Discovery of New Circulating Biomarkers of Coronary Atherosclerosis

December 2, 2010 updated by: Assistance Publique - Hôpitaux de Paris

Discovery of New Circulating Biomarkers of Coronary Atherosclerosis Using Differential Proteomics: the BIOmarkers of CORonary Events (BIOCORE) Study

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Actual)

124

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75018
        • Department of Cardiology, Hopital Bichat, APHP

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 to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

Description

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

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

  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
1
30 patients
Procedure: per intervention
per intervention
2
30 patients
Procedure: per intervention
per intervention
3
30 patients
Procedure: per intervention
per intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Fédération Française de Cardiologie
Société Française de Cardiologie

Investigators

  • Principal Investigator: Laurent FELDMAN, MD,PhD, Assistance Publique - Hopitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

March 1, 2007

Primary Completion (Actual)

July 1, 2009

Study Completion (Actual)

November 1, 2009

Study Registration Dates

First Submitted

February 1, 2007

First Submitted That Met QC Criteria

February 1, 2007

First Posted (Estimate)

February 2, 2007

Study Record Updates

Last Update Posted (Estimate)

December 3, 2010

Last Update Submitted That Met QC Criteria

December 2, 2010

Last Verified

April 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P060201

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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