Cerebral and Peripheral Perfusion Pilot Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the hypothesis that in middle-aged, asymptomatic, adult children of persons with Alzheimer's disease (AD), atorvastatin therapy will beneficially affect mechanisms thought to contribute to AD risk by improving blood flow in the brain, improving cerebral perfusion, increasing brain activity patterns, and improving blood vessel function.

Detailed Description
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Treatment with cholesterol-lowering medications, specifically statins, is associated with up to a 73% reduction in the prevalence of AD, suggesting a potentially promising role for statins in the prevention of AD. In order to better understand the mechanisms through which statins may possibly modify blood AD risk, this study evaluated whether administration of atorvastatin favorably altered blood flow in the brain (measured by magnetic resonance imaging (MRI)) and blood vessel function (measured by ultrasound). Participants attended 3 visits over the course of the 4-month study. At the initial visit, participants completed a short questionnaire about their past medical history and medication history. At the baseline visit, participants were randomized in a 1:1 ratio to receive atorvastatin 40 mg nightly vs. matching placebo. At baseline and follow-up visits, participants provided an update on medical problems and medications, reviewed any potential side effects, and had fasting blood tests collected for safety monitoring, including liver and muscle enzyme monitoring. In addition, all participants had MRI and ultrasound measures collected.

Official Title
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Impact of Atorvastatin on Cerebral Perfusion and Endothelial Function

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: atorvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (ages 40-65) children of parent with documented Alzheimer's disease Exclusion Criteria: Current use of cholesterol lowering medication History of liver disease History of adverse reaction to statin medications Elevated lab values (CK and creatinine) Use of medications that counteract with atorvastatin History of dementia Currently pregnant Use of large quantities of grapefruit juice (more than 1 quart/day) Current involvement in another investigational drug study Contraindications to MRI

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin<br>40mg Atorvastatin nightly for 4 months | Drug: atorvastatin<br>* 40mg daily for 4 months<br>* Other names: Lipitor;|
| Placebo Comparator: Placebo<br>matching placebo nightly for 4 months | Drug: Placebo<br>* Matching placebo daily for 4 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in regional cerebral blood flow (rCBF) | rCBF , a measure of cerebral perfusion, is the primary outcome. rCBF was measured by arterial spin-labeling magnetic resonance imaging and used to evaluate effects of atorvastatin vs placebo | Baseline and 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Endothelial function | Brachial artery reactivity was used to measure endothelial function | Baseline and 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebral blood flow