Evaluate Carotid Artery Plaque Composition by Magnetic Resonance Imaging in People Receiving Cholesterol Medication

NCT ID: NCT00715273

Last Updated: 2022-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 217 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-05-01
• Study Completion Date: 2019-03-01

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.

Conditions

Coronary Artery Disease; Carotid Artery Diseases; Atherosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

1 - single therapy group

Participants will receive atorvastatin, placebo niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the single therapy group.

Group Type: ACTIVE_COMPARATOR

Atorvastatin

Intervention Type: DRUG

10 to 80 mg of atorvastatin each day

Placebo Niacin

Intervention Type: DRUG

Placebo niacin each day

Placebo Colesevelam

Intervention Type: DRUG

Placebo colesevelam each day

2 - double therapy group

Participants will receive atorvastatin, niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the double therapy group.

Group Type: EXPERIMENTAL

Atorvastatin

Intervention Type: DRUG

10 to 80 mg of atorvastatin each day

Niacin

Intervention Type: DRUG

2000 mg of niacin each day

Placebo Colesevelam

Intervention Type: DRUG

Placebo colesevelam each day

3 - triple therapy group

Participants will receive atorvastatin, niacin, and colesevelam. The treatment target for LDL-C will be ≤60 mg/dl for the triple therapy group

Group Type: EXPERIMENTAL

Atorvastatin

Intervention Type: DRUG

10 to 80 mg of atorvastatin each day

Niacin

Intervention Type: DRUG

2000 mg of niacin each day

Colesevelam

Intervention Type: DRUG

3.8 g of colesevelam each day

Interventions

Atorvastatin

10 to 80 mg of atorvastatin each day

Intervention Type: DRUG

Niacin

2000 mg of niacin each day

Intervention Type: DRUG

Colesevelam

3.8 g of colesevelam each day

Intervention Type: DRUG

Placebo Niacin

Placebo niacin each day

Intervention Type: DRUG

Placebo Colesevelam

Placebo colesevelam each day

Intervention Type: DRUG

Other Intervention Names

Lipitor; Niaspan; Slo-niacin; WelChol

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Pfizer

INDUSTRY

Sponsor Role: collaborator

Abbott

INDUSTRY

Sponsor Role: collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role: collaborator

Upsher-Smith Laboratories

INDUSTRY

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Xue-Qiao Zhao

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xue-Qiao Zhao, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

University of Southern California

Los Angeles, California, United States

St. Luke's Idaho Cardiology

Boise, Idaho, United States

University of Washington Coronary Atherosclerosis Research Lab

Seattle, Washington, United States

Yakima Heart Center

Yakima, Washington, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 17643572 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21291704 (View on PubMed)

Green PS, Vaisar T, Pennathur S, Kulstad JJ, Moore AB, Marcovina S, Brunzell J, Knopp RH, Zhao XQ, Heinecke JW. Combined statin and niacin therapy remodels the high-density lipoprotein proteome. Circulation. 2008 Sep 16;118(12):1259-67. doi: 10.1161/CIRCULATIONAHA.108.770669. Epub 2008 Sep 2.

Reference Type: RESULT

PMID: 18765395 (View on PubMed)

Phan BA, Munoz L, Shadzi P, Isquith D, Triller M, Brown BG, Zhao XQ. Effects of niacin on glucose levels, coronary stenosis progression, and clinical events in subjects with normal baseline glucose levels (<100 mg/dl): a combined analysis of the Familial Atherosclerosis Treatment Study (FATS), HDL-Atherosclerosis Treatment Study (HATS), Armed Forces Regression Study (AFREGS), and Carotid Plaque Composition by MRI during lipid-lowering (CPC) study. Am J Cardiol. 2013 Feb 1;111(3):352-5. doi: 10.1016/j.amjcard.2012.09.034. Epub 2012 Nov 17.

Reference Type: RESULT

PMID: 23168285 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26681752 (View on PubMed)

Zhao XQ, Yuan C, Shah PK. Imaging to Assess the Effect of Anti-Inflammatory Therapy in Aortic and Carotid Atherosclerosis. J Am Coll Cardiol. 2016 Oct 18;68(16):1781-1784. doi: 10.1016/j.jacc.2016.08.011. No abstract available.

Reference Type: RESULT

PMID: 27737745 (View on PubMed)

Chu MP, Many G, Isquith DA, McKeeth S, Williamson J, Neradilek MB, Colletti P, Zhao XQ. Metabolic and inflammatory risk reduction in response to lipid-lowering and lifestyle modification in the medically underserved individuals. Am J Prev Cardiol. 2021 Jul 31;7:100227. doi: 10.1016/j.ajpc.2021.100227. eCollection 2021 Sep.

Reference Type: RESULT

PMID: 34401861 (View on PubMed)

Han T, Paramsothy P, Hong J, Isquith D, Xu D, Bai H, Neradilek M, Gill E, Zhao XQ. High-resolution MRI assessed carotid atherosclerotic plaque characteristics comparing men and women with elevated ApoB levels. Int J Cardiovasc Imaging. 2020 Mar;36(3):481-489. doi: 10.1007/s10554-019-01600-1. Epub 2020 Feb 4.

Reference Type: RESULT

PMID: 32020410 (View on PubMed)

Zhao XQ, Dong L, Hatsukami T, Phan BA, Chu B, Moore A, Lane T, Neradilek MB, Polissar N, Monick D, Lee C, Underhill H, Yuan C. MR imaging of carotid plaque composition during lipid-lowering therapy a prospective assessment of effect and time course. JACC Cardiovasc Imaging. 2011 Sep;4(9):977-86. doi: 10.1016/j.jcmg.2011.06.013.

Reference Type: RESULT

PMID: 21920335 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21493792 (View on PubMed)

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.

Reference Type: RESULT

PMID: 19557844 (View on PubMed)

Ronsein GE, Vaisar T, Davidson WS, Bornfeldt KE, Probstfield JL, O'Brien KD, Zhao XQ, Heinecke JW. Niacin Increases Atherogenic Proteins in High-Density Lipoprotein of Statin-Treated Subjects. Arterioscler Thromb Vasc Biol. 2021 Aug;41(8):2330-2341. doi: 10.1161/ATVBAHA.121.316278. Epub 2021 Jun 17.

Reference Type: DERIVED

PMID: 34134520 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01HL063895-05A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00001165

Identifier Type: -

Identifier Source: org_study_id