Official Title: “Corticolimbic Degeneration and Treatment of Dementia”

The overall purpose of this research is to determine if there is a relationship between your symptoms of Dementia of the Alzheimers type and changes in the size and shape of certain brain structures during combined Donepezil (Aricept®) and Memantine (Namenda®) treatment.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study

Study Primary Completion Date: October 2009

In this study we will be using Memantine (Namenda®) in an investigational fashion with individuals with very mild to mild dementia. Donepezil (Aricept®) is approved by the Food and Drug Administration for the treatment of Alzheimers disease. Memantine (Namenda®) is currently approved by the Food and Drug Administration for moderate and severe dementia only.

This study may be instrumental in the development of a new therapy for others with similar conditions, and to determine whether Memantine (Namenda®) will be helpful to individuals with very mild to mild dementia.

Specific Aim 1. To determine what neuroanatomical measures are most strongly correlated with the progression of clinical and cognitive deficits in patients with dementia of the Alzheimer type (DAT). To accomplish this aim, we will use high-resolution magnetic resonance (MR) imaging and the tools of computational anatomy to assess changes in the structure of selected subcortical (e.g., hippocampus) and cortical (e.g., parahippocampal gyrus and cingulate gyrus) structure along with clinical and cognitive measures of dementia severity in subjects with very mild-to-mild DAT. Specific Aim 2 - To determine whether cholinesterase inhibitors and memantine can slow disease progression in DAT subjects. To accomplish this aim, we will use MR imaging and the tools of computational anatomy to compare the rate of change in the neuroanatomical measures listed above in 1) untreated DAT subjects, 2) DAT subjects treated with donepezil alone, and 3) DAT subjects treated with the combination of donepezil and memantine.

Intervention(s) in this Clinical Trial

• Drug: Memantine (Namenda®)
  • Drug treatment will begin with 5 mg/day of donepezil for six weeks. After six weeks of such treatment, the subjects symptoms will be re-evaluated and any side-effects of treatment assessed and recorded. If no serious side-effects of donepezil are encountered, the dose of donepezil will be increased to 10 mg/day. For subjects prescribed the combination of donepezil and memantine, memantine (20 mg/day) will be added to the drug treatment regimen after the dose of donepezil has been established (i.e., at six weeks). Again, memantine will be initially started at 10 mg/day and increased to its full dose only if no serious side-effects are encountered.
• Drug: Memantine (Namenda®)
  • Initial dose of 10mg/day and increased to full dose of 20mg/day if no serious side-effects
• Drug: Donepezil (Aricept®)
  • 5mg/day for six weeks and if no serious side-effects increased to 10mg/dy.

Arms, Groups and Cohorts in this Clinical Trial

• No Intervention: 1
  • Group 1) subjects with very mild (CDR 0.5) to mild (CDR 1) DAT that are untreated with either cholinesterase inhibitors or memantine
• Active Comparator: 2
  • Group 2) subjects with very mild (CDR 0.5) to mild (CDR 1) DAT that are treated with donepezil.
• Active Comparator: 3
  • Group 3) subjects with very mild (CDR 0.5) to mild (CDR 1) DAT that are treated with the combination of donepezil and memantine.
• No Intervention: 4
  • Group 4) nondemented comparison subjects.

Primary Measures

• The volume and shape of the hippocampus could predict the outcome of treatment with donepezil in patients with very mild-to-mild DAT.
  • Time Frame: two years
    Safety Issue?: No

• Inclusion Criteria: 1) meets NINCDS-ADRDA criteria for DAT, 2) CDR score of 0.5 or 1, 3) 50-80 years of age, 4) able to give informed consent or has a primary caregiver or legal guardian, who can give informed consent.
• Exclusion Criteria: 1) other psychiatric (e.g., depression) or neurological (e.g., CVA) disorders that would confound the assessment of dementia symptoms, 2) history of loss of consciousness, and 3) unstable or severe medical illness (e.g., hepatotoxicity) that would make donepezil or memantine treatment or participation in other aspects of the study unsafe.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: 95 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Washington University School of Medicine

Overall Clinical Trial Officials and Contacts

James Galvin, MD, MPH Principal Investigator Washington University School of Medicine  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00768261

Study ID Number: 5R01MH060883-06

ClinicalTrials.gov Identifier: NCT00768261

Health Authority: United States: Institutional Review Board