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

Effects of Memantine on the Magnetic Resonance Spectroscopy (MRS) Measures of Neuronal Integrity in Subjects at Risk for Alzheimer's Disease

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: memantine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU School of Medicine, Dept. of Psychiatry, Center for Brain Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
N-acetylaspartate	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.	baseline (pre-treatment) and 4 months (post-treatment)

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Forest Laboratories
• Investigators: Principal Investigator: Lidia Glodzik, MD PhD, NYU School of Medicine

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: July 2, 2009
• First Submitted That Met QC Criteria: July 6, 2009
• First Posted (Estimate): July 7, 2009

Study Record Updates

• Last Update Posted (Estimate): October 21, 2014
• Last Update Submitted That Met QC Criteria: October 20, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: AD; family history; subjective memory complaints; cognitively healthy
• 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: NAM-MD-68