The Correlation Between the Enzyme Paraoxigenase 1 (PON1) to Carotid Artery Atheromatous Plaque

Carotid Artery Stenosis Clinical Trial

Official title:

The Correlation Between the Enzyme Paraoxigenase 1 (PON1) to Carotid Artery Atheromatous Plaque

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01440036
• Other study ID #: 0032-11-ZIV
• Status: Recruiting
• Phase: N/A
• First received: September 22, 2011
• Last updated: December 15, 2011
• Start date: October 2011
• Est. completion date: October 2014

Study information

• Verified date: December 2011
• Source: Ziv Hospital
• Contact: Tal Salamon, MD
• Phone: 972-50-8434185
• Email: tal.s[@]ziv.health.gov.il
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Observational

Clinical Trial Summary

The objective of the research, is to examine the hypothesis, that the enzyme paraoxygenase 1 ( PON1) can influence carotid artery's atherosclerotic plaque content and stability, and its relation to plasma's enzyme concentration.

Description:

Atherosclerosis is a major risk factor for morbidity and mortality in the western world. It is characterized by the accumulation of fat (cholesterol) in the arterial wall, creation of the atheromatous plagues and the creation of arterial stenosis and occlusion. The cellular content of theses plaques include: fibroblasts, endothelial cells, smooth muscle cells, macrophages, and lipids: phospholipids, cholesterol, oxysterols and fatty acids. Lipids penetration from the blood stream collaborates different proteins, including the anti-atherogenic enzyme - paraoxygenase 1 - PON1. This enzyme has many ani-atherogenic activities, e.g. Protection from oxygenation and increase of cholesterol efflux from macrophages by HDL. Although the enzyme has a verity of substrates and known anti-atherogenous function, its mechanism is still vogue. The enzymes accumulation rate is the function of the advancement of the fatty strike towards advanced lesion. There is evidence that the presence accumulation and activity of the PON1 within the plaque, is a defense mechanism against atherosclerosis development. The assumption to be proved is that PON1 can control plaque's content and influence its atherogenous factors. Furthermore, we will try to identify these factors that the PON1 acts on. Beside plaque's content and PON1's influence on them, we would like to investigate the phenotype of haptoglobin in the subjects that the plaques were removed from. It is known that diabetics that have the genotype haptoglobin 2-2, characterized by increased risk for oxygenation stress and cardiovascular events (up to 5 times). We would like to examine if there is a correlation between plaque's content, PON1's ability to disassemble oxygenized factors within the plaque, and the phenotype to haptoglobin.

Methods: The plaque source will be from carotid endarterectomy, in the vascular unit. This procedure is a routine operation for patients suffering from carotid artery stenosis, based on clinical decisions. The plaques will be transported to a lipid laboratory soon after they will be harvested, will be frozen in liquid nitrogen and processed into powder. This material will be the origin for the proteins we try to extract. Patient's blood samples (that is drawn routinely for the operation) will be the source for the characterization of the haptoglobin's genotype.

It is critical to emphasize that routinely, the plaques are waste products, and only 5 cc of additional blood is withdrawn from the patients for research purposes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: October 2014
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients undergoing CEA

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Carotid Artery Stenosis
• Carotid Stenosis

Intervention

Procedure:
• Carotid endarterectomy
The removal of atherosclerotic plaque from the carotid artery, by surgery

Locations

Country	Name	City	State
Israel	Ziv Medical Center	Safed

Sponsors (1)

Lead Sponsor	Collaborator
Ziv Hospital

Country where clinical trial is conducted

Israel,