DiabetesMADINCT02898467
Atherothrombosis Markers in Diabetics
An observational study of Diabetes and Atherothrombosis, run by Centre Hospitalier Universitaire de la Réunion at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes, Atherothrombosis, Cardiovascular Disease
- What is being tested?
- diabetics and non-diabetics
- Type of treatment
- Pill or oral medicine
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- Oct 2016to Jun 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Diabetics and non-diabetics with planned endartectomy
Who may be able to join
- Adult patients with planned endarterectomy
- Affiliated to social security rights
- Signed inform consent
Who cannot join
- pregnancy
- Autoimmune disease, chronic inflammatory disease, neoplasia
- Type 1 diabetes
Trial locations and contacts
1 site in 1 country.
France1 site
Department of endocrinology, University Hospital Reunion Island - Felix Guyon Site
Saint Denis de La Réunion, 97405
About this study
Official title: 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.
Read the 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
- Being tested
- diabetics, non-diabetics
- Medical subject headings
- Diabetes Mellitus, Thrombosis, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
diabeticsOther
additional blood and urine collection during usual medical care endarterectomy samples during usual medical care
non-diabeticsOther
additional blood and urine collection during usual medical care endarterectomy samples during usual medical care
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Other: diabetics | |
| non-diabetics | patients without diagnosed diabetes exhibiting fasting glycemia value under 7 mmol/L Receives: Other: non-diabetics |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: On day 1 (day of the surgery)
Secondary outcomes (4)
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
Measured: On day 1 (day of the surgery)
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...)
Measured: From day 0 (day before the surgery) to day 1 (day of the surgery)
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)
Measured: From day 0 (day before the surgery) to day 1 (day of the surgery)
Atherothrombosis characterization assessed by histological analysis
Histological characterization of plaques assessed by quantification of neovessels, calcification, lipids composition
Measured: On day 1 (day of the surgery)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2016 (estimated)
- Study startOct 2016
- Primary completionNov 2018 (estimated)
- Study completionJun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de la Réunion
- Sponsor type
- University, hospital or other
- Collaborators
- Academic Health Science Centres
- Responsible party
- Sponsor
- Investigators
- XAVIER DEBUSSCHE, MD, Principal investigator, CHU DE LA REUNION
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02898467
- Sponsor's protocol ID
- 2013/CHU/06
- Acronym
- MADI
- Status last verified
- Sep 2016
- First submitted
- 8 Sep 2016
- Last updated
- 13 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Atherothrombosis Markers From Aortic Atheroma in Diabetic and Non-diabetic Patients
- ClinicalTrials.gov ID
- NCT02898467
- Acronym / sponsor ID
- MADI / 2013/CHU/06
- Conditions
- Diabetes, Atherothrombosis, Cardiovascular Disease
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire de la RéunionUniversity, hospital or other
- Collaborators
- Academic Health Science Centres
- Study start
- Oct 2016
- Primary completion
- Nov 2018 (estimated)
- Study completion
- Jun 2019 (estimated)
- First posted
- 13 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| diabetics | – | Other: diabeticsType 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 |
| non-diabetics | – | Other: non-diabeticspatients without diagnosed diabetes exhibiting fasting glycemia value under 7 mmol/L |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Diabetics and non-diabetics with planned endartectomy
Key inclusion criteria (3 listed)
- Adult patients with planned endarterectomy
- Affiliated to social security rights
- Signed inform consent
Key exclusion criteria (3 listed)
- pregnancy
- Autoimmune disease, chronic inflammatory disease, neoplasia
- Type 1 diabetes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| diabeticsadditional blood and urine collection during usual medical care endarterectomy samples during usual medical care | Other | diabetics |
| non-diabeticsadditional blood and urine collection during usual medical care endarterectomy samples during usual medical care | Other | non-diabetics |
Primary outcome
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
4 secondary outcomes
Neutrophile activation assessed by other makers than free DNA levels in atherothrombotic plaques
Time frame: 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)
Correlation between plasma and atherothrombotic plaque markers assessement
Time frame: 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)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2016.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
XAVIER DEBUSSCHE, MD principal investigator
CHU DE LA REUNION
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes and Atherothrombosis, run by Centre Hospitalier Universitaire de la Réunion at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact CHRISTINE JUHEL, PHD (+262262359949, christine.juhel@chu-reunion.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neutrophile activation assessed by free DNA levels in atherothrombotic plaques (time frame: On day 1 (day of the surgery)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2016.