Effect of Short Term Atorvastatin Treatment,80mg/Day on Early Regression of Carotid Artery Atherosclerotic Lesions

Study Overview
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Brief Summary
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Atherosclerosis is a disease in which the blood vessels become blocked by plaques (consisting of fat, calcification, and fibrous tissue), reducing blood flow to vital organs and tissues.Blockage of the carotid arteries in the neck is a major cause of stroke. One way of treating carotid atherosclerosis is with cholesterol-lowering drugs called statins. Statins have been shown to reduce the risk of coronary heart disease by 24-40% and risk pf stroke by 11-30%.The purpose of this study is to determine if short term treatment with atorvastatin causes early favorable changes in the plaques that block blood flow through the carotid arteries. These changes can be assessed 1) by taking pictures of the carotid arteries with MRI and Ultrasound before and after statin treatment, and 2) by special studies of the plaques removed from the carotid arteries by surgery.

Detailed Description
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Candidates for bilateral carotid endarterectomy (CEA) who meet study criteria will provide informed consent before their randomization. Before the first CEA, the patient will have MRI, US, and EBCT exams of both carotids. The most occlusive plaque will be resected at the first CEA. The patient will then receive atorvastatin 80 mg/day for 3 months. Then the second CEA will be performed. Six weeks after the second CEA, the patient will have another MRI, US, and EBCT exam and at 6, 12, and 18 months thereafter. This protocol will allow comparison of the characteristics of the plaque that has been exposed to drug vs the plaque that has not been exposed. It will also allow monitoring the effect of drug on restenosis after surgery.

Official Title
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Phase 3 Study of Atorvastatin Effects on Carotid Atherosclerosis

Conditions
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Atherosclerosis

Intervention / Treatment
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* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women >18 yrs old Expected to have an endarterectomy on each carotid artery No contraindications for atorvastatin Stable cardiovascular health Lipid lowering treatment less than 6 mo duration Diabetic included if diabetes is controlled Patient is not claustrophobic Patient has evaluable carotid plaques. Exclusion Criteria: Patient has had previous carotid endarterectomy,stenting, or other procedure Unstable cardiovascular status Hypersensitivity to statin therapy Neck anatomy preventing acquiring bilateral evaluable plaques Weight over 285 lbs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: A<br>An untreated carotid plaque will be obtained at the first endarterectomy. Atorvastatin 80mg will be administered for 3 months. The contralateral (treated) plaque will be obtained at the second endarterectomy. Hence, each patient will be his/her own control | Drug: Atorvastatin<br>* Atorvastatin 80 mg tablet/day for 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in carotid plaque composition as assessed by MRI and histology |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes content of cells, proteins and genes in carotid plaque |  | 3 months | 
| Changes in content of selected proteins and their encoding genes in carotid plaques |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atherogenesis, Atheroma, Arteriosclerosis