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

Coronary Artery Disease Clinical Trial

— CPC  

Official title:

Carotid Plaque Composition by Magnetic Resonance Imaging During Lipid Lowering Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00715273
• Other study ID #: STUDY00001165
• Secondary ID: R01HL063895-05A1
• Status: Completed
• Phase: Phase 4
• Start date: May 1, 2001
• Est. completion date: March 1, 2019

Study information

• Verified date: May 2022
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 217
• Est. completion date: March 1, 2019
• Est. primary completion date: December 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Carotid Artery Diseases
• Coronary Artery Disease

Intervention

Drug:
• Atorvastatin
10 to 80 mg of atorvastatin each day
• Niacin
2000 mg of niacin each day
• Colesevelam
3.8 g of colesevelam each day
• Placebo Niacin
Placebo niacin each day
• Placebo Colesevelam
Placebo colesevelam each day

Locations

Country	Name	City	State
United States	St. Luke's Idaho Cardiology	Boise	Idaho
United States	University of Southern California	Los Angeles	California
United States	University of Washington Coronary Atherosclerosis Research Lab	Seattle	Washington
United States	Yakima Heart Center	Yakima	Washington

Sponsors (6)

Lead Sponsor	Collaborator
University of Washington	Abbott, Daiichi Sankyo, Inc., National Heart, Lung, and Blood Institute (NHLBI), Pfizer, Upsher-Smith Laboratories

Country where clinical trial is conducted

United States, 

References & Publications (11)

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 Ju — View 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 J — View Citation

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/CIRCU — View Citation

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- — View 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. — View 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.j — View Citation

Phan BA, Muñoz 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 — View 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 — View Citation

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 — View 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 Composit — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized LRNC Volume Change in Carotid Plaque Composition, as Assessed by MRI	The primary endpoint of this study is carotid plaque lipid composition identified by MRI. The determination of plaque lipid content for each carotid artery will be performed using the automated interactive system. These measurements will be performed from the MRI scans at four time points blinded to time sequence of MRI examinations, patient treatment, lipid levels and clinical course.; Volume Measurements: Contours were placed around the lumen, outer-wall boundaries, and plaque features of carotid artery. (Arterial wall area) = (outer-wall area) - (lumen area). Volume calculated as: area x 2 mm (slice thickness). Tissue volume/wall volume x (100%) is presented as percentage. Annualized change presented mm^3/year (for volume) and as percentage change/year.	Measured at Years 1, 2, and 3
Primary	Annualized LRNC and Wall Volume Changes in Carotid Plaque Composition, as Assessed by MRI	The primary endpoint of this study is carotid plaque lipid composition identified by MRI. The determination of plaque lipid content for each carotid artery will be performed using the automated interactive system. These measurements will be performed from the MRI scans at four time points blinded to time sequence of MRI examinations, patient treatment, lipid levels and clinical course.; Volume Measurements: Contours were placed around the lumen, outer-wall boundaries, and plaque features of carotid artery. (Arterial wall area) = (outer-wall area) - (lumen area). Volume calculated as: area x 2 mm (slice thickness). Tissue volume/wall volume x (100%) is presented as percentage. Annualized change presented mm^3/year (for volume) and as percentage change/year.	Measured at Years 1, 2, and 3
Secondary	Composite of Cardiovascular Endpoints: Number of Participants With Cardiovascular Disease Death, Non-fatal Heart Attack, Stroke, and Worsening Ischemia Requiring Medical Interventions	Any cardiovascular events such as death from any cause, nonfatal myocardial infarction, stroke, and revascularization procedures (PCI or CABG) due to unstable ischemia will be recorded and verified.	Measured at Years 3, 4, and 5