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

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

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Memantine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Joyce Sprock; Phone Number: (619) 471-9455; Email: jsprock@ucsd.edu

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • Recruiting
      • Clinical Teaching Facility (CTF-B102) at UCSD Medical Center
      • Contact: Jo Talledo, B.A.; Phone Number: 619-543-3093; Email: atalledo@ucsd.edu
      • Principal Investigator: Neal R. Swerdlow, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 < 40 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 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.
Active Comparator: Memantine	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 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline measure in Geriatric Depression Scale (GDS) at 8, 16 and 24 weeks	measures behavioral symptoms	0, 8, 16, 24 weeks

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Neal Swerdlow, M.D., Ph.D., UCSD

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2019
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: October 9, 2018
• First Submitted That Met QC Criteria: October 10, 2018
• First Posted (Actual): October 12, 2018

Study Record Updates

• Last Update Posted (Estimated): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Alzheimer Disease; Alzheimer; AD; Alzheimer's
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Memantine
• Other Study ID Numbers: R01AG059640-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes