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Functional Brain Imaging of Medication Treatment Response in Mild Alzheimer's Disease Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00369603
Recruitment Status : Terminated (Reduced access to AchEI medication-naive mild AD patients.)
First Posted : August 29, 2006
Last Update Posted : April 11, 2013
Ortho-McNeil Neurologics, Inc.
Information provided by (Responsible Party):
Duke University

Brief Summary:
The purpose of this study is to determine whether standard medications approved for Alzheimer's disease treatment differ in their action on brain functioning and whether any observed brain activity differences as result of treatment are associated with particular patterns of dementia improvement or reduced decline.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Razadyne ER Drug: Aricept Phase 4

Detailed Description:

This study seeks to differentiate task-related and resting brain activity patterns captured via functional magnetic resonance imaging (fMRI) and associated with two common Alzheimer's disease (AD) medications, equivalent in acetylcholinesterase inhibition effect (AChEI) but differing with respect to allosteric nicotinic receptor modulation effect. It is the primary aim of this project to gain a better understanding of the brain mechanisms involved in the attentional and executive skills improvements associated with nicotinic receptor modulation in mild AD patients.

To address this question, this 12-week continuous treatment, double-blind, head-to-head dose-escalation treatment trial seeks to visualize any treatment response unique to allosteric nicotinic receptor modulation and to associate these fMRI data with standard cognitive assessment outcomes. Using in-scanner tasks shown to reliably elicit brain activity in cortical regions important to memory and attention, this treatment trial will examine both resting and task-related BOLD signal characteristics in a well-characterized sample of 36 mild AD patients after periods of low dose and high dose AD dementia treatment with either galantamine hydrobromide (AChEI + nicotinic receptor modulation) or donepezil hydrochloride (AChEI only). Both the low and high dose imaging comparisons between treatment groups will be equivalent for 35% AChEI-effect, which may allow for the isolation of BOLD signal unique to allosteric nicotinic receptor modulation in both brain at rest and task-related brain states.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Functional Neuroimaging (fMRI) Biomarker of Allosteric Nicotinic Receptor Modulation in Mild Alzheimer's Disease Patients: A Razadyne vs. Aricept Dose Escalation Trial
Study Start Date : October 2006
Actual Primary Completion Date : October 2007
Actual Study Completion Date : November 2007

Arm Intervention/treatment
Experimental: Razadyne ER
galantamine treatment group
Drug: Razadyne ER
4-weeks 8mg. Razadyne ER, then 4-weeks 16mg. Razadyne ER, and a subsequent 4-weeks of 24mg. Razadyne ER

Experimental: Aricept
Aricept Treatment Group
Drug: Aricept
8-weeks 5mg. Aricept and a subsequent 4-weeks of 10mg. Aricept

Primary Outcome Measures :
  1. Brain activity patterns, as collected via functional magnetic resonance imaging (fMRI), at rest and associated with task performance after 4 weeks of low-dose treatment and after 8-weeks of higher-dose treatment. [ Time Frame: 4-weeks and 12-weeks ]

Secondary Outcome Measures :
  1. Differences in cognitive testing and functional status at pre-treatment baseline and after completion of the 12-week treatment trial. [ Time Frame: baseline and 12-weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Must meet diagnosis of mild Alzheimer's disease
  • Must have a family member or caregiver who is willing to attend all study visits and provide information on your participation in the study
  • If female, must be post-menopausal
  • Must be able to swallow tablets

Exclusion Criteria:

  • Metal implants or medical devises unsafe for MRI use
  • Pre-menopausal female
  • HIstory of recent head injury
  • Significant major, life-threatening illness or injury (e.g., stroke, AIDS, etc.)
  • Vascular dementia or any dementia other than Alzheimer's Disease
  • History of significant alcoholism or drug abuse
  • History of seizure disorder, developmental delay or major psychiatric illness

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00369603

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United States, North Carolina
Joseph & Kathleen Bryan Alzheimer's Disease Research Unit
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Duke University
Ortho-McNeil Neurologics, Inc.
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Principal Investigator: Jeffrey N Browndyke, PhD Duke University
Principal Investigator: Roberto Cabeza, PhD Duke University
Principal Investigator: James R Burke, PhD Duke University
Principal Investigator: Kathleen Welsh-Bohmer, PhD Duke University
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Responsible Party: Duke University Identifier: NCT00369603    
Other Study ID Numbers: Pro00011149
GAL-EMR-4026 ( Other Identifier: DUMC )
First Posted: August 29, 2006    Key Record Dates
Last Update Posted: April 11, 2013
Last Verified: June 2008
Keywords provided by Duke University:
Alzheimer's Disease
Functional Neuroimaging
Allosteric Nicotinic Receptor Modulation
Acetylcholinesterase Inhibition
Head to head
Dose escalation
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents
Autonomic Agents
Peripheral Nervous System Agents