Evaluating Simvastatin's Potential Role in Therapy (ESPRIT)

February 14, 2019 updated by: University of Wisconsin, Madison

Effect of Statins on Pathobiology of Alzheimer's Disease

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.

Study Overview

Status

Completed

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

Interventional

Enrollment (Actual)

103

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • University of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 69 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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:
  • Zocor
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

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2005

Primary Completion (Actual)

June 1, 2009

Study Completion (Actual)

June 1, 2009

Study Registration Dates

First Submitted

June 12, 2007

First Submitted That Met QC Criteria

June 12, 2007

First Posted (Estimate)

June 13, 2007

Study Record Updates

Last Update Posted (Actual)

March 5, 2019

Last Update Submitted That Met QC Criteria

February 14, 2019

Last Verified

February 1, 2019

More Information

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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