Atherothrombosis Markers in Diabetics

NCT ID: NCT02898467

Last Updated: 2016-09-13

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2019-06-30

Brief Summary

Intraplaque hemorrhage is the driving force of atherothrombotic plaque vulnerability to rupture and associated clinical complications. Polymorphonuclear neutrophils (PMNs) represent about 70% of leukocytes and may constitute a source of proteases and oxidants that favour plaque rupture. Our objective is to evaluate PMN activation in atherosclerotic plaque of non-diabetic versus type 2 diabetic patients. For this purpose, investigators will quantify the presence of cell-free DNA, that reflect the formation of neutrophil extracellular traps (NETs) in carotid endarterectomy samples.

Detailed Description

Atherothrombotic plaques of type 2 diabetic patients are characterized by increased neovascularization and associated intraplaque hemorrhage relative to non-diabetic patients that could account for a major incidence of clinical complications. In parallel, Type 2 diabetic patients are characterized by an increased intracellular oxidative stress in circulating PMNs leading to a primed phenotype. PMN priming could be triggered via their receptor for advanced glycation endproducts. In particular, glycated albumin may activate NADPH oxidase and thus promote the production of reactive oxygen species. Under strong activation, PMNs have been described to release NETs that are constituted by externalized nucleosomes associating DNA, histones and enzymes initially present in granules (such as myeloperoxidase, matrix metalloproteinase 9 or elastase). Our hypothesis is that in diabetic conditions, PMNs could be activated within atherothrombotic plaques and thus represent a trigger for plaque rupture. In the present study, we will evaluate PMN activation in carotid plaques of diabetic vs non-diabetic patients as well as in plasma samples of the same patients. For this purpose, all patients that will undergo carotid surgery by endarterectomy will be enrolled in our study and blood samples will be collected the day before the surgery for preparation of plasma and serum. The endarterectomy sample will be collected, dissected into culprit area of the plaque (CP) and the adjacent non-complicated plaque (NCP), incubated separately in culture medium for 24h at 37°C. The resulting conditioned medium will be aliquoted and stored at -80°C for the different assessments. A representative section of the CP will be saved at the moment of dissection for histological evaluation (presence of neovessels/intraplaque hemorrhage, calcifications, lipids, etc). Markers of neutrophil activation, of intraplaque hemorrhage, of glycation and of oxidative stress will be quantified in both conditioned medium and plasma.

Conditions

Diabetes; Atherothrombosis; Cardiovascular Disease

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

diabetics

Type 2 diabetic patients exhibiting fasting glycemia value over 7 mmol/L or glycated hemoglobin value over 6.5% or type 2 diabetic patients under oral anti-diabetic treatment or type 2 diabetic patient under insulin treatment and in which diabetes has been diagnosed after the age of 45 y

diabetics

Intervention Type: OTHER

additional blood and urine collection during usual medical care endarterectomy samples during usual medical care

non-diabetics

patients without diagnosed diabetes exhibiting fasting glycemia value under 7 mmol/L

non-diabetics

Intervention Type: OTHER

additional blood and urine collection during usual medical care endarterectomy samples during usual medical care

Interventions

diabetics

additional blood and urine collection during usual medical care endarterectomy samples during usual medical care

Intervention Type: OTHER

non-diabetics

additional blood and urine collection during usual medical care endarterectomy samples during usual medical care

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Adult patients with planned endarterectomy
• Affiliated to social security rights
• Signed inform consent

Exclusion Criteria

• pregnancy
• Autoimmune disease, chronic inflammatory disease, neoplasia
• Type 1 diabetes

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Academic Health Science Centres

OTHER

Sponsor Role: collaborator

Centre Hospitalier Universitaire de la Réunion

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

XAVIER DEBUSSCHE, MD

Role: PRINCIPAL_INVESTIGATOR

CHU DE LA REUNION

Locations

Department of endocrinology, University Hospital Reunion Island - Felix Guyon Site

Saint Denis de La Réunion, , France

Countries

France

Central Contacts

CHRISTINE JUHEL, PHD

Role: CONTACT

christine.juhel@chu-reunion.fr

+262262359949

Other Identifiers

2013/CHU/06

Identifier Type: -

Identifier Source: org_study_id