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

Alzheimer's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00369603
• Other study ID #: Pro00011149
• Secondary ID: GAL-EMR-4026
• Status: Terminated
• Phase: Phase 4
• First received: August 28, 2006
• Last updated: April 9, 2013
• Start date: October 2006
• Est. completion date: November 2007

Study information

• Verified date: June 2008
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: November 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 90 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

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

Locations

Country	Name	City	State
United States	Joseph & Kathleen Bryan Alzheimer's Disease Research Unit	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Ortho-McNeil Neurologics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		4-weeks and 12-weeks	No
Secondary	Differences in cognitive testing and functional status at pre-treatment baseline and after completion of the 12-week treatment trial.		baseline and 12-weeks	No