Atherothrombosis Markers in Diabetics

Diabetes Clinical Trial

— MADI  

Official title:

Comparison of Atherothrombosis Markers From Aortic Atheroma in Diabetic and Non-diabetic Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02898467
• Other study ID #: 2013/CHU/06
• Status: Not yet recruiting
• Phase: N/A
• First received: September 8, 2016
• Last updated: September 12, 2016
• Start date: October 2016
• Est. completion date: June 2019

Study information

• Verified date: September 2016
• Source: Centre Hospitalier Universitaire de la Réunion
• Contact: CHRISTINE JUHEL, PHD
• Phone: +262262359949
• Email: christine.juhel[@]chu-reunion.fr
• Is FDA regulated: No
• Health authority: France: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santéFrance: The Commission nationale de l’informatique et des libertés
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: June 2019
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Atherothrombosis
• Cardiovascular Disease
• Cardiovascular Diseases
• Diabetes

Intervention

Other:
• diabetics
additional blood and urine collection during usual medical care endarterectomy samples during usual medical care
• non-diabetics
additional blood and urine collection during usual medical care endarterectomy samples during usual medical care

Locations

Country	Name	City	State
France	Department of endocrinology, University Hospital Reunion Island - Felix Guyon Site	Saint Denis de La Réunion

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de la Réunion	Academic Health Science Centres

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Banking of biological samples	Constitution of a biobank available for different assays of markers and for the discovery of new biomarkers of plaques in type 2 diabetic patients (open approaches, such as differential proteomics)	From day 0 (day before the surgery) to day 1 (day of the surgery)	No
Primary	Neutrophile activation assessed by free DNA levels in atherothrombotic plaques	Ability of cfDNA concentration in the conditioned medium to discriminate atherothrombotic plaques from diabetic vs non-diabetic patients	On day 1 (day of the surgery)	No
Secondary	Neutrophile activation assessed by other makers than free DNA levels in atherothrombotic plaques	Evaluation of PMN activation by assays other than cfDNA (myeloperoxidase, elastase/antielastase complexes, MMP9/neutrophil-gelatinase associated lipocalin NGAL) in the conditioned media and in plasma	On day 1 (day of the surgery)	No
Secondary	Intraplaque hemorrhage and oxidative stress assessed in plasma and aortic tissue	Evaluation of markers reflecting the presence of intraplaque hemorrhage and of oxidative stress in conditioned medium and in plasma (CD163, heme, carbonylated proteins, glycated albumin...)	From day 0 (day before the surgery) to day 1 (day of the surgery)	No
Secondary	Correlation between plasma and atherothrombotic plaque markers assessement	Correlations between markers released by the plaque and plasma markers (evaluation of the impact of atherothrombosis at a circulating level)	From day 0 (day before the surgery) to day 1 (day of the surgery)	No
Secondary	Atherothrombosis characterization assessed by histological analysis	Histological characterization of plaques assessed by quantification of neovessels, calcification, lipids composition	On day 1 (day of the surgery)	No