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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Xue-Qiao Zhao, University of Washington
ClinicalTrials.gov Identifier:
NCT01178320
First received: August 5, 2010
Last updated: May 19, 2014
Last verified: May 2014

August 5, 2010
May 19, 2014
March 2008
April 2013   (final data collection date for primary outcome measure)
Mean plaque lipid composition in carotid arteries assessed by MR [ Time Frame: Through 24Months post AIM-HIGH Randomization ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01178320 on ClinicalTrials.gov Archive Site
Additional plaque characteristics as assessed by MRI [ Time Frame: Through 24Months post AIM-HIGH Randomization ] [ Designated as safety issue: No ]
To test the additional hypotheses regarding plaque burden, plaque lipid depletion time course, association with cardiovascular event risk and lipid characteristics.
Same as current
Not Provided
Not Provided
 
Carotid Plaque Characteristics by MRI in AIM-HIGH (Carotid MRI Substudy)
Carotid Plaque Characteristics by MRI in AIM-HIGH

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.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Not Provided
Probability Sample

Participants in the main AIM-HIGH study (NCT00120289)

  • Coronary Artery Disease
  • Carotid Artery Diseases
  • Atherosclerosis
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.
Other Names:
  • simvastatin
  • Zocor
  • niacin
  • Niaspan
  • Simvastatin
    Participants in the main AIM-HIGH study who are receiving simvastatin.
    Intervention: Drug: Simvastatin, simvastatin plus extended-release niacin
  • Simvastatin and Extended-Release Niacin
    Participants in the main AIM-HIGH study who are receiving simvastatin and extended-release niacin.
    Intervention: Drug: Simvastatin, simvastatin plus extended-release niacin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
230
February 2015
April 2013   (final data collection date for primary outcome measure)

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
Both
45 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01178320
627, R01HL088214
Yes
Xue-Qiao Zhao, University of Washington
University of Washington
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Xue-Qiao Zhao, MD University of Washington
University of Washington
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP