Discovery of New Circulating Biomarkers of Coronary Atherosclerosis

This study has been completed.
Sponsor:
Collaborators:
Fédération Française de Cardiologie
Société Française de Cardiologie
Information provided by:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00430820
First received: February 1, 2007
Last updated: December 2, 2010
Last verified: April 2009
  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

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

Resource links provided by NLM:


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

Biospecimen Retention:   Samples With DNA

biomarqueurs


Enrollment: 124
Study Start Date: March 2007
Study Completion Date: November 2009
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
Other Name: per intervention
2
30 patients
Procedure: per intervention
per intervention
Other Name: per intervention
3
30 patients
Procedure: per intervention
per intervention
Other Name: 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Yannick Vacher, Department Clinical Research of Developppement
ClinicalTrials.gov Identifier: NCT00430820     History of Changes
Other Study ID Numbers: P060201
Study First Received: February 1, 2007
Last Updated: December 2, 2010
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

Additional relevant MeSH terms:
Atherosclerosis
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Infarction
Myocardial Infarction
Acute Coronary Syndrome
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Heart Diseases
Ischemia
Pathologic Processes
Necrosis
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms

ClinicalTrials.gov processed this record on July 23, 2014