We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluating Simvastatin's Potential Role in Therapy (ESPRIT)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00486044
First Posted: June 13, 2007
Last Update Posted: November 5, 2015
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.
Collaborators:
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
  Purpose
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
Intervention Model: Parallel Assignment
Masking: Triple (Participant, 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 ]

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

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

  • 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.



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).

  Eligibility

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.


Ages Eligible for Study:   35 Years to 69 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT00486044


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

Additional Information:
Publications:
Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT00486044     History of Changes
Other Study ID Numbers: IA0116
1K23AG026752-01 ( U.S. NIH Grant/Contract )
First Submitted: June 12, 2007
First Posted: June 13, 2007
Results First Submitted: November 16, 2012
Results First Posted: November 5, 2015
Last Update Posted: November 5, 2015
Last Verified: March 2014

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

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors