Carotid Atherosclerosis Regression at Magnetic Resonance Assessment.

• Status: Completed
• Trial end date: 2005-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this randomized, double blind, placebo controlled pilot study is to determine if therapies aimed at lowering LDL cholesterol (HMGCoA reductase inhibitor - simvastatin) or increasing HDL cholesterol (Niaspan) will induce regression of carotid atherosclerotic plaque in vivo using MRI imaging techniques. MR plaque morphology at baseline will be compared to that after 6 and 12 months of therapy and changes in MR characteristics will be compared to changes in lipoprotein parameters and urinary isoprostanes. The effect of moderate LDL reduction, aggressive LDL reduction and the combination of aggressive LDL reduction and HDL elevation on MRI plaque characteristics will be compared by randomly assigning subjects (n=69) with carotid disease (>30% stenosis by ultrasound criteria) to one of three treatment arms;

1. Simvastatin 20 mg daily and placebo Niaspan (n=23)

2. Simvastatin 80 mg daily and placebo Niaspan (n=23)

3. Simvastatin 20 mg daily and active Niaspan (n=23) Treatment group 2 and 3 will have roughly equivalent LDL lowering because of the synergistic LDL lowering effect of the combination of simvastatin and Niaspan.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pennsylvania
• Collaborators: Kos Pharmaceuticals; Merck Sharp & Dohme Corp.; The Dana Foundation
• Treatments: Niacin; Simvastatin

Criteria

Inclusion Criteria:

• Age > 18 and < 90 years

• Capacity for giving written informed consent

• Carotid stenosis of > 30% by ultrasound criteria

• LDL cholesterol level of > 100mg/dl

• Systolic BP < 170 and diastolic BP < 100 under resting conditions

• Negative pregnancy test if female of child-bearing potential

Exclusion Criteria:

• Recent (< 3 months) history of stroke, transient ischemic attack, myocardial infarction, unstable angina or critical limb ischemia

• Contraindications to MRI (claustrophobia, presence of pacemakers, defibrillators, metal foreign bodies)

• History of side effect/adverse reaction on HMGCoA reductase inhibitor

• Niaspan or niacin

• Poorly controlled diabetes (HbA1c > 8%)

• History of myositis, liver disease or abnormal LFTs

• Need for combination therapy for the control of severe hyperlipidemia

• Abnormal LFT (> 2 fold upper limit normal)

• Active infection or malignancy