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

• ClinicalTrials.gov Identifier: NCT00933608
• Recruitment Status: Completed
• First Posted: July 7, 2009
• Results First Posted: October 21, 2014
• Last Update Posted: October 21, 2014
• Sponsor: NYU Langone Health
• Collaborator: Forest Laboratories
• Information provided by (Responsible Party): Lidia Glodzik, NYU Langone Health

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

• Ages Eligible for Study: 55 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

NYU Langone Health

Forest Laboratories

Investigators

• Principal Investigator: Lidia Glodzik, MD PhD; NYU School of Medicine

More Information

• Responsible Party: Lidia Glodzik, Assistant Research Professor, NYU Langone Health
• ClinicalTrials.gov Identifier: NCT00933608
• Other Study ID Numbers: NAM-MD-68
• First Posted: July 7, 2009
• 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; AD

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