Assessment of Coronary Plaque Composition Using Optical Coherence Tomography

Study Overview
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Brief Summary
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The investigator's hypothesis is that local activation of the endogenous Lp-PLA2 plays an integral role in early atherosclerosis, and contributes to the mechanism of coronary endothelial dysfunction and to the structural and mechanical properties that characterize plaque vulnerability. Thus, the investigators study will characterize prospectively the correlation between the functional and structural vascular wall properties, and the activity of the Lp-PLA2 pathway.

Detailed Description
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The present study was a substudy of our National Institute of Health (NIH) funded and Institutional Review Board (IRB) approved (08-008161) protocol Lp-PLA2 and Coronary Atherosclerosis in Humans and (10-000044) Lp-PLA2 and Coronary Atherosclerosis in Humans Aim III in which the investigators are examining the impact of long-term inhibition of Lp-PLA2, with a specific novel inhibitor, on Lp-PLA2 activity and improvement in coronary endothelial function. This substudy will use Optical Coherence Tomography (OCT) to quantify alternate features of plaque vulnerability including superficial microcalcification, fibrous cap thickness, and plaque macrophage content at baseline and again at 6 months following Lp-PLA2 inhibition. The study will provide insight into the role of the endogenous Lp-PLA2 in early coronary atherosclerosis, a potential therapeutic target for early coronary atherosclerosis in humans.

Official Title
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Assessment of Coronary Plaque Composition Using Optical Coherence Tomography During Chronic Inhibition of Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Activity

Conditions
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Coronary Atherosclerosis, Endothelial Dysfunction, Coronary Small Vessel Disease

Intervention / Treatment
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* Device: Optical Coherence Tomography (C7 XR Dragonfly )


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 18 years and < 85 years referred to our cardiac catheterization laboratory for coronary vasomotion testing are found to have coronary endothelial dysfunction. Exclusion Criteria: these include heart failure ejection fraction < 40% unstable angina myocardial infarction or angioplasty within 6 months prior to entry into the study use of investigational agents within 1 month of entry into the study, patients who require treatment with positive inotropic agents other than digoxin during the study patients with cerebrovascular accident within 6 months prior to entry the study significant endocrine, hepatic or renal, disorders local or systemic infectious disease within 4 weeks prior to entry into study pregnancy or lactation mental instability Federal Medical Center inmates

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: OCT at baseline<br>Subjects enrolled in the NIH funded and IRB approved (08-008161) protocol Lp-PLA2 and Coronary Atherosclerosis in Humans with a positive diagnosis of coronary artery endothelial dysfunction will be studied using Optical Coherence Tomography during the angiogram at baseline. | Device: Optical Coherence Tomography (C7 XR Dragonfly )<br>* Evaluation of the coronary artery using Optical Coherence Tomography utilizing the Dragonfly OCT catheter following a clinically indicated angiogram and endothelial function testing with a positive diagnosis of endothelial dysfunction. The procedure is repeated following 6 months of Lp-PLa2 inhibition or placebo.<br>* Other names: C7 XR Dragonfly Optical Coherence Tomography system;|
| Other: OCT following 6 month Lp-PLa2 inhibition<br>Subjects who are enrolled in IRB 10-000044 Lp-PLA2 and Coronary Atherosclerosis in Humans Aim III a study in which the investigators are examining the impact of long-term inhibition of Lp-PLA2, with a specific novel inhibitor or placebo, on Lp-PLA2 activity and improvement in coronary endothelial function will be studied using Optical Coherence Tomography during the 6 month return angiogram. | Device: Optical Coherence Tomography (C7 XR Dragonfly )<br>* Evaluation of the coronary artery using Optical Coherence Tomography utilizing the Dragonfly OCT catheter following a clinically indicated angiogram and endothelial function testing with a positive diagnosis of endothelial dysfunction. The procedure is repeated following 6 months of Lp-PLa2 inhibition or placebo.<br>* Other names: C7 XR Dragonfly Optical Coherence Tomography system;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of plaque vulnerability. | Following recruitment of the total study population and 6-months therapy with the Lp-PLA2 inhibitor or placebo, using Optical Coherence Tomography (OCT) we will quantify alternate features of plaque vulnerability including superficial microcalcification, fibrous cap thickness, and plaque macrophage content comparing baseline and 6 months studies. | change from baseline to six months |