Evaluating Simvastatin's Potential Role in Therapy

Alzheimer Disease Clinical Trial

— ESPRIT  

Official title:

Effect of Statins on Pathobiology of Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00486044
• Other study ID #: IA0116
• Secondary ID: 1K23AG026752-01
• Status: Completed
• Phase: Phase 2
• Start date: February 2005
• Est. completion date: June 2009

Study information

• Verified date: February 2019
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 35 Years to 69 Years

Eligibility

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)

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• Simvastatin
40 mg tablet each night for one month, then 80 mg for 8 months
• Placebo
Matching tablet each night for 9 months

Locations

Country	Name	City	State
United States	University of Wisconsin	Madison	Wisconsin

Sponsors (8)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	American Federation for Aging Research, Merck Sharp & Dohme Corp., National Institute on Aging (NIA), Paul Beeson Faculty Scholars Program, Starr Foundation, The Atlantic Philanthropies, The John A. Hartford Foundation

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. Epub 2001 Apr 10. — View Citation

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. — View Citation

Wolozin B. A fluid connection: cholesterol and Abeta. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5371-3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Cerebrospinal Fluid (CSF) Beta-amyloid-42		baseline and 9 months
Secondary	Changes in Regional Cerebral Blood Flow on MRI	Mean changes noted in posterior cingulate cortex	baseline and 9 months
Secondary	Change in Inflammatory Markers	Change noted in serum high-sensitivity c-reactive protein	baseline and 9 months
Secondary	Changes in Cognitive Performance	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

External Links

•   Wisconsin Alzheimer's Disease Research Center