Clinical trial NCT01837823: YELLOW II Study: Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering
Official title: YELLOW II Study: Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obstructive Coronary Artery Disease
Coronary Artery Disease
Keywords: Coronary artery disease
Lipid
Regression
Plaque
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Texas Heart Institute (Wafic Said Molecular Cardiology Research Lab)
name: AstraZeneca
name: InfraReDx (indirect)
First posted: 2013-04-23
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Coronary artery disease (CAD) remains a leading cause of death in most countries. It is well known that the reduction of cholesterol levels by statin therapy is associated with significant decreases in plaque burden. REVERSAL, ASTEROID, and more recently the SATURN II trial showed that in patients with CAD, lipid lowering with atorvastatin or rosuvastatin respectively reduced progression of coronary atherosclerosis, even causing plaque regression of some lesions. CAD clinical events are related to plaque instability due to lipid content and activity within the atherosclerotic plaque. The investigators recently completed the YELLOW I study, and identified that intensive statin therapy (rosuvastatin 40mg) was associated with a reduction in the amount of lipid in obstructive coronary plaques, as measured by near-infrared spectroscopy (NIRS). The YELLOW II study is designed to expand and build upon these results, and to provide mechanistic insights into the potential benefits of intensive statin therapy on atherosclerotic plaques.

Detailed description: YELLOW II is a single site study and will assess the regression of plaque lipid content and changes in plaque morphology from atherosclerotic lesions after high-dose statin therapy by utilizing NIRS, IVUS and optical coherency tomography (OCT) imaging modalities in the coronary arteries. We propose to image non-culprit coronary lesions using these modalities in patients with two or three diseased coronary vessels deemed to warrant intervention on clinical grounds. Thus, at the time of enrolment patients will undergo Percutaneous Coronary Intervention (PCI) of a non-study culprit lesion, and triple-modality imaging of the potential non-culprit ('YELLOW') lesion. If there is high baseline lipid content in the non-culprit YELLOW lesion (max 4mm LCBI \> 150), patients will be formally entered into this study. Following this, all enrolled subjects will receive high-dose lipid lowering therapy (rosuvastatin 40mg daily). The non-culprit YELLOW lesion will undergo staged intervention 8-12 weeks following study enrolment and baseline imaging. At this time the YELLOW lesion will be reimaged to determine whether high-dose statin therapy caused a reduction in lipid content as assessed by NIRS, and other altered plaque morphology as assessed by OCT and IVUS. In addition, both at baseline and at the time of final non-culprit YELLOW lesion PCI, blood samples will be drawn during baseline and follow-up procedure to characterize reverse cholesterol transport by ability of patient HDL to accept cholesterol from cholesterol-laden (mouse J774) macrophage (cholesterol efflux) and the effect of patient HDL and apolipoprotein A1 on macrophage gene expression and migration.

Eligibility criteria: Inclusion Criteria:

* Patients \>18 years of age and willing to participate.
* Fluency in either English or Spanish.
* Stable patients who will undergo cardiac catheterization and PCI (intent to stent).
* Patient is willing to go on high-dose cholesterol lowering medication for the duration of the study
* Signed written Informed Consent.
* Women of childbearing potential must agree to be on an acceptable method of birth control/contraceptive such as barrier method (condoms/diaphragm); hormonal contraceptives (birth control pills, implants (Norplant) or injections (Depo-Provera)); Intrauterine Device.
* Proposed non-culprit YELLOW study lesion with max 4mm LCBI ≥ 150.

Exclusion Criteria:

* Patients who have acute myocardial infarction (ST-segment elevation presentation, new Q waves or non-ST segment elevation with CK-MB \> 5 times above the upper normal (31.5 ng/ml) within 72 hours).
* Patients who are in cardiogenic shock.
* Patients requiring coronary artery bypass graft surgery.
* Patients with platelet count \< 100,000 cell/mm3.
* Patients who have co-morbidity which reduces life expectancy to one year.
* Patients who are currently participating in another investigational drug/device study.
* Patients with liver disease.
* Patient with creatinine \> 2.0 mg/dL.
* Pregnant women and women of childbearing potential who intend to have children during the duration of the trial.
* Patients having undergone heart transplantation, or those that may undergo heart transplantation during the study period.
* Active autoimmune disease.
* Nursing mothers

Primary outcomes:
measure: Correlation Between Plaque Morphology and HDL Functionality
timeFrame: baseline and 8-12 weeks
measure: Correlation Between the Change in Fibrous Cap Thickness and Hs-CRP
timeFrame: baseline and 8-12 weeks
Secondary outcomes:
measure: Maximal 4mm Lipid Core Burden Index (LCBI 4mm Max)
timeFrame: baseline and at 8-12 weeks
measure: Fibrous Cap Thickness (FCT) by OCT
timeFrame: baseline and at 8-12 weeks
measure: IVUS Imaging Measures
timeFrame: Baseline and 8 weeks
measure: Inflammatory and Lipid Parameters
timeFrame: baseline and at 8-12 weeks
measure: Lesion LCBI
timeFrame: at baseline and at 8-12 weeks
measure: LCBI 4mm at Same Anatomical Site
timeFrame: at baseline and at 8-12 weeks
measure: Change in Atheroma Volume
timeFrame: baseline and at 8-12 weeks
measure: Biomarker Release
timeFrame: within 24 hrs of PCI
measure: Correlation of Baseline Lipid Parameters With Baseline LCBI4mm Max
timeFrame: baseline
measure: Plaque Morphology as Related to Haptoglobin
timeFrame: baseline and at 8-12 weeks
measure: Mechanism of Reverse Cholesterol Transport
timeFrame: baseline and at 8-12 weeks
measure: Correlation of Changes in Plaque Morphology
timeFrame: baseline and at 8-12 weeks
measure: MACE
timeFrame: at 30 days
measure: MACE
timeFrame: at 1 year
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Annapoorna Kini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Jason Kovacic, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kini AS, Vengrenyuk Y, Shameer K, Maehara A, Purushothaman M, Yoshimura T, Matsumura M, Aquino M, Haider N, Johnson KW, Readhead B, Kidd BA, Feig JE, Krishnan P, Sweeny J, Milind M, Moreno P, Mehran R, Kovacic JC, Baber U, Dudley JT, Narula J, Sharma S. Intracoronary Imaging, Cholesterol Efflux, and Transcriptomes After Intensive Statin Treatment: The YELLOW II Study. J Am Coll Cardiol. 2017 Feb 14;69(6):628-640. doi: 10.1016/j.jacc.2016.10.029. Epub 2016 Oct 29.