Carotid Plaque Characteristics by MRI in AIM-HIGH (Carotid MRI Substudy)

Coronary Artery Disease Clinical Trial

Official title:

Carotid Plaque Characteristics by MRI in AIM-HIGH

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01178320
• Other study ID #: 627
• Secondary ID: R01HL088214
• Status: Completed
• Phase: N/A
• First received: August 5, 2010
• Last updated: February 7, 2018
• Start date: March 2008
• Est. completion date: February 2015

Study information

• Verified date: February 2018
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Heart attacks and strokes caused by the unstable atherosclerotic plaques remain the leading cause of death in the United States. Unstable plaques often have more fat than stable plaques. This study will investigate if a treatment with LDL-lowering plus HDL-raising compared with LDL-lowering alone would more effectively reduce the plaque fat content assessed by magnetic resonance imaging (MRI), therefore, further reducing heart attacks and strokes.

Description:

Although studies have suggested that plaque morphology and composition are important determinants of plaque stability, our understanding on plaque tissue components is mainly from histological studies until recent development in MRI technique. A low level of HDL is associated with higher risk of cardiovascular events and increased amount of lipid content in the carotid plaques. Treatment with LDL-lowering plus HDL-raising compared with LDL-lowering alone more effectively protects against atherosclerosis progression. It is widely believed that HDL or its apolipoproteins mediate the removal of excess free cholesterol from peripheral cells and the cholesterol is delivered via either LDL or HDL to the liver for excretion into the bile. However, it has not been tested and approved in human atherosclerotic condition in vivo. The NIH/Abbott-funded multi-center AIM-HIGH trial is designed to compare the clinical efficacy of LDL-lowering alone with statin versus LDL-lowering plus HDL-raising with statin plus nicotinic acid combination therapy in patients with established vascular disease and high triglycerides and low HDL.

We propose to conduct a carotid MRI sub-study in 220 subjects enrolled in AIM-HIGH to investigate the important vascular biological mechanisms of HDL-raising therapy. Image collection will occur at 3 timepoints. The hypotheses and specific aims are:

• (1) To test the primary hypothesis that compared with LDL-lowering alone, intensive LDL-lowering plus HDL-raising therapy decreases the mean plaque lipid composition in carotid arteries assessed by MRI.

• (2) To test the hypothesis that compared with LDL-lowering alone, intensive LDL-lowering plus HDL-raising therapy decreases the plaque burden including volume and wall thickness.

• (3) To test the hypothesis that increased plaque lipid composition or vessel wall thickness by MRI is associated with increased risk of cardiovascular events.

• (4)To test a hypothesis that LDL-lowering plus HDL-raising, compared to LDL-lowering alone, will promote more rapid plaque lipid depletion. And determine the time-course of atherosclerotic plaque lipid depletion during lipid therapy.

• (5) To examine the association of clinical risk factors, lipids, lipoprotein heterogeneity, inflammatory markers and carotid plaque characteristics.

This MRI sub-study offers a unique opportunity to investigate the effectiveness of LDL-lowering plus HDL-raising therapy on human atherosclerotic plaque in vivo, to examine the association of plaque characteristics both lipid composition and volume assessed by MRI and cardiovascular outcome, and to gain novel insights in our understanding of atherosclerotic plaque pathology and the mechanisms of intensive lipid management in preventing cardiovascular events.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: February 2015
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

Inclusion Criteria:

• Eligible for main AIM-HIGH study (NCT00120289)

• Medically able to undergo MRI procedure

• Willing to provide informed consent for participation in this substudy

Exclusion Criteria:

• Uses pacemaker or has metallic implants

• History of bilateral carotid endarterectomy

• Glomerular filtration rate less than 60 mL/min/1.73 m^2

Related Conditions & MeSH terms

• Atherosclerosis
• Carotid Artery Diseases
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Simvastatin, simvastatin plus extended-release niacin
Participants will be enrolled in this substudy only if they are candidates for the main AIM-HIGH study (NCT00120289). Participants will be randomly assigned to simvastatin or simvastatin plus niacin as a part of the main AIM-HIGH protocol, and adjustments in simvastatin and/or niacin doses will be made as per the protocol for the main AIM-HIGH study.

Locations

Country	Name	City	State
Canada	Heart Health Institute	Calgary	Alberta
Canada	University of Calgary	Calgary	Alberta
Canada	University of Western Ontario	London	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Duke University	Durham	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Kelsey Research Foundation	Houston	Texas
United States	Methodist Hospital	Houston	Texas
United States	Long Beach VA Medical Center	Long Beach	California
United States	University of Southern California	Los Angeles	California
United States	Philadelphia VA Medical Center	Philadelphia	Pennsylvania
United States	Cardiovascular Consultants	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota
United States	Harborview Medical Center	Seattle	Washington
United States	Puget Sound VA Medical Center, Seattle Campus	Seattle	Washington
United States	University of Washington	Seattle	Washington
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (4)

Chen H, Sun J, Kerwin WS, Balu N, Neradilek MB, Hippe DS, Isquith D, Xue Y, Yamada K, Peck S, Yuan C, O'Brien KD, Zhao XQ. Scan-rescan reproducibility of quantitative assessment of inflammatory carotid atherosclerotic plaque using dynamic contrast-enhance — View Citation

Hippe DS, Phan BAP, Sun J, Isquith DA, O'Brien K, Crouse JR, Anderson T, Huston J, Marcovina SM, Hatsukami TS, Yuan C, Zhao XQ. Lp(a) (Lipoprotein(a)) Levels Predict Progression of Carotid Atherosclerosis in Subjects With Atherosclerotic Cardiovascular Di — View Citation

Sun J, Zhao XQ, Balu N, Hippe DS, Hatsukami TS, Isquith DA, Yamada K, Neradilek MB, Cantón G, Xue Y, Fleg JL, Desvigne-Nickens P, Klimas MT, Padley RJ, Vassileva MT, Wyman BT, Yuan C. Carotid magnetic resonance imaging for monitoring atherosclerotic plaqu — View Citation

Zhao XQ, Hatsukami TS, Hippe DS, Sun J, Balu N, Isquith DA, Crouse JR 3rd, Anderson T, Huston J 3rd, Polissar N, O'Brien K, Yuan C; AIM-HIGH Carotid MRI Sub-study Investigators. Clinical factors associated with high-risk carotid plaque features as assesse — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean plaque lipid composition in carotid arteries assessed by MR	To test the primary hypothesis that compared with LDL-lowering alone, intensive LDL-lowering plus HDL-raising therapy decreases the mean plaque lipid composition in carotid arteries assessed by MRI.	Through 24Months post AIM-HIGH Randomization
Secondary	Additional plaque characteristics as assessed by MRI	To test the additional hypotheses regarding plaque burden, plaque lipid depletion time course, association with cardiovascular event risk and lipid characteristics.	Through 24Months post AIM-HIGH Randomization