Corticolimbic Degeneration and Treatment of Dementia

• ClinicalTrials.gov Identifier: NCT00768261
• Recruitment Status: Completed
• First Posted: October 8, 2008
• Results First Posted: September 11, 2018
• Last Update Posted: September 11, 2018
• Sponsor: Washington University School of Medicine
• Collaborator: Northwestern University
• Information provided by (Responsible Party): Washington University School of Medicine

Tracking Information

• First Submitted Date: October 7, 2008
• First Posted Date: October 8, 2008
• Results First Submitted Date: April 24, 2018
• Results First Posted Date: September 11, 2018
• Last Update Posted Date: September 11, 2018
• Study Start Date: November 2004
• Actual Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 9, 2018): Rate of Change of Hippocampal Volume Slope [ Time Frame: 2 years ]
• Original Primary Outcome Measures (submitted: October 7, 2008): 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 ]

Current Secondary Outcome Measures (submitted: August 9, 2018)

Comparison of Combined DAT Patients' Mean (SD) Hippocampal Volume Slope (mm^3/Year) Rate of Change [ Time Frame: two years ]

The ADAS-Cog evaluates cognition and differentiates normal from impaired cognitive functioning. The total score is the summed number of errors in each task. The greater the impairment, the greater the score. We combined the dementia of the Alzheimer's type patients receiving all treatments together and grouped them into 3 subgroups according to the rates of change(roc) of their ADAS-Cog scores. To determine trends in hippocampal volume atrophy over time we compared the patients showing most negative ADAS-Cog rate of change (improving), patients with most positive ADAS-cog roc (worsening), patients with intermediate, near-zero ADAS-Cog roc (stable) .

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Corticolimbic Degeneration and Treatment of Dementia
• Official Title: Corticolimbic Degeneration and Treatment of Dementia
• 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.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Dementia

Intervention

• 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: Donepezil (Aricept®)
  5mg/day for six weeks and if no serious side-effects increased to 10mg/dy.
  Other Name: Aricept

Study Arms

• No Intervention: Very Mild to Mild DAT Untreated
  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: Very Mild-Mild DAT Treated W/ Donepezil
  Group 2) subjects with very mild (CDR 0.5) to mild (CDR 1) DAT that are treated with Donepezil (Aricept®).
  Intervention: Drug: Donepezil (Aricept®)
• Active Comparator: Very Mild-Mild DAT Treated W/Combination
  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®)
  Interventions:

  • Drug: Memantine (Namenda®)
  • Drug: Donepezil (Aricept®)
• No Intervention: Nondemented Comparison Subjects
  Group 4) nondemented comparison subjects.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 2, 2011): 39
• Original Estimated Enrollment (submitted: October 7, 2008): 50
• Actual Study Completion Date: October 2009
• Actual Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 95 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT00768261
• Other Study ID Numbers: 5R01MH060883-06( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Washington University School of Medicine
• Original Responsible Party: James Galvin, MD. MPH, Washington University School of Medicine
• Current Study Sponsor: Washington University School of Medicine
• Original Study Sponsor: Same as current
• Collaborators: Northwestern University

Investigators

• Principal Investigator: John Morris, MD; Washington University School of Medicine

• PRS Account: Washington University School of Medicine
• Verification Date: August 2018