Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

July 2, 2009
October 20, 2014
July 2009
September 2011   (final data collection date for primary outcome measure)
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.
changes in N-acetylaspartate and glutamate [ Time Frame: 4 and 6 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00933608 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
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.
Not Provided
Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Alzheimer's Disease
  • Drug: memantine
    participants will be asked to take memantine (20mg/day) for 16 weeks
    Other Name: Namenda
  • Drug: Placebo
    participants will be asked to take 2 tablets per day to match active drug
    Other Name: Placebo
  • 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
    Intervention: Drug: memantine
  • Placebo Comparator: Placebo
    dose increase to match active drug, after that 1 tablet in the morning, 1 tablet at night, to match active drug
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
17
September 2011
September 2011   (final data collection date for primary outcome measure)

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
Both
55 Years to 90 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00933608
NAM-MD-68
Not Provided
Lidia Glodzik, New York University School of Medicine
New York University School of Medicine
Forest Laboratories
Principal Investigator: Lidia Glodzik, MD PhD NYU School of Medicine
New York University School of Medicine
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP