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

• ClinicalTrials.gov Identifier: NCT03703856
• Recruitment Status: Recruiting
• First Posted: October 12, 2018
• Last Update Posted: March 3, 2021
• Sponsor: University of California, San Diego
• Information provided by (Responsible Party): Neal R. Swerdlow, M.D., Ph.D., University of California, San Diego

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease	Drug: Memantine; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Biomarker Predictors of Memantine Sensitivity in Patients With Alzheimer's Disease
• Actual Study Start Date: January 31, 2019
• Estimated Primary Completion Date: August 2023
• Estimated Study Completion Date: August 2023

Arms and Interventions

Arm	Intervention/treatment
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 88 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.
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 88 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.

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   measures cognitive ability

Secondary Outcome Measures :

1. Change from baseline measure in Neuropsychiatric Inventory-Questionnaire (NPI-Q) at 8, 16 and 24 weeks [ Time Frame: 0, 8, 16, 24 weeks ]
   measures behavioral symptoms

Other Outcome Measures:

1. Change from baseline measure in Geriatric Depression Scale (GDS) at 8, 16 and 24 weeks [ Time Frame: 0, 8, 16, 24 weeks ]
   measures behavioral symptoms

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Joyce Sprock; (619) 471-9455; jsprock@ucsd.edu

Locations

United States, California

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

San Diego, California, United States, 92103

Contact: Jo Talledo, B.A. 619-543-3093 atalledo@ucsd.edu

Principal Investigator: Neal R. Swerdlow, M.D., Ph.D.

Sponsors and Collaborators

University of California, San Diego

Investigators

• Principal Investigator: Neal Swerdlow, M.D., Ph.D.; UCSD

More Information

• Responsible Party: Neal R. Swerdlow, M.D., Ph.D., Principal Investigator, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT03703856
• Other Study ID Numbers: R01AG059640-01 ( U.S. NIH Grant/Contract )
• First Posted: October 12, 2018
• Last Update Posted: March 3, 2021
• Last Verified: March 2021

• 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

Keywords provided by Neal R. Swerdlow, M.D., Ph.D., University of California, San Diego:

Alzheimer's Disease; Alzheimer Disease; Alzheimer; AD; Alzheimer's

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Memantine; Antiparkinson Agents; Anti-Dyskinesia Agents; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents