Discovery of New Circulating Biomarkers of Coronary Atherosclerosis - Full Text View

Sponsors and Collaborators:	Assistance Publique - Hôpitaux de Paris Fédération Française de Cardiologie Société Française de Cardiologie
Information provided by:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00430820

Purpose

The study hypothesis is that differential proteomic techniques can be used to discover new circulating biomarkers of coronary atherosclerosis in the blood of patients suffering from coronary artery disease (either stable or unstable) who will be compared to a group of patients without coronary artery disease

Condition	Intervention
Coronary Artery Disease Acute Coronary Syndromes Myocardial Infarction Atherosclerosis	Procedure: per intervention

MedlinePlus related topics: Coronary Artery Disease Heart Attack

U.S. FDA Resources

Study Type:	Observational
Study Design:	Prospective
Official Title:	Discovery of New Circulating Biomarkers of Coronary Atherosclerosis Using Differential Proteomics: the BIOmarkers of CORonary Events (BIOCORE) Study

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Biospecimen Retention: Samples With DNA

Biospecimen Description:

biomarqueurs

Estimated Enrollment:	124
Study Start Date:	March 2007
Estimated Study Completion Date:	November 2009
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
1 30 patients	Procedure: per intervention per intervention
2 30 patients	Procedure: per intervention per intervention
3 30 patients	Procedure: per intervention per intervention

Detailed Description:

Hypothesis: Our hypothesis is that coronary atherosclerosis induces both quantitative and qualitative modifications of circulating proteins, which can be captured by a differential proteomic approach applied to serum or plasma samples. Identification of such modifications in the circulating blood of patients with coronary artery disease (versus patients without coronary artery disease) and/or of patients with acute coronary syndromes (versus stable coronary artery disease) may lead to discovery of new biomarkers of coronary atherosclerosis and of atherosclerotic plaque vulnerability.

Objectives:

Primary objective: Identification of new circulating biomarkers of stable and unstable coronary artery disease using a new approach of differential proteomics.

Secondary objectives:

Evaluation of the diagnostic value of these new biomarkers for the diagnosis of stable and unstable coronary artery disease.
Comparison of the diagnostic value of these new biomarkers to the diagnostic value of 1) other validated biomarkers of atherosclerosis (eg, CRP, IL-6, CD40L, markers of leukocyte activation, …); and 2) of non-invasive measures of arterial function (eg, carotid artery intima-media thickness, pulse wave velocity, ankle/brachial index, …)
Description of the relationship between these new biomarkers and major adverse coronary events (death, myocardial infarction, revascularization) during a 12-month follow-up.

Methods:

Uniq center, prospective study. Three groups of patients will be studied. Group 1: Non-ST-elevation acute myocardial infarction; Group 2: Stable coronary artery disease; Group 3: normal coronary arteries and absence of other detectable atherosclerotic lesions.

A new proteomic approach will be applied to serum and plasma samples obtained 1 month after the index hospitalisation. This approach includes 3 steps: 1) equalisation of circulating proteins (expose low-concentration proteins belonging to the "deep-proteome"); 2) Retention chromatography; and 3) protein separation using 2D-electrophoresis and Surface-Enhanced Laser Desorption/Ionisation Time-of-Flight (SELDI-TOF).

Biomarkers with the highest diagnostic value will be subsequently identified using Matrix-Assisted Laser Desorbtion/Ionisation Time-of-Flight (MALDI-TOF) and tandem mass spectrometry (MS/MS).

Perspectives:

Validation of the diagnostic and prognostic values of the new biomarkers discovered and identified using the proteomic approach described above will require development of more straightforward measurement techniques (eg, ELISA), which will be used prospectively or retrospectively in other cohorts of patients with coronary artery disease. Basic studies will be performed in parallel, so as to better understand the role of these new biomarkers in the pathophysiology of atherosclerosis.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

Identification de nouveaux marqueurs circulants de l'athérosclérose coronarienne et de ses complications par une nouvelle technique de protéomique différentielle. Identification of new parqueurs circulated in coronary artheriosclerosis and complications of the new differentiel technicology

Criteria

Inclusion Criteria:

