Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

Evaluating Simvastatin's Potential Role in Therapy (ESPRIT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00486044
Recruitment Status : Completed
First Posted : June 13, 2007
Results First Posted : November 5, 2015
Last Update Posted : March 5, 2019
National Institute on Aging (NIA)
Paul Beeson Faculty Scholars Program
The John A. Hartford Foundation
The Atlantic Philanthropies
Starr Foundation
American Federation for Aging Research
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
University of Wisconsin, Madison

Brief Summary:
The purpose of this study is to see how simvastatin, a cholesterol-lowering drug, affects processes related to the development of Alzheimer's disease, including: 1) levels of a substance called beta-amyloid-42 found in the spinal fluid surrounding the brain, 2) blood flow in the brain, 3) inflammation in the brain, and 4) cognitive function.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: Simvastatin Drug: Placebo Phase 2

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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 103 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Effect of Statins on Pathobiology of Alzheimer's Disease
Study Start Date : February 2005
Actual Primary Completion Date : June 2009
Actual Study Completion Date : June 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Simvastatin

Arm Intervention/treatment
Experimental: simvastatin
simvastatin 40 mg nightly for 1 month then 80 mg nightly for 8 months
Drug: Simvastatin
40 mg tablet each night for one month, then 80 mg for 8 months
Other Name: Zocor

Placebo Comparator: Placebo
Matching placebo tablet nightly for 9 months
Drug: Placebo
Matching tablet each night for 9 months

Primary Outcome Measures :
  1. Change in Cerebrospinal Fluid (CSF) Beta-amyloid-42 [ Time Frame: baseline and 9 months ]

Secondary Outcome Measures :
  1. Changes in Regional Cerebral Blood Flow on MRI [ Time Frame: baseline and 9 months ]
    Mean changes noted in posterior cingulate cortex

  2. Change in Inflammatory Markers [ Time Frame: baseline and 9 months ]
    Change noted in serum high-sensitivity c-reactive protein

  3. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   35 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00486044

Layout table for location information
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
University of Wisconsin, Madison
National Institute on Aging (NIA)
Paul Beeson Faculty Scholars Program
The John A. Hartford Foundation
The Atlantic Philanthropies
Starr Foundation
American Federation for Aging Research
Merck Sharp & Dohme LLC
Layout table for investigator information
Principal Investigator: Cynthia M. Carlsson, MD, MS University of Wisconsin, Madison
Additional Information:
Layout table for additonal information
Responsible Party: University of Wisconsin, Madison Identifier: NCT00486044    
Other Study ID Numbers: IA0116
1K23AG026752-01 ( U.S. NIH Grant/Contract )
First Posted: June 13, 2007    Key Record Dates
Results First Posted: November 5, 2015
Last Update Posted: March 5, 2019
Last Verified: February 2019
Keywords provided by University of Wisconsin, Madison:
amyloid protein
cerebrospinal fluid
cerebrovascular circulation
magnetic resonance imaging
prevention & control
Additional relevant MeSH terms:
Layout table for MeSH terms
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors