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Lp-PLA2 and Coronary Atherosclerosis in Humans (AIM 1 and II)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Mayo Clinic
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Amir Lerman, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01557088
First received: March 15, 2012
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

The majority of the acute coronary events are caused by coronary artery segments with minimal luminal disease, but with potentially significant vascular wall inflammation and oxidative stress leading to plaque vulnerability. It has become apparent that an initial injury at the endothelial surface, is the primary site of the mechanisms involved and a role for vascular inflammation and the interaction with oxidative stress continues to emerge. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel biomarker for vascular wall inflammation that circulates in the blood bound to both low density (LDL) and high density (HDL) lipoprotein and promotes vascular inflammation. Circulating levels of Lp-PLA2 mass and activity are an independent risk factor for cardiovascular events. Recent studies, demonstrating that Lp-PLA2 is also associated with coronary endothelial dysfunction. However, the relationship between Lp-PLA2 and early atherosclerotic changes in the coronary arteries, and the contribution of lipoprotein binding to the deleterious potential of Lp- PLA2 have not been elucidated. Our working hypothesis is that the endogenous local activation of the Lp-PLA2 pathway plays an integral role in early coronary atherosclerosis and contributes to the mechanism of coronary endothelial dysfunction and the structural and mechanical properties reflecting plaque vulnerability. Thus, the current application will characterize prospectively the correlation between the functional, mechanical, and structural vascular wall properties, and the systemic as well as the coronary activity of the Lp-PLA2 pathway.


Condition Intervention
Coronary Atherosclerosis
Endothelial Dysfunction
Other: Blood sampling from the Coronary Sinus and Aorta
Procedure: Intravascular Ultrasound of the coronary artery.

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Lp-PLA2, Progenitor Cells and Coronary Atherosclerosis in Humans

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Lp-PLA2 Assessment [ Time Frame: baseline endothelial function assessment 6 months ] [ Designated as safety issue: No ]
    AIM 1: To assess the relationship between the 3 inflammatory measures of the Lp-PLA2 pathway (Lp-PLA2 mass, Lp-PLA2 activity and LysoPC) with endothelial function (as measured by the percent change in CAD (coronary artery disease) [Ach] and by the length of segments with endothelial dysfunction and plaque vulnerability (as measured by the necrotic core percent volume). AIM II: To assess the association between the percent of Lp-PLA2 residing on LDL and endothelial function (again measured by percent change in CAD [Ach], percent change in CBF (coronary blood flow)[Ach], and the length of endothelial dysfunction).


Estimated Enrollment: 200
Study Start Date: February 2009
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Other: Blood sampling from the Coronary Sinus and Aorta
    Blood samples will be obtained from the aorta and the coronary sinus during the clinically scheduled angiogram and endothelial function testing.
    Procedure: Intravascular Ultrasound of the coronary artery.
    Intravascular Ultrasound will be completed for those subjects testing positive for coronary endothelial dysfunction during a clinically scheduled angiogram and endothelial function testing.
Detailed Description:

Aim I: Hypothesis: The extent of endothelial dysfunction will correlate with production of Lp-PLA2 and oxidative stress and correlates with the tissue characteristics of plaque vulnerability. The investigators will define the systemic and coronary gradient and production of markers of inflammation and oxidative stress and the presence of coronary endothelial dysfunction in patients with early coronary atherosclerosis.

Aim II: Hypothesis: The distribution of Lp-PLA2 on the LDL is associated with greater coronary endothelial dysfunction and correlates with the degree coronary atherosclerosis and plaque vulnerability. The investigators will define the distribution of Lp-PLA2 in patients with early coronary atherosclerosis and endothelial dysfunction.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients undergoing coronary angiography including endothelial function testing
  • male and female
  • age 18 up to age 85

Exclusion Criteria:

  • Heart failure with ejection fraction less that 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 into the study
  • significant endocrine, hepatic or renal disorders
  • local or systemic infectious disease within 4 weeks prior to entry into study
  • pregnancy or lactation (women of child-bearing age will have a pregnancy test prior to angiogram)
  • mental instability
  • federal medical center inmates
  • hemoglobin less than 12 mg/dL
  • severe asthma
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01557088

Contacts
Contact: Cindy M Woltman, RN 507-266-4095 woltman.cindy@mayo.edu

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Principal Investigator: Amir Lerman, MD         
Sub-Investigator: Abhiram Prasad, MD         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Amir Lerman, MD Mayo Clinic
  More Information

No publications provided

Responsible Party: Amir Lerman, Professor of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01557088     History of Changes
Other Study ID Numbers: 08-008161, 5R01HL92954-01A1-05, 1R01 AG31750-01A2-04
Study First Received: March 15, 2012
Last Updated: August 20, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by Mayo Clinic:
coronary artery disease
coronary artery spasm
small vessel coronary artery disease

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Coronary Artery Disease
Myocardial Ischemia
Arterial Occlusive Diseases
Cardiovascular Diseases
Coronary Disease
Heart Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 24, 2014