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

Alzheimer's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00933608
• Other study ID #: NAM-MD-68
• Status: Completed
• Phase: Phase 4
• First received: July 2, 2009
• Last updated: October 20, 2014
• Start date: July 2009
• Est. completion date: September 2011

Study information

• Verified date: October 2014
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 55 Years to 90 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• memantine
participants will be asked to take memantine (20mg/day) for 16 weeks
• Placebo
participants will be asked to take 2 tablets per day to match active drug

Locations

Country	Name	City	State
United States	NYU School of Medicine, Dept. of Psychiatry, Center for Brain Health	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York University School of Medicine	Forest Laboratories

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No