Plaque Inflammation and Dysfunctional HDL in AIM-HIGH

Cardiovascular Diseases Clinical Trial

— HDL Proteomics  

Official title:

Plaque Inflammation and Dysfunctional HDL in AIM-HIGH

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00880178
• Other study ID #: 28201
• Secondary ID: R01HL089504
• Status: Completed
• Start date: May 2008
• Est. completion date: September 2011

Study information

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

Clinical Trial Summary

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.

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 simvastatin, which is a type of statin medication, or simvastatin 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 324
• Est. completion date: September 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

Inclusion Criteria:

• Eligible for main AIM-HIGH study (NCT00120289)

• Willing to provide informed consent for participation in this substudy

Related Conditions & MeSH terms

• Atherosclerosis
• Cardiovascular Diseases
• Coronary Artery Disease
• Coronary Disease
• Heart Diseases
• Infarction
• Inflammation
• Myocardial Infarction

Intervention

Drug:
• Simvastatin and 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
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	St. Michael's Health Centre	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
United States	University of Maryland	Baltimore	Maryland
United States	Cardiovascular Associates	Birmingham	Alabama
United States	St. Vincent Charity Hospital	Cleveland	Ohio
United States	Duke University	Durham	North Carolina
United States	Wake Forest University, Geriatrics	Greensboro	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	HealthPartners Riverside Clinic	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	Christiana Care Health Services	Newark	Delaware
United States	Cardiology Consultants of Philadelphia	Philadelphia	Pennsylvania
United States	Pennsylvania Cardiology Associates	Philadelphia	Pennsylvania
United States	Philadelphia VA Medical Center	Philadelphia	Pennsylvania
United States	Cardiovascular Consultants	Phoenix	Arizona
United States	Portland VA Medical Center	Portland	Oregon
United States	McGuire VA Medical Center	Richmond	Virginia
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, Cardiology	Winston-Salem	North Carolina
United States	Wake Forest University, Endocrinology	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 (6)

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 KD, 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 D — View Citation

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. Ath — View Citation

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. Summary of clinical and laboratory data of study subjects with and without DCE-MRI plaque measurements in the AIM-HIGH clini — View Citation

Sun J, Zhao XQ, Balu N, Neradilek MB, Isquith DA, Yamada K, Cantón G, Crouse JR 3rd, Anderson TJ, Huston J 3rd, O'Brien K, Hippe DS, Polissar NL, Yuan C, Hatsukami TS. Carotid Plaque Lipid Content and Fibrous Cap Status Predict Systemic CV Outcomes: The M — 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	Change in HDL oxidation and proteomics		Measured at Year 2
Secondary	Comparison of HDL oxidation and proteomics changes between participants receiving statins versus participants receiving statins plus niacin		Measured at Year 2
Secondary	Comparison of change in an MRI marker of plaque inflammation between participants receiving statins versus participants receiving statins plus niacin		Measured at Year 2
Secondary	Comparison of changes in HDL oxidation and proteomics with change in an MRI marker of plaque inflammation		Measured at Year 2
Secondary	Change in an MRI marker of plaque inflammation		Measured at Year 2