and 24 Weeks
Time frame: 0, 8, 16, 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.
1 secondary outcome
Change From Baseline Measure in Neuropsychiatric Inventory-Questionnaire (NPI-Q) at 8, 16 and 24 Weeks
Time frame: 0, 8, 16, 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Alzheimer Disease
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
RecruitingObservational study
Effectiveness and Safety of Disease-Modifying Therapy for Alzheimer's Disease: A Multicenter Retrospective Study
Alzheimer's Disease (AD)
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingPhase 3
A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease
Alzheimer's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Neal Swerdlow, M.D., Ph.D. principal investigator
UCSD
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Memantine in people with Alzheimer Disease, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline Measure in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) at 8, 16 and 24 Weeks (time frame: 0, 8, 16, 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2026.