Platelet Acetyl Coenzyme A Carboxylase Phosphorylation in Coronary Artery Disease

NCT03034148 | Completed

• 1 other identifier: cb07012015
• Study Type: interventional
• Target: 188
• Locations: 1 country
• Sites: 1

Brief Summary

In human purified platelets, only thrombin, and not the other platelet agonists, leads to a transient activation of the protein kinase activated by AMP (AMPK) and to phosphorylation of its "bona fide" substrate, ACC on its Ser79. ACC phosphorylation (P-ACC) can be an interesting marker of thrombin action on platelets. Indeed platelet and coagulation interplay, though undoubtedly present in atherosclerosis and atherothrombosis, remains difficult to assess. Our group showed that atherosclerotic mice (SRBI/Apolipoprotein E knock-out) had higher platelet P-ACC compared to corresponding control mice (C57BL6). In agreement with these data, preliminary results showed increased platelet P-ACC in a small cohort of patients admitted for coronary angiogram, with demonstrated coronary artery disease (CAD). In the light of our preliminary results, we sought to analyze platelet P-ACC in a large prospective clinical trial (ACCTHEROMA) in patients admitted for coronary angiogram. The aim of the study is to compare platelet P-ACC in platelets of patients with CAD and more particularly in unstable CAD patients to non-CAD patients. This study could potentially identify patients at high risk of future ischemic cardiovascular events, because of a higher level of thrombin generation.

Conditions

Coronary Artery Disease; Acute Coronary Syndrome; Coronary Thrombosis

Keywords

Coronary artery disease; Atherothrombosis; Thrombin generation; Platelet Acetyl Coenzyme A carboxylase phosphorylation

Outcome Measures

Primary Outcomes (1)

• an increase in platelet ACC phosphorylation state in patients with coronary artery disease

  2 years

Secondary Outcomes (3)

• a correlation between thrombin generation markers and platelet P-ACC in overall population.

  2 years

• platelet ACC phosphorylation state according clinical severity of CAD (stable versus unstable patients)

  2 years

• the role of platelet P-ACC in predicting the risk of the patient for future cardiovascular events (death, myocardial infarction, stroke)

  3 years

Study Arms (1)

Coronary artery disease

OTHER

blood sampling for biomarkers assessment in a population undergoing coronary angiogram

Diagnostic Test: Platelet Acetyl Coenzyme A Carboxylase analysis in CAD

Interventions

Platelet Acetyl Coenzyme A Carboxylase analysis in CAD DIAGNOSTIC_TEST

Coronary artery disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Planned angiography within the next 3 days, whatever the indication.

You may not qualify if:

• Not able to sign informed consent
• Patients on anticoagulation therapy (oral or parenteral) including heparins, fondaparinux, vitamin K antagonist, novel oral anticoagulants, for any reasons.
• Active neoplasia
• Active inflammatory disease
• Patients with life expectancy lower than 3 years
• Haemophilia and other coagulopathy
• Abnormal platelet count
• Heart transplanted patients
• Active hepatitis B or C or HIV patients
• Any contra-indication for coronary angiography.

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead

Study Sites (1)

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Related Publications (2)

• Onselaer MB, Oury C, Hunter RW, Eeckhoudt S, Barile N, Lecut C, Morel N, Viollet B, Jacquet LM, Bertrand L, Sakamoto K, Vanoverschelde JL, Beauloye C, Horman S. The Ca(2+) /calmodulin-dependent kinase kinase beta-AMP-activated protein kinase-alpha1 pathway regulates phosphorylation of cytoskeletal targets in thrombin-stimulated human platelets. J Thromb Haemost. 2014 Jun;12(6):973-86. doi: 10.1111/jth.12568.

  PMID: 24655923 RESULT

• Robaux V, Kautbally S, Ginion A, Dechamps M, Lejeune S, Menghoum N, Bertrand L, Pouleur AC, Horman S, Beauloye C. Dual antiplatelet therapy is associated with high alpha-tubulin acetylation in circulating platelets from coronary artery disease patients. Platelets. 2023 Dec;34(1):2250002. doi: 10.1080/09537104.2023.2250002.

  PMID: 37700239 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Acute Coronary Syndrome; Coronary Thrombosis; Thrombosis

Interventions

Diagnosis, Computer-Assisted

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Embolism and Thrombosis

Intervention Hierarchy (Ancestors)

Diagnosis

Study Officials

• Christophe Beauloye, MD, PhD

  Cliniques universitaires Saint-Luc- Université Catholique de Louvain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2017
• First Posted: January 27, 2017
• Study Start: March 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: February 17, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)