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Atherothrombosis Markers in Diabetics (MADI)

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ClinicalTrials.gov Identifier: NCT02898467
Recruitment Status : Unknown
Verified September 2016 by Centre Hospitalier Universitaire de la Réunion.
Recruitment status was:  Not yet recruiting
First Posted : September 13, 2016
Last Update Posted : September 13, 2016
Sponsor:
Collaborator:
Academic Health Science Centres
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de la Réunion

Tracking Information
First Submitted Date September 8, 2016
First Posted Date September 13, 2016
Last Update Posted Date September 13, 2016
Study Start Date October 2016
Estimated Primary Completion Date November 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: September 12, 2016)
Neutrophile activation assessed by free DNA levels in atherothrombotic plaques [ Time Frame: On day 1 (day of the surgery) ]
Ability of cfDNA concentration in the conditioned medium to discriminate atherothrombotic plaques from diabetic vs non-diabetic patients
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: September 12, 2016)
  • Neutrophile activation assessed by other makers than free DNA levels in atherothrombotic plaques [ Time Frame: On day 1 (day of the surgery) ]
    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
  • Intraplaque hemorrhage and oxidative stress assessed in plasma and aortic tissue [ Time Frame: From day 0 (day before the surgery) to day 1 (day of the surgery) ]
    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...)
  • Correlation between plasma and atherothrombotic plaque markers assessement [ Time Frame: From day 0 (day before the surgery) to day 1 (day of the surgery) ]
    Correlations between markers released by the plaque and plasma markers (evaluation of the impact of atherothrombosis at a circulating level)
  • Atherothrombosis characterization assessed by histological analysis [ Time Frame: On day 1 (day of the surgery) ]
    Histological characterization of plaques assessed by quantification of neovessels, calcification, lipids composition
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 12, 2016)
Banking of biological samples [ Time Frame: From day 0 (day before the surgery) to day 1 (day of the surgery) ]
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)
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Atherothrombosis Markers in Diabetics
Official Title Comparison of Atherothrombosis Markers From Aortic Atheroma in Diabetic and Non-diabetic Patients
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.
Study Type Observational
Study Design Observational Model: Case Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
plasma and serum samples carotid endarterectomy samples urinary samples
Sampling Method Non-Probability Sample
Study Population Diabetics and non-diabetics with planned endartectomy
Condition
  • Diabetes
  • Atherothrombosis
  • Cardiovascular Disease
Intervention
  • Other: diabetics
    additional blood and urine collection during usual medical care endarterectomy samples during usual medical care
  • Other: non-diabetics
    additional blood and urine collection during usual medical care endarterectomy samples during usual medical care
Study Groups/Cohorts
  • 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
    Intervention: Other: diabetics
  • non-diabetics
    patients without diagnosed diabetes exhibiting fasting glycemia value under 7 mmol/L
    Intervention: Other: non-diabetics
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: September 12, 2016)
100
Original Estimated Enrollment Same as current
Estimated Study Completion Date June 2019
Estimated Primary Completion Date November 2018   (Final data collection date for primary outcome measure)
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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT02898467
Other Study ID Numbers 2013/CHU/06
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Centre Hospitalier Universitaire de la Réunion
Study Sponsor Centre Hospitalier Universitaire de la Réunion
Collaborators Academic Health Science Centres
Investigators
Principal Investigator: XAVIER DEBUSSCHE, MD CHU DE LA REUNION
PRS Account Centre Hospitalier Universitaire de la Réunion
Verification Date September 2016