Obstructive Coronary Artery DiseasePhase 2NCT01837823
YELLOW II Study: Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering
A Phase 2 study testing rosuvastatin in people with Obstructive Coronary Artery Disease and Coronary Artery Disease, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Obstructive Coronary Artery Disease, Coronary Artery Disease
- What is being tested?
- rosuvastatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 91 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Apr 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
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.
Read the 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.
- Being tested
- rosuvastatin
- Keywords
- Coronary artery disease, Lipid, Regression, Plaque
- Medical subject headings
- Coronary Artery Disease, Plaque, Amyloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rosuvastatinDrug
Also called Crestor
All subjects will receive rosuvastatin 40mg/day for 8-12 weeks
| Study group | Role | What they receive |
|---|---|---|
| rosuvastatin | Experimental | All subjects will receive rosuvastatin 40mg/day Receives: Drug: rosuvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation Between Plaque Morphology and HDL Functionality
Correlation between the changes in plaque morphology composition by intravascular imaging with changes in HDL functionality. HDL functionality is measured by the Cholesterol Efflux Capacity (CEC). Plaque morphology is represented by the Fibrous Cap Thickness.
Measured: baseline and 8-12 weeks
Correlation Between the Change in Fibrous Cap Thickness and Hs-CRP
Correlation between the change in plaque morphology composition by intravascular imaging with inflammatory cell activity.
Measured: baseline and 8-12 weeks
Secondary outcomes (14)
Maximal 4mm Lipid Core Burden Index (LCBI 4mm Max)
Maximum LCBI 4mm (ΔLCBI4mm max) of the non-culprit YELLOW lesion at baseline and 8-12 weeks thereafter.
LCBI4mm max : 4-mm long segment with maximum lipid core burden index (LCBI), where the LCBI is calculated as the fraction of yellow pixels on a chemogram x 1000. Each pixel on the chemogram represents a probability of lipid presence in the given region; pixels are color-coded on a red-to-yellow color scale, with the low probability of lipid shown as red and the high probability of lipid shown as yellow.
Measured: baseline and at 8-12 weeks
Fibrous Cap Thickness (FCT) by OCT
ΔFibrous Cap Thickness measured by OCT at baseline and at 8-12 weeks
Measured: baseline and at 8-12 weeks
IVUS Imaging Measures
Correlation between ΔLCBI4mm max will be related to Δ values from baseline to 8-12 weeks thereafter in specific IVUS (ΔPlaque burden) imaging measures. Plaque burden is Plaque + Media divided by Total Plaque Area in %.
Measured: Baseline and 8 weeks
Inflammatory and Lipid Parameters
ΔLCBI4mm max will be related to Δ values from baseline to 8-12 weeks thereafter in inflammatory and lipid parameters responses to patient-derived samples.
Measured: baseline and at 8-12 weeks
Lesion LCBI
As related to other outcomes, change in LCBI measured across the entire lesion (rather than ΔLCBI4mm max). The LCBI Score, computed as the fraction of valid pixels within the scanned region that exceeded a LCP probability of 0.6 multiplied by 1000, summarized the amount of LCP in the entire scanned region of the coronary vessel on a 0-to-1000 scale .
Measured: at baseline and at 8-12 weeks
LCBI 4mm at Same Anatomical Site
As related to other outcomes, change in LCBI 4mm measured at the identical anatomical site at both time points, as defined by the LCBI4mm max site at baseline (rather than ΔLCBI4mm max).
LCBI4mm: 4-mm long segment with maximum lipid core burden index (LCBI), where the LCBI is calculated as the fraction of yellow pixels on a chemogram x 1000. Each pixel on the chemogram represents a probability of lipid presence in the given region; pixels are color-coded on a red-to-yellow color scale, with the low probability of lipid shown as red and the high probability of lipid shown as yellow.
Measured: at baseline and at 8-12 weeks
Change in Atheroma Volume
Change in total atheroma volume (TAV) and lumen cross sectional area on OCT.
Measured: baseline and at 8-12 weeks
Biomarker Release
Post procedure CK-MB, Troponin-I release at final YELLOW lesion PCI.
Measured: within 24 hrs of PCI
Correlation of Baseline Lipid Parameters With Baseline LCBI4mm Max
Correlation of baseline lipid parameters with baseline LCBI4mm max
Measured: baseline
Plaque Morphology as Related to Haptoglobin
To relate changes in plaque lipid content and morphology to the patient haptoglobin genotype.
