- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00486044
Evaluating Simvastatin's Potential Role in Therapy (ESPRIT)
Effect of Statins on Pathobiology of Alzheimer's Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Some studies suggest that statin medications, which are a group of cholesterol-lowering medicines, may help prevent Alzheimer's disease. However, this has not been proven in humans. The purpose of this study is to see how simvastatin affects a substance in the spinal fluid around the brain called beta-amyloid-42 which is thought to contribute to Alzheimer's disease. This study also evaluates whether simvastatin improves regional brain blood flow (on magnetic resonance imaging [MRI]), reduces inflammation, and improves cognitive function.
The ESPRIT study was a 9-month randomized, controlled clinical trial that randomized 100 middle-aged adults with a parental history of Alzheimer's disease. Participants were randomized to simvastatin 40 mg for one month then 80 mg daily or matching placebo tablets. Fifty of the ESPRIT subjects participated in the MRI sub-study.
Participants had the following data collected: fasting blood tests (baseline and months 3 and 9), medical history and medication questionnaires (each visit), study medication side effect review (all visits), lumbar puncture procedure (baseline and month 9), memory testing (baseline and months 3 and 9), and MRI (baseline and month 9 in 50 sub-study participants).
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Wisconsin
-
Madison, Wisconsin, United States, 53705
- University of Wisconsin
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 35 to 69
- Parent with Alzheimer's disease
Exclusion Criteria:
- Current use of cholesterol-lowering medication
- Active liver disease
- History of adverse reaction to statins
- Contraindication to lumbar puncture
- Elevated lab values (creatine kinase and creatinine)
- Use of medications known to interact with statins
- History of dementia
- Currently pregnant or planning to become pregnant
- Use of large quantities of grapefruit juice (more than 1 quart per day)
- Current involvement in another investigational drug study
- Contraindications to MRI (for MRI sub-study)
- Ethical contraindication to placebo (persons with high vascular risk)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: simvastatin
simvastatin 40 mg nightly for 1 month then 80 mg nightly for 8 months
|
40 mg tablet each night for one month, then 80 mg for 8 months
Other Names:
|
Placebo Comparator: Placebo
Matching placebo tablet nightly for 9 months
|
Matching tablet each night for 9 months
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in Cerebrospinal Fluid (CSF) Beta-amyloid-42
Time Frame: baseline and 9 months
|
baseline and 9 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Regional Cerebral Blood Flow on MRI
Time Frame: baseline and 9 months
|
Mean changes noted in posterior cingulate cortex
|
baseline and 9 months
|
Change in Inflammatory Markers
Time Frame: baseline and 9 months
|
Change noted in serum high-sensitivity c-reactive protein
|
baseline and 9 months
|
Changes in Cognitive Performance
Time Frame: Baseline and 9 months
|
Change in Hopkins Verbal Learning Test Delayed Recall The Hopkins Verbal Learning Test Delayed Recall score is the raw number of words recalled at Trial 4, adjusted for years of education and age. This is a 12-item word list test. |
Baseline and 9 months
|
Collaborators and Investigators
Publications and helpful links
General Publications
- Fassbender K, Simons M, Bergmann C, Stroick M, Lutjohann D, Keller P, Runz H, Kuhl S, Bertsch T, von Bergmann K, Hennerici M, Beyreuther K, Hartmann T. Simvastatin strongly reduces levels of Alzheimer's disease beta -amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5856-61. doi: 10.1073/pnas.081620098. Epub 2001 Apr 10.
- Wolozin B. A fluid connection: cholesterol and Abeta. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5371-3. doi: 10.1073/pnas.101123198. No abstract available.
- Johnson NA, Jahng GH, Weiner MW, Miller BL, Chui HC, Jagust WJ, Gorno-Tempini ML, Schuff N. Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience. Radiology. 2005 Mar;234(3):851-9. doi: 10.1148/radiol.2343040197.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Neurodegenerative Diseases
- Dementia
- Tauopathies
- Alzheimer Disease
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Simvastatin
Other Study ID Numbers
- IA0116
- 1K23AG026752-01 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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