Evaluating Simvastatin's Potential Role in Therapy (ESPRIT)

This study has been completed.
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 Corp.
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
First received: June 12, 2007
Last updated: October 1, 2015
Last verified: March 2014
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 Intervention Phase
Alzheimer Disease
Drug: Simvastatin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Effect of Statins on Pathobiology of Alzheimer's Disease

Resource links provided by NLM:

Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Change in Cerebrospinal Fluid (CSF) Beta-amyloid-42 [ Time Frame: baseline and 9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in Regional Cerebral Blood Flow on MRI [ Time Frame: baseline and 9 months ] [ Designated as safety issue: No ]
    Mean changes noted in posterior cingulate cortex

  • Change in Inflammatory Markers [ Time Frame: baseline and 9 months ] [ Designated as safety issue: No ]
    Change noted in serum high-sensitivity c-reactive protein

  • Changes in Cognitive Performance [ Time Frame: Baseline and 9 months ] [ Designated as safety issue: No ]

    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.

Enrollment: 103
Study Start Date: February 2005
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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).


Ages Eligible for Study:   35 Years to 69 Years
Genders Eligible for Study:   Both
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)
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00486044

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 Corp.
Principal Investigator: Cynthia M. Carlsson, MD, MS University of Wisconsin, Madison
  More Information

Additional Information:
Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT00486044     History of Changes
Other Study ID Numbers: IA0116, 1K23AG026752-01
Study First Received: June 12, 2007
Results First Received: November 16, 2012
Last Updated: October 1, 2015
Health Authority: United States: Federal Government

Keywords provided by University of Wisconsin, Madison:
amyloid protein
cerebrospinal fluid
cerebrovascular circulation
magnetic resonance imaging
prevention & control

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Anticholesteremic Agents
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2015