Measured: baseline and at 8-12 weeks
Mechanism of Reverse Cholesterol Transport
To assess the mechanism of reverse cholesterol transport that arises with high-dose statin therapy, as related to changes in plaque lipid content and morphology, and systemic vascular inflammation. Reverse cholesterol transport (RCT) is a pathway by which accumulated cholesterol is transported from the vessel wall to the liver for excretion, thus preventing atherosclerosis.
Measured: baseline and at 8-12 weeks
Correlation of Changes in Plaque Morphology
Correlation of changes in plaque morphology by OCT, IVUS and NIRS with the perturbations in peripheral blood mononuclear cell transcriptome using microarray analysis.
data not collected for this measure.
Measured: baseline and at 8-12 weeks
MACE
Major Adverse Cardiac Events (MACE) defined as a combined clinical endpoint of death, MI (Q wave or non Q-wave with CK-MB >3 times above the upper normal limit (48 U/L), urgent revascularization or stroke at 30 days.
Measured: at 30 days
MACE
Major Adverse Cardiac Events (MACE) defined as a combined clinical endpoint of death, MI (Q wave or non Q-wave with CK-MB >3 times above the upper normal limit (48 U/L), urgent revascularization or stroke at 1 year.
Measured: at 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2013 (estimated)
- Study startJul 2013
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Obstructive Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- Texas Heart Institute (Wafic Said Molecular Cardiology Research Lab), AstraZeneca, InfraReDx (indirect)
- Responsible party
- Principal investigator, Annapoorna Kini, Icahn School of Medicine at Mount Sinai
- Investigators
- Annapoorna Kini, MD, Principal investigator, Icahn School of Medicine at Mount SinaiJason Kovacic, MD, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01837823
- Sponsor's protocol ID
- GCO 12-1507
- Other IDs
- HS#: 12-00741
- Status last verified
- Jan 2018
- First submitted
- 5 Apr 2013
- Last updated
- 13 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 27989886
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- YELLOW II Study: Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering
- ClinicalTrials.gov ID
- NCT01837823
- Acronym / sponsor ID
- GCO 12-1507
- Keywords
- Coronary artery disease, Lipid, Regression, Plaque
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- Texas Heart Institute (Wafic Said Molecular Cardiology Research Lab), AstraZeneca, InfraReDx (indirect)
- Study start
- Jul 2013
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 23 Apr 2013 (estimated)
- Results
- Posted 13 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| rosuvastatin | Experimental | Drug: rosuvastatinAll subjects will receive rosuvastatin 40mg/day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rosuvastatinAlso: CrestorAll subjects will receive rosuvastatin 40mg/day for 8-12 weeks | Drug | rosuvastatin |
Primary outcome
Correlation Between Plaque Morphology and HDL Functionality
Time frame: baseline and 8-12 weeks
Correlation between the changes in plaque morphology composition by intravascular imaging with changes in HDL functionality. HDL functionality is measured by the Cholesterol Efflux Capacity (CEC). Plaque morphology is represented by the Fibrous Cap Thickness.
Correlation Between the Change in Fibrous Cap Thickness and Hs-CRP
Time frame: baseline and 8-12 weeks
Correlation between the change in plaque morphology composition by intravascular imaging with inflammatory cell activity.
14 secondary outcomes
Maximal 4mm Lipid Core Burden Index (LCBI 4mm Max)
Time frame: baseline and at 8-12 weeks
Fibrous Cap Thickness (FCT) by OCT
Time frame: baseline and at 8-12 weeks
IVUS Imaging Measures
Time frame: Baseline and 8 weeks
Inflammatory and Lipid Parameters
Time frame: baseline and at 8-12 weeks
Lesion LCBI
Time frame: at baseline and at 8-12 weeks
LCBI 4mm at Same Anatomical Site
Time frame: at baseline and at 8-12 weeks
Change in Atheroma Volume
Time frame: baseline and at 8-12 weeks
Biomarker Release
Time frame: within 24 hrs of PCI
Correlation of Baseline Lipid Parameters With Baseline LCBI4mm Max
Time frame: baseline
Plaque Morphology as Related to Haptoglobin
Time frame: baseline and at 8-12 weeks
Mechanism of Reverse Cholesterol Transport
Time frame: baseline and at 8-12 weeks
Correlation of Changes in Plaque Morphology
Time frame: baseline and at 8-12 weeks
MACE
Time frame: at 30 days
MACE
Time frame: at 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27989886Kini 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annapoorna Kini, MD principal investigator
Icahn School of Medicine at Mount Sinai
Jason Kovacic, MD, PhD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rosuvastatin in people with Obstructive Coronary Artery Disease and Coronary Artery Disease, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation Between Plaque Morphology and HDL Functionality (time frame: baseline and 8-12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01837823, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2018.