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

NCT00933608 | Completed Phase 4 Results

• 1 other identifier: NAM-MD-68
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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. 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. 2.The effects of the drug persist (as a marker of sustained neuroprotection) and can be measured 2 months after discontinuation of the treatment.

Conditions

Alzheimer's Disease

Keywords

subjective memory complaints; cognitively healthy; family history; AD

Outcome Measures

Primary Outcomes (1)

• 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)

Study Arms (2)

memantine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

dose increase to match active drug, after that 1 tablet in the morning, 1 tablet at night, to match active drug

Drug: Placebo

Interventions

memantine DRUG

participants will be asked to take memantine (20mg/day) for 16 weeks

Also known as: Namenda

memantine

Placebo DRUG

participants will be asked to take 2 tablets per day to match active drug

Placebo

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• presence of subjective memory complaints without objective evidence of impaired cognition
• family history of Alzheimer's disease

You may not qualify if:

• major depression
• Parkinson's disease
• stroke
• seizures
• uncontrolled diabetes or hypertension
• current benzodiazepine use
• substance abuse
• contraindication for MRI
• contraindications for memantine

Sponsors & Collaborators

• NYU Langone Health: lead
• Forest Laboratories: collaborator

Study Sites (1)

NYU School of Medicine, Dept. of Psychiatry, Center for Brain Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Memantine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Lidia Glodzik
• Organization: NYU School of Medicine

Lidia.Glodzik@nyumc.org

212.263.5698

Study Officials

• Lidia Glodzik, MD PhD

  NYU School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Research Professor

Study Record Dates

• First Submitted: July 2, 2009
• First Posted: July 7, 2009
• Study Start: July 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: October 21, 2014
• Results First Posted: October 21, 2014

Record last verified: 2014-10

Locations

US (1)