Clinical trial NCT02898467: Atherothrombosis Markers in Diabetics
Official title: Comparison of Atherothrombosis Markers From Aortic Atheroma in Diabetic and Non-diabetic Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Diabetes
Atherothrombosis
Cardiovascular Disease
Lead sponsor: Centre Hospitalier Universitaire de la Réunion
Sponsor class: OTHER
Collaborators: name: Academic Health Science Centres
First posted: 2016-09-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Diabetics and non-diabetics with planned endartectomy

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.

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

Primary outcomes:
measure: Neutrophile activation assessed by free DNA levels in atherothrombotic plaques
timeFrame: On day 1 (day of the surgery)
Secondary outcomes:
measure: Neutrophile activation assessed by other makers than free DNA levels in atherothrombotic plaques
timeFrame: On day 1 (day of the surgery)
measure: Intraplaque hemorrhage and oxidative stress assessed in plasma and aortic tissue
timeFrame: From day 0 (day before the surgery) to day 1 (day of the surgery)
measure: Correlation between plasma and atherothrombotic plaque markers assessement
timeFrame: From day 0 (day before the surgery) to day 1 (day of the surgery)
measure: Atherothrombosis characterization assessed by histological analysis
timeFrame: On day 1 (day of the surgery)
Other outcomes:
measure: Banking of biological samples
timeFrame: From day 0 (day before the surgery) to day 1 (day of the surgery)
Locations:
city: Saint Denis de La Réunion
country: France
facility: Department of endocrinology, University Hospital Reunion Island - Felix Guyon Site
Study officials:
affiliation: CHU DE LA REUNION
name: XAVIER DEBUSSCHE, MD
role: PRINCIPAL_INVESTIGATOR
References: