The purpose of the study is to examine patterns of brain activity in people who are at risk for memory problems (e.g., Alzheimer's disease or dementia)before and after the medication donepezil. Although genetic testing will be done, the results will not be shared with study participants. Once the genetic testing is completed subjects may continue to the second phase of the study. During this time...
Date First Received: December 5, 2006
Last Updated: April 16, 2009
Verified by: Vanderbilt University, April 2009
Clinical Trial Phase: Phase 1/Phase 2 | Start Date: December 2006
Overall Status: Recruiting
Estimated Enrollment: 30
Brief Summary
Official Title: “Efficacy of Donepezil in Normalizing Brain Activation Patterns in People Genetically at Risk for Alzheimer's Disease”
Condition Keyword(s):
Intervention(s):
The purpose of the study is to examine patterns of brain activity in people who are at risk for memory problems (e.g., Alzheimer's disease or dementia)before and after the medication donepezil. Although genetic testing will be done, the results will not be shared with study participants.
Once the genetic testing is completed subjects may continue to the second phase of the study.
During this time they will be asked to take the medication donepezil (which is approved by the FDA for the treatment of Alzheimer's disease).
Donepezil is not FDA approved for healthy volunteers and is therefore considered investigational in this study.
Study Type: Interventional
Study Design: Health Services Research, Non-Randomized, Open Label, Active Control, Single Group Assignment, Efficacy Study
Study Primary Completion Date: December 2010
Detailed Clinical Trial Description
HYPOTHESIS
1. Cognitively intact individuals with normal brain morphology at genetic risk for developing Alzheimer's' Disease (AD) show alterations in brain activation patterns during tasks that require memory compared to similar individuals with lower risk for developing AD.
2. Donepezil, a cholinesterase inhibitor, can normalize such brain activation patterns in subjects at risk for AD.
SPECIFIC AIMS
1. To replicate a recent study1, and compare brain activation in subjects genetically at risk for AD (carriers of the є4 allele of the apolipoprotein E gene (APOE)) with subjects at lower risk for AD (lacking the є4 allele) during tasks that require memory, via functional magnetic resonance imaging (fMRI).
2. To determine if administration of a drug currently indicated in the treatment of AD, donepezil, can reverse fMRI brain activation patterns of at risk subjects to patterns similar to those of subjects at lower genetic risk for AD.
Intervention(s) in this Clinical Trial
- Drug: donepezil
- donepezil 5 mg tablets, total dose per day 10 mg for 6 week duration of study. Taken once per day.
Arms, Groups and Cohorts in this Clinical Trial
- Experimental: 1
- Donepezil
Outcome Measures for this Clinical Trial
Primary Measures
- Changes in brain activation patterns as measured in an fMRI.
- Time Frame: 8 weeks
Safety Issue?: No
- Time Frame: 8 weeks
Criteria for Participation in this Clinical Trial
Inclusion Criteria:
- Subjects may report experiencing subjective memory dysfunction, however they must be found by clinical evaluation to have no memory dysfunction
- Neuropsychological test battery in the normal range
- Ages 40-85
Exclusion Criteria:
- Dementia (Mini-Mental State Exam less than 25/30)
- Left-handedness
- Current medication that could influence cognition
- Medical, psychiatric, and neurologic conditions, including cerebrovascular disease or uncontrolled hypertension
- Claustrophobia
- Surgical clips or implants
- Pacemakers or other implanted electronic devices
- History of sheet metal work
Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 40 Years
Maximum Age for this Clinical Trial: 85 Years
Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers
Clinical Trial Sponsor Information
Lead Sponsor: Vanderbilt University
Overall Clinical Trial Officials and Contacts
Harry E Gwirtsman, M.D. Principal Investigator Vanderbilt University
Overall Contact: Barbee Smith, B.A. 615-343-2009 barbee.smith@vanderbilt.edu
Related Publications
References
Bookheimer SY, Strojwas MH, Cohen MS, Saunders AM, Pericak-Vance MA, Mazziotta JC, Small GW. Patterns of brain activation in people at risk for Alzheimer's disease. N Engl J Med. 2000 Aug 17;343(7):450-6.
Morris JC. Is Alzheimer's disease inevitable with age?: Lessons from clinicopathologic studies of healthy aging and very mild alzheimer's disease. J Clin Invest. 1999 Nov;104(9):1171-3. Review. No abstract available.
Small GW, Mazziotta JC, Collins MT, Baxter LR, Phelps ME, Mandelkern MA, Kaplan A, La Rue A, Adamson CF, Chang L, et al. Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA. 1995 Mar 22-29;273(12):942-7.
Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D. Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med. 1996 Mar 21;334(12):752-8.
Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY, Lavretsky H, Miller K, Siddarth P, Rasgon NL, Mazziotta JC, Saxena S, Wu HM, Mega MS, Cummings JL, Saunders AM, Pericak-Vance MA, Roses AD, Barrio JR, Phelps ME. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6037-42.
Burggren AC, Small GW, Sabb FW, Bookheimer SY. Specificity of brain activation patterns in people at genetic risk for Alzheimer disease. Am J Geriatr Psychiatry. 2002 Jan-Feb;10(1):44-51.
Smith CD, Andersen AH, Kryscio RJ, Schmitt FA, Kindy MS, Blonder LX, Avison MJ. Women at risk for AD show increased parietal activation during a fluency task. Neurology. 2002 Apr 23;58(8):1197-202.
Padovani A, Pastorino L, Borroni B, Colciaghi F, Rozzini L, Monastero R, Perez J, Pettenati C, Mussi M, Parrinello G, Cottini E, Lenzi GL, Trabucchi M, Cattabeni F, Di Luca M. Amyloid precursor protein in platelets: a peripheral marker for the diagnosis of sporadic AD. Neurology. 2001 Dec 26;57(12):2243-8.
Borroni B, Colciaghi F, Pastorino L, Pettenati C, Cottini E, Rozzini L, Monastero R, Lenzi GL, Cattabeni F, Di Luca M, Padovani A. Amyloid precursor protein in platelets of patients with Alzheimer disease: effect of acetylcholinesterase inhibitor treatment. Arch Neurol. 2001 Mar;58(3):442-6.
Additional Information
Information obtained from ClinicalTrials.gov on July 02, 2009
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00408525
Study ID Number: 040686
ClinicalTrials.gov Identifier: NCT00408525
Health Authority: United States: Institutional Review Board
Clinical Trials Authorship and Review
Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.
