Corticolimbic Degeneration and Treatment of Dementia

The Washington University

Status and phase: Completed; Phase 4

Conditions: Dementia

Treatments: Drug: Memantine (Namenda®); Drug: Donepezil (Aricept®)

Study type: Interventional

Funder types: Other

Identifiers

NCT00768261

5R01MH060883-06

Details and patient eligibility

About

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.

Full 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.

Enrollment: 39 patients

Sex: All

Ages: 50 to 95 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: 1) meets National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association(NINCDS-ADRDA) Alzheimer's criteria for dementia of the Alzheimer's type (DAT), 2) Clinical Dementia Rating (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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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39 participants in 4 patient groups

Very Mild to Mild DAT Untreated

No Intervention group

Description:

Group 1) subjects with very mild (CDR 0.5) to mild (CDR 1) DAT that are untreated with either cholinesterase inhibitors or memantine

Very Mild-Mild DAT Treated W/ Donepezil

Active Comparator group

Description:

Group 2) subjects with very mild (CDR 0.5) to mild (CDR 1) DAT that are treated with Donepezil (Aricept®).

Treatment:

Drug: Donepezil (Aricept®)

Very Mild-Mild DAT Treated W/Combination

Active Comparator group

Description:

Group 3) subjects with very mild (CDR 0.5) to mild (CDR 1) DAT that are treated with the combination of Donepezil (Aricept®) and Memantine (Namenda®)

Treatment:

Drug: Donepezil (Aricept®)

Drug: Memantine (Namenda®)

Nondemented Comparison Subjects

No Intervention group

Description:

Group 4) nondemented comparison subjects.