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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00933608
Recruitment Status : Completed
First Posted : July 7, 2009
Results First Posted : October 21, 2014
Last Update Posted : October 21, 2014
Forest Laboratories
Information provided by (Responsible Party):
Lidia Glodzik, NYU Langone Health

Brief Summary:

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 or disease Intervention/treatment Phase
Alzheimer's Disease Drug: memantine Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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
Study Start Date : July 2009
Actual Primary Completion Date : September 2011
Actual Study Completion Date : September 2011

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. N-acetylaspartate [ Time Frame: baseline (pre-treatment) and 4 months (post-treatment) ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00933608

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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
NYU Langone Health
Forest Laboratories
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Principal Investigator: Lidia Glodzik, MD PhD NYU School of Medicine
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Responsible Party: Lidia Glodzik, Assistant Research Professor, NYU Langone Health Identifier: NCT00933608    
Other Study ID Numbers: NAM-MD-68
First Posted: July 7, 2009    Key Record Dates
Results First Posted: October 21, 2014
Last Update Posted: October 21, 2014
Last Verified: October 2014
Keywords provided by Lidia Glodzik, NYU Langone Health:
subjective memory complaints
cognitively healthy
family history
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
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