Coronary Atherosclerosis, Coronary Small Vessel Disease, Endothelial Dysfunction
Conditions
Brief summary
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
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.
Interventions
DEVICEOptical Coherence Tomography (C7 XR Dragonfly )
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.
Sponsors
GlaxoSmithKline
Mayo Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantification of plaque vulnerability. | change from baseline to six months | 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. |
Countries
United States
Outcome results
None listed