Ignite Creation Date:
2024-05-06 @ 9:38 AM
Last Modification Date:
2024-10-26 @ 12:17 PM
Study NCT ID:
NCT03034148
Status:
COMPLETED
Last Update Posted:
2017-02-17
First Post:
2017-01-25
Brief Title:
Platelet Acetyl Coenzyme A Carboxylase Phosphorylation in Coronary Artery Disease
Sponsor:
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Organization:
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Study Overview
Official Title:
Prospective Evaluation of Acetyl-Coenzyme A Carboxylase Phosphorylation State in Platelets in Atherothrombotic Coronary Artery Disease
Status:
COMPLETED
Status Verified Date:
2017-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ACCTHEROMA
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 SRBIApolipoprotein 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
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
Detailed Description:
Consecutive patients with planned coronary angiogram at the Cliniques Universitaires Saint Luc