Evaluating Simvastatin's Potential Role in Therapy (ESPRIT)

University of Wisconsin (UW)

Status and phase: Completed; Phase 2

Conditions: Alzheimer Disease

Treatments: Drug: Placebo; Drug: Simvastatin

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00486044

IA0116

1K23AG026752-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 103 patients

Sex: All

Ages: 35 to 69 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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103 participants in 2 patient groups, including a placebo group

simvastatin

Experimental group

Description:

simvastatin 40 mg nightly for 1 month then 80 mg nightly for 8 months

Treatment:

Drug: Simvastatin

Placebo

Placebo Comparator group

Description:

Matching placebo tablet nightly for 9 months

Treatment:

Drug: Placebo