Clinical trial NCT00715273: Evaluate Carotid Artery Plaque Composition by Magnetic Resonance Imaging in People Receiving Cholesterol Medication
Official title: Carotid Plaque Composition by Magnetic Resonance Imaging During Lipid Lowering Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Carotid Artery Diseases
Atherosclerosis
Keywords: Magnetic Resonance Imaging
Atherosclerotic Plaque
Lipid Lowering Therapy
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Pfizer
name: Abbott
name: Daiichi Sankyo
name: Upsher-Smith Laboratories
First posted: 2008-07-15
Enrollment: 217
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Atherosclerosis is a condition that occurs when fatty deposits build up along the inner walls of arteries. This study will examine the effectiveness of a combination of cholesterol-lowering medications at decreasing the fat content of atherosclerotic deposits in people who have coronary artery disease or carotid artery disease.

Detailed description: Atherosclerosis is a condition in which deposits of fat, cholesterol, and other substances build up along the inner walls of arteries; these deposits are known as plaque. People with atherosclerosis are at risk of developing coronary artery disease, in which plaque build-up occurs in the arteries that supply blood to the heart, and carotid artery disease, in which plaque build-up occurs in the arteries that deliver blood through the neck to the brain. These conditions can lead to blood clots, heart attack, and stroke. Research has shown that people who have more fat content in atherosclerotic plaque may have a higher risk of experiencing a heart attack or stroke. Treatments for atherosclerosis include lifestyle changes, medicines, and medical procedures or surgery. There are several medications that can aid people in controlling their cholesterol levels, including atorvastatin, a medication that inhibits the production of cholesterol; niacin, a B-complex vitamin that can reduce cholesterol levels in combination with dietary changes; and colesevelam, a medication that inhibits fat absorption. Using magnetic resonance imaging (MRI), this study will evaluate whether these medications, alone or in combination, can decrease the fat content of atherosclerotic plaques within the carotid arteries of people with coronary artery disease and carotid artery disease.

This study will enroll people with coronary artery disease or carotid artery disease. Participants will be randomly assigned to one of the following 40-month treatment groups:

* Group 1 participants will receive atorvastatin, placebo niacin, and placebo colesevelam each day.
* Group 2 participants will receive atorvastatin, niacin, and placebo colesevelam each day.
* Group 3 participants will receive atorvastatin, niacin, and colesevelam each day.

At a baseline study visit, participants will undergo a blood collection and will receive dietary counseling that will focus on lowering cholesterol levels. They will also undergo an MRI scan of their carotid arteries. For the next 4 months, participants will attend monthly study visits for repeat blood collection and dietary counseling; for the subsequent 36 months, participants will attend study visits every other month. Repeat carotid artery MRI scans will occur at Months 12, 24, and 36. At three different times during the study, researchers will ask participants to record their food consumption for 3 consecutive days.

Eligibility criteria: Inclusion Criteria:

* Clinically established coronary artery disease or carotid artery disease with greater than 15% stenosis by ultrasound
* Family history of cardiovascular disease
* Apolipoprotein B level greater than or equal to 120 mg/dL (LDL level should be between 100 and 190 mg/dL without medication)
* Has been undergoing lipid therapy for no more than 12 months before study entry
* Medically stable
* Medically able to undergo MRI procedure

Exclusion Criteria:

* Uses pacemaker or has metallic implants
* Has immediate plans for carotid endarterectomy
* History of alcohol or drug abuse
* Active liver disease or liver dysfunction, defined by elevations in alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels greater than 1.5 times the upper limit of normal
* Serum creatine kinase (CK) level greater than 3 times the upper limit of normal before study entry
* Serum creatinine level greater than 2.5 times the upper limit of normal
* Diabetes, with a fasting glucose level greater than 150 mg/dL or hemoglobin A1c (HbA1c) level greater than 8% before study entry
* Uncontrolled high blood pressure, defined as average resting systolic blood pressure greater than 200 mm Hg or average resting diastolic blood pressure greater than 95 mm Hg

Primary outcomes:
measure: Annualized LRNC Volume Change in Carotid Plaque Composition, as Assessed by MRI
timeFrame: Measured at Years 1, 2, and 3
measure: Annualized LRNC and Wall Volume Changes in Carotid Plaque Composition, as Assessed by MRI
timeFrame: Measured at Years 1, 2, and 3
Secondary outcomes:
measure: Composite of Cardiovascular Endpoints: Number of Participants With Cardiovascular Disease Death, Non-fatal Heart Attack, Stroke, and Worsening Ischemia Requiring Medical Interventions
timeFrame: Measured at Years 3, 4, and 5
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Boise
country: United States
facility: St. Luke's Idaho Cardiology
state: Idaho
city: Seattle
country: United States
facility: University of Washington Coronary Atherosclerosis Research Lab
state: Washington
city: Yakima
country: United States
facility: Yakima Heart Center
state: Washington
Study officials:
affiliation: University of Washington
name: Xue-Qiao Zhao, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhao XQ, Phan BA, Chu B, Bray F, Moore AB, Polissar NL, Dodge JT Jr, Lee CD, Hatsukami TS, Yuan C. Testing the hypothesis of atherosclerotic plaque lipid depletion during lipid therapy by magnetic resonance imaging: study design of Carotid Plaque Composition Study. Am Heart J. 2007 Aug;154(2):239-46. doi: 10.1016/j.ahj.2007.04.035.
citation: Moore A, Phan BA, Challender C, Williamson J, Marcovina S, Zhao XQ. Effects of adding extended-release niacin and colesevelam to statin therapy on lipid levels in subjects with atherosclerotic disease. J Clin Lipidol. 2007 Dec;1(6):620-5. doi: 10.1016/j.jacl.2007.09.001. Epub 2007 Sep 15.
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citation: Ronsein GE, Hutchins PM, Isquith D, Vaisar T, Zhao XQ, Heinecke JW. Niacin Therapy Increases High-Density Lipoprotein Particles and Total Cholesterol Efflux Capacity But Not ABCA1-Specific Cholesterol Efflux in Statin-Treated Subjects. Arterioscler Thromb Vasc Biol. 2016 Feb;36(2):404-11. doi: 10.1161/ATVBAHA.115.306268. Epub 2015 Dec 17.
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citation: Dong L, Kerwin WS, Chen H, Chu B, Underhill HR, Neradilek MB, Hatsukami TS, Yuan C, Zhao XQ. Carotid artery atherosclerosis: effect of intensive lipid therapy on the vasa vasorum--evaluation by using dynamic contrast-enhanced MR imaging. Radiology. 2011 Jul;260(1):224-31. doi: 10.1148/radiol.11101264. Epub 2011 Apr 14.
citation: Kerwin WS, Zhao X, Yuan C, Hatsukami TS, Maravilla KR, Underhill HR, Zhao X. Contrast-enhanced MRI of carotid atherosclerosis: dependence on contrast agent. J Magn Reson Imaging. 2009 Jul;30(1):35-40. doi: 10.1002/jmri.21826.
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