Evaluating Simvastatin's Potential Role in Therapy

University of Wisconsin, Madison103 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

103

Conditions

Alzheimer Disease

Interventions

SimvastatinDRUG

40 mg tablet each night for one month, then 80 mg for 8 months

PlaceboDRUG

Matching tablet each night for 9 months

Eligibility

Sex: ALLMin age: 35 YearsMax age: 69 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Locations (1)

University of Wisconsin

Madison, Wisconsin, United States

Outcomes

Primary Outcomes

Change in Cerebrospinal Fluid (CSF) Beta-amyloid-42

Time frame: baseline and 9 months

Secondary Outcomes

Changes in Regional Cerebral Blood Flow on MRI

Mean changes noted in posterior cingulate cortex

Time frame: baseline and 9 months

Change in Inflammatory Markers

Change noted in serum high-sensitivity c-reactive protein

Time frame: baseline and 9 months

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.

Time frame: Baseline and 9 months

Data from ClinicalTrials.gov

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