Corticolimbic Degeneration and Treatment of Dementia

This study has been completed.
Sponsor:
Collaborator:
Northwestern University
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00768261
First received: October 7, 2008
Last updated: July 19, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Dementia
Drug: Memantine (Namenda®)
Drug: Donepezil (Aricept®)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Corticolimbic Degeneration and Treatment of Dementia

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome 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 ] [ Designated as safety issue: No ]

Enrollment: 39
Study Start Date: November 2004
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Donepezil (Aricept®)
5mg/day for six weeks and if no serious side-effects increased to 10mg/dy.
Other Name: Aricept
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.
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.
Other Name: Namenda
Drug: Memantine (Namenda®)
Initial dose of 10mg/day and increased to full dose of 20mg/day if no serious side-effects
Other Name: Namenda
No Intervention: 4
Group 4) nondemented comparison subjects.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   50 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00768261

Sponsors and Collaborators
Washington University School of Medicine
Northwestern University
Investigators
Principal Investigator: John Morris, MD Washington University School of Medicine
  More Information

No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00768261     History of Changes
Other Study ID Numbers: 5R01MH060883-06
Study First Received: October 7, 2008
Last Updated: July 19, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
Dementia of the Alzheimer type

Additional relevant MeSH terms:
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Donepezil
Memantine
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents

ClinicalTrials.gov processed this record on October 01, 2014