Summary

Eligibility
for people ages 50-83 (full criteria)
Location
at UCSD
Dates
study started
study ends around
Principal Investigator
by Neal Swerdlow, M.D., Ph.D. (ucsd)
Headshot of Neal Swerdlow
Neal Swerdlow

Description

Summary

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

Details

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.

Keywords

Alzheimer Disease, Alzheimer's Disease, Alzheimer, AD, Alzheimer's, Memantine, Counterfeit Drugs

Eligibility

For people ages 50-83

Inclusion:

  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

Location

  • Clinical Teaching Facility (CTF-B102) at UCSD Medical Center
    San Diego 5391811 California 5332921 92103 United States

Lead Scientist at University of California Health

  • Neal Swerdlow, M.D., Ph.D. (ucsd)
    Neal Swerdlow, M.D., Ph.D. is Distinguished Professor of Psychiatry and Director of the Research Residency Track in the Department of Psychiatry at the University of California, San Diego, School of Medicine. Dr. Swerdlow graduated Summa Cum Laude, Phi Beta Kappa, from Amherst College (Neuroscience) in 1981, received his M.D. and Ph.D.

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Diego
ID
NCT03703856
Phase
Phase 4 Alzheimer's Disease Research Study
Study Type
Interventional
Participants
About 32 people participating
Last Updated