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Effects of Memantine on Magnetic Resonance (MR) Spectroscopy in Subjects at Risk for Alzheimer's Disease

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Lidia Glodzik, New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00933608
First received: July 2, 2009
Last updated: October 20, 2014
Last verified: October 2014
  Purpose

Recent data show that marked cell damage precedes the clinical manifestation of Alzheimer's disease (AD). Hence, targeting populations at risk with pharmacological interventions is a possible strategy to lessen the burden of the disease. Cognitively normal individuals with subjective memory complaints (SMC) manifest biological characteristics consistent with early AD and are at risk for future cognitive decline. Family history of AD also constitutes a risk. In a previous study the investigators showed that memantine slows down the accumulation of phosphorylated tau in normal SMC subjects. Using a multivoxel high field MR spectroscopy (MRS) technique, the investigators also demonstrated that memantine decreased hippocampal glutamate. Both these findings may be consistent with the drug's anti-excitotoxic activity. In this new project the investigators propose to treat a sample of 12 presymptomatic individuals at risk (SMC and family history of AD) with memantine. This will be a double blind, placebo controlled study with a control group (12 non-treated subjects). The investigators will determine whether the effects of memantine as assessed by cognitive performance and MRS are present after 4 months of treatment and persist 2 months after discontinuation. MRS will be used to evaluate the effect of memantine on levels of the neurotransmitter glutamate and neuronal viability marker N-acetylaspartate (NAA) in the hippocampus. The investigators will test the following hypotheses:

  1. In subjects with SMC, memantine has modifying effects on brain biochemistry as reflected in MRS reductions in glutamate (reduced excitotoxicity) and increases in NAA (neuronal integrity).
  2. The effects of the drug persist (as a marker of sustained neuroprotection) and can be measured 2 months after discontinuation of the treatment.

Condition Intervention Phase
Alzheimer's Disease
Drug: memantine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Effects of Memantine on the Magnetic Resonance Spectroscopy (MRS) Measures of Neuronal Integrity in Subjects at Risk for Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • N-acetylaspartate [ Time Frame: baseline (pre-treatment) and 4 months (post-treatment) ] [ Designated as safety issue: No ]
    The change in N-acetylaspartate (NAA) measured with magnetic resonance spectroscopy (MRS) is the primary outcome measure. NAA is a metabolite found predominately in neuronal cells, and its amount indicates tissue well being (the higher the better). In MRS studies NAA (and other metabolites like choline or myoinositol) are presented as a ratio to creatine (Cr) also measured by MRS. The concentration of creatine does not change is used as an internal standard. The ratio NAA/Cr is unitless. In summary, the measurable outcome will be the NAA/Cr ratio change from pre-to post treatment.


Enrollment: 17
Study Start Date: July 2009
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: memantine
after a period of gradual dose increase from 5 mg/day, participants will be asked to take memantine (20mg/day) for 16 weeks 10 mg in the morning, 10 mg at night
Drug: memantine
participants will be asked to take memantine (20mg/day) for 16 weeks
Other Name: Namenda
Placebo Comparator: Placebo
dose increase to match active drug, after that 1 tablet in the morning, 1 tablet at night, to match active drug
Drug: Placebo
participants will be asked to take 2 tablets per day to match active drug
Other Name: Placebo

  Eligibility

Ages Eligible for Study:   55 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • presence of subjective memory complaints without objective evidence of impaired cognition
  • family history of Alzheimer's disease

Exclusion Criteria:

  • major depression
  • Parkinson's disease
  • stroke
  • seizures
  • uncontrolled diabetes or hypertension
  • current benzodiazepine use
  • substance abuse
  • contraindication for MRI
  • contraindications for memantine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00933608

Locations
United States, New York
NYU School of Medicine, Dept. of Psychiatry, Center for Brain Health
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Forest Laboratories
Investigators
Principal Investigator: Lidia Glodzik, MD PhD NYU School of Medicine
  More Information

No publications provided

Responsible Party: Lidia Glodzik, Assistant Research Professor, New York University School of Medicine
ClinicalTrials.gov Identifier: NCT00933608     History of Changes
Other Study ID Numbers: NAM-MD-68
Study First Received: July 2, 2009
Results First Received: May 8, 2013
Last Updated: October 20, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
subjective memory complaints
cognitively healthy
family history
AD

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies
Memantine
Anti-Dyskinesia Agents
Antiparkinson Agents
Central Nervous System Agents
Dopamine Agents
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014