Group 1 (Non-ST-elevation acute myocardial infarction) :
- Chest pain less than 48 hours before admission,
- And modifications of ST-T (no persistent ST elevation) on 12-lead EKG,
- And elevation of troponin-I >1xN,
- And presence of ≥1 de novo stenosis(es) >50% located on ≥1 native coronary artery(ies) and successfully treated using percutaneous coronary intervention and stenting.
Group 2 (Stable coronary artery disease) :
- Documented myocardial ischemia (stable angina or positive stress test)
- And presence of ≥1 de novo stenosis(es) >50% located on ≥1 native coronary artery(ies) and successfully treated using percutaneous coronary intervention and stenting.
Group 3 (Normal coronary arteries) :
- No history of coronary artery disease, neurovascular disease or peripheral artery disease,
- And normal coronary angiography performed because of suspected coronary artery disease
- And absence of significant functional or anatomic abnormalities suggestive of atherosclerosis on non-invasive arterial studies (measurements of intima-media thickness, pulse wave velocity, ankle-brachial index, …).

Exclusion Criteria:

Group 1 :
- Preexisting EKG abnormalities (including left bundle branch block) precluding accurate assessment of ST-T changes
Group 2 :
- History of acute coronary syndrome
Groups 1 and 2:
- Culprit coronary artery stenosis is a restenosis or a stent thrombosis or is located in a bypass graft.
All groups :
- Heart failure (NYHA class ≥II)
- Left ventricular ejection fraction <50%
- Severe valvular heart disease requiring surgical or percutaneous therapy
- History of autoimmune, inflammatory or neoplasia diseases ; or infectious disease in the month before admission
- Life expectancy < 1 year
- Age <18 years or >80 years
- Current pregnancy or breast-feeding
- Homeless or travelers who may not be followed-up
- Refusal to sign the informed consent form

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00430820

Locations

France
Department of Cardiology, Hopital Bichat, APHP
PARIS, France, 75018

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Fédération Française de Cardiologie

Société Française de Cardiologie

Investigators

Principal Investigator:

Laurent FELDMAN, MD,PhD

Assistance Publique - Hôpitaux de Paris

More Information

Publications:

Duran MC, Mas S, Martin-Ventura JL, Meilhac O, Michel JB, Gallego-Delgado J, Lazaro A, Tunon J, Egido J, Vivanco F. Proteomic analysis of human vessels: application to atherosclerotic plaques. Proteomics. 2003 Jun;3(6):973-8.

Martin-Ventura JL, Duran MC, Blanco-Colio LM, Meilhac O, Leclercq A, Michel JB, Jensen ON, Hernandez-Merida S, Tunon J, Vivanco F, Egido J. Identification by a differential proteomic approach of heat shock protein 27 as a potential marker of atherosclerosis. Circulation. 2004 Oct 12;110(15):2216-9. Epub 2004 Jul 12.

Vivanco F, Martin-Ventura JL, Duran MC, Barderas MG, Blanco-Colio L, Darde VM, Mas S, Meilhac O, Michel JB, Tunon J, Egido J. Quest for novel cardiovascular biomarkers by proteomic analysis. J Proteome Res. 2005 Jul-Aug;4(4):1181-91. Review.

Blanco-Colio LM, Martin-Ventura JL, Vivanco F, Michel JB, Meilhac O, Egido J. Biology of atherosclerotic plaques: what we are learning from proteomic analysis. Cardiovasc Res. 2006 Oct 1;72(1):18-29. Epub 2006 May 24.

Responsible Party:	Department Clinical Research of Developppement ( Yannick Vacher )
Study ID Numbers:	P060201
Study First Received:	February 1, 2007
Last Updated:	April 1, 2009
ClinicalTrials.gov Identifier:	NCT00430820 History of Changes
Health Authority:	France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Biomarkers
Proteomics
Mass spectrometry
Atherosclerosis

Acute coronary syndromes
Myocardial infarction
Coronary artery disease

Study placed in the following topic categories:

Atherosclerosis
Arterial Occlusive Diseases
Heart Diseases
Myocardial Ischemia
Vascular Diseases
Arteriosclerosis
Ischemia

Coronary Disease
Necrosis
Acute Coronary Syndrome
Infarction
Myocardial Infarction
Coronary Artery Disease

Additional relevant MeSH terms:

Atherosclerosis
Arterial Occlusive Diseases
Disease
Heart Diseases
Myocardial Ischemia
Vascular Diseases
Ischemia
Arteriosclerosis
Coronary Disease

Necrosis
Pathologic Processes
Syndrome
Acute Coronary Syndrome
Cardiovascular Diseases
Infarction
Myocardial Infarction
Coronary Artery Disease

ClinicalTrials.gov processed this record on May 07, 2009