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

This study has been terminated.
(Reduced access to AchEI medication-naive mild AD patients.)
Sponsor:
Collaborator:
Ortho-McNeil Neurologics, Inc.
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00369603
First received: August 28, 2006
Last updated: April 9, 2013
Last verified: June 2008
History of Changes
  Purpose

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 Intervention Phase
Alzheimer's Disease
 Drug: Razadyne ER
Drug: Aricept
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 4
Study Start Date: October 2006
Study Completion Date: November 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   40 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00369603

Locations
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.
Investigators
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
  More Information

No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00369603     History of Changes
Other Study ID Numbers: Pro00011149, GAL-EMR-4026
Study First Received: August 28, 2006
Last Updated: April 9, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Alzheimer's Disease
fMRI
Functional Neuroimaging
Allosteric Nicotinic Receptor Modulation
 Acetylcholinesterase Inhibition
Head to head
Dose escalation
Biomarker

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Galantamine
Donepezil
Parasympathomimetics
 Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on May 16, 2013