- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02898467
Atherothrombosis Markers in Diabetics (MADI)
September 12, 2016 updated by: Centre Hospitalier Universitaire de la Réunion
Comparison of Atherothrombosis Markers From Aortic Atheroma in Diabetic and Non-diabetic Patients
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.
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
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
Enrollment (Anticipated)
100
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: CHRISTINE JUHEL, PHD
- Phone Number: +262262359949
- Email: christine.juhel@chu-reunion.fr
Study Locations
-
-
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Saint Denis de La Réunion, France, 97405
- Department of endocrinology, University Hospital Reunion Island - Felix Guyon Site
-
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
Diabetics and non-diabetics with planned endartectomy
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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
|
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
|
additional blood and urine collection during usual medical care endarterectomy samples during usual medical care
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
On day 1 (day of the surgery)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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On day 1 (day of the surgery)
|
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...)
|
From day 0 (day before the surgery) to day 1 (day of the surgery)
|
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)
|
From day 0 (day before the surgery) to day 1 (day of the surgery)
|
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
|
On day 1 (day of the surgery)
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
From day 0 (day before the surgery) to day 1 (day of the surgery)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: XAVIER DEBUSSCHE, MD, CHU de la Réunion
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2016
Primary Completion (Anticipated)
November 1, 2018
Study Completion (Anticipated)
June 1, 2019
Study Registration Dates
First Submitted
September 8, 2016
First Submitted That Met QC Criteria
September 12, 2016
First Posted (Estimate)
September 13, 2016
Study Record Updates
Last Update Posted (Estimate)
September 13, 2016
Last Update Submitted That Met QC Criteria
September 12, 2016
Last Verified
September 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2013/CHU/06
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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