Corticolimbic Degeneration and Treatment of Dementia

Corticolimbic Degeneration and Treatment of Dementia

Sponsors

Lead Sponsor: Washington University School of Medicine

Collaborator: Northwestern University

Source Washington University School of Medicine
Brief Summary

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.

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.

Overall Status Completed
Start Date November 2004
Completion Date October 2009
Primary Completion Date October 2009
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Rate of Change of Hippocampal Volume Slope 2 years
Secondary Outcome
Measure Time Frame
Comparison of Combined DAT Patients' Mean (SD) Hippocampal Volume Slope (mm^3/Year) Rate of Change two years
Enrollment 39
Condition
Intervention

Intervention Type: Drug

Intervention Name: Memantine (Namenda®)

Description: 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.

Arm Group Label: Very Mild-Mild DAT Treated W/Combination

Other Name: Namenda

Intervention Type: Drug

Intervention Name: Donepezil (Aricept®)

Description: 5mg/day for six weeks and if no serious side-effects increased to 10mg/dy.

Other Name: Aricept

Eligibility

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.

Gender: All

Minimum Age: 50 Years

Maximum Age: 95 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
John Morris, MD Principal Investigator Washington University School of Medicine
Verification Date

August 2018

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Very Mild to Mild DAT Untreated

Type: No Intervention

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

Label: Very Mild-Mild DAT Treated W/ Donepezil

Type: Active Comparator

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

Label: Very Mild-Mild DAT Treated W/Combination

Type: Active Comparator

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®)

Label: Nondemented Comparison Subjects

Type: No Intervention

Description: Group 4) nondemented comparison subjects.

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov