Plaque Inflammation and Dysfunctional HDL Cholesterol in Participants Receiving Niacin and Statins in the AIM-HIGH Study (The HDL Proteomics Study) - Full Text View

Purpose

Coronary heart disease (CHD) is a serious health concern that affects millions of people in the United States. It is usually caused by atherosclerosis—a condition that occurs when fatty material and plaque build up on the walls of the arteries that supply blood and oxygen to the heart, causing the arteries to narrow. As the arteries narrow, blood flow to the heart can slow down or stop, which can cause chest pain, shortness of breath, heart attack, or heart failure. Another component of CHD events involves inflammatory changes that result in structural breakdown of atherosclerotic plaques. Adding niacin to statin medications may be an effective way to block inflammation in the atherosclerotic plaques. This study will examine magnetic resonance imaging (MRI) images and blood samples of participants in the AIM-HIGH study who are taking niacin plus statins or statins alone to determine the effect of these medications on inflammation in atherosclerotic plaques.

Condition	Intervention
Cardiovascular Diseases Heart Diseases Coronary Disease Atherosclerosis Myocardial Infarction	Drug: Simvastatin, simvastatin plus extended-release niacin


Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Prospective
Official Title:	Plaque Inflammation and Dysfunctional HDL in AIM-HIGH

Resource links provided by NLM:

MedlinePlus related topics: Atherosclerosis Heart Attack Heart Diseases Statins

Drug Information available for: Niacin Niacinamide Simvastatin

U.S. FDA Resources

Further study details as provided by University of Washington:

Primary Outcome Measures:

Change in HDL oxidation and proteomics [ Time Frame: Measured at Year 2 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Comparison of HDL oxidation and proteomics changes between participants receiving statins versus participants receiving statins plus niacin [ Time Frame: Measured at Year 2 ] [ Designated as safety issue: No ]
Comparison of change in Ktrans MRI marker of plaque inflammation between participants receiving statins versus participants receiving statins plus niacin [ Time Frame: Measured at Year 2 ] [ Designated as safety issue: No ]
Comparison of changes in HDL oxidation and proteomics with change in Ktrans MRI marker of plaque inflammation [ Time Frame: Measured at Year 2 ] [ Designated as safety issue: No ]
Change in Ktrans MRI marker of plaque inflammation [ Time Frame: Measured at Year 2 ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples Without DNA

Plasma for HDL isolation


Enrollment:	324
Study Start Date:	May 2008
Study Completion Date:	September 2011
Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Simvastatin Participants in the main AIM-HIGH study who are receiving simvastatin.	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.
Simvastatin and Extended-Release Niacin Participants in the main AIM-HIGH study who are receiving simvastatin and extended-release niacin.	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.

Groups/Cohorts

Assigned Interventions

Simvastatin

Participants in the main AIM-HIGH study who are receiving simvastatin.

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.

Simvastatin and Extended-Release Niacin

Participants in the main AIM-HIGH study who are receiving simvastatin and extended-release niacin.

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.

Detailed Description:

CHD is the leading cause of death in the United States. Preliminary research has shown that CHD is associated with oxidative and inflammatory changes in high-density lipoprotein (HDL) cholesterol, which is considered the "good" cholesterol. The inflammatory changes can impair HDL cholesterol's normal function, which is to remove excess cholesterol from the arteries and thereby slow the build-up of atherosclerotic plaque. Statins are cholesterol-lowering medications that are used to treat people with CHD. Taking niacin, a type of B vitamin, in combination with statins may stabilize atherosclerotic plaques better than statins alone, but more research is needed to examine how niacin may do this. By improving the ability of HDL cholesterol to repair inflammatory damage to atherosclerotic plaques, niacin may assist in preventing the inflammation that leads to plaque breakdown.

The AIM-HIGH study (NCT00120289) is examining the use of niacin plus statins in people with vascular disease. Participants in the AIM-HIGH study are randomly assigned to receive either niacin plus simvastain, which is a type of statin medication, or simvastain alone. The purpose of this substudy is to determine whether niacin in combination with statins reduces atherosclerotic plaque inflammation and dysfunctional HDL cholesterol more than statins alone. The substudy will enroll participants who are participating in the AIM-HIGH study. At the AIM-HIGH baseline and Year 2 study visits, study researchers for this substudy will collect an additional blood sample from participants to examine the changes in HDL oxidation levels and protein composition at both time points. Study researchers will also analyze participants' MRI scans to examine changes in plaque inflammation during the study period; these MRI scans will be completed as part of another AIM-HIGH substudy, conducted by Dr. Xue-Qiao Zhao. There will be no additional study procedures or visits for participants in this substudy.

Eligibility


Ages Eligible for Study:	45 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

Participants in the main AIM-HIGH study (NCT00120289)

Criteria

Inclusion Criteria:

Eligible for main AIM-HIGH study (NCT00120289)
Willing to provide informed consent for participation in this substudy

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00880178

Show 29 Study Locations

Sponsors and Collaborators

University of Washington

National Heart, Lung, and Blood Institute (NHLBI)

Investigators


Principal Investigator:	Kevin D. O'Brien, MD	University of Washington

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

O'Brien KD, Hippe DS, Chen H, Neradilek MB, Probstfield JL, Peck S, Isquith DA, Canton G, Yuan C, Polissar NL, Zhao XQ, Kerwin WS. Longer duration of statin therapy is associated with decreased carotid plaque vascularity by magnetic resonance imaging. Atherosclerosis. 2016 Feb;245:74-81. doi: 10.1016/j.atherosclerosis.2015.11.032. Epub 2015 Dec 1.

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 plaque progression: a multicenter reproducibility study. Int J Cardiovasc Imaging. 2015 Jan;31(1):95-103. doi: 10.1007/s10554-014-0532-7. Epub 2014 Sep 13.


Responsible Party:	University of Washington
ClinicalTrials.gov Identifier:	NCT00880178 History of Changes
Other Study ID Numbers:	630 R01HL089504
Study First Received:	April 10, 2009
Last Updated:	December 18, 2012
Health Authority:	United States: Federal Government

Keywords provided by University of Washington:


Simvastatin Niacin Vascular Disease Magnetic Resonance Imaging High Density Lipoprotein	Oxidation Proteomics Stroke Cerebrovascular Accident

Additional relevant MeSH terms:


Inflammation Infarction Cardiovascular Diseases Heart Diseases Myocardial Infarction Atherosclerosis Coronary Disease Coronary Artery Disease Pathologic Processes Ischemia Necrosis Myocardial Ischemia Vascular Diseases Arteriosclerosis Arterial Occlusive Diseases	Simvastatin Niacin Niacinamide Nicotinic Acids Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors Vasodilator Agents Vitamin B Complex Vitamins Micronutrients

ClinicalTrials.gov processed this record on September 23, 2016

Plaque Inflammation and Dysfunctional HDL Cholesterol in Participants Receiving Niacin and Statins in the AIM-HIGH Study (The HDL Proteomics Study) (HDL Proteomics)