Official Title: “Functional Neuroimaging (fMRI) Biomarker of Allosteric Nicotinic Receptor Modulation in Mild Alzheimer's Disease Patients: A Razadyne vs. Aricept Dose Escalation Trial”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Dose Comparison, Parallel Assignment, Pharmacodynamics Study

Study Primary Completion Date: October 2007

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.

Intervention(s) in this Clinical Trial

• Drug: Razadyne ER
  • 4-weeks 8mg. Razadyne ER, then 4-weeks 16mg. Razadyne ER, and a subsequent 4-weeks of 24mg. Razadyne ER
• Drug: Aricept
  • 8-weeks 5mg. Aricept and a subsequent 4-weeks of 10mg. Aricept

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Razadyne ER
  • galantamine treatment group
• Experimental: Aricept
  • Aricept Treatment Group

Primary 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
    Safety Issue?: No

Secondary 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
    Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 90 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Duke University

Overall Clinical Trial Officials and Contacts

Jeffrey N Browndyke, PhD Principal Investigator Duke University  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00369603

Study ID Number: GAL-EMR-4026

ClinicalTrials.gov Identifier: NCT00369603

Health Authority: United States: Institutional Review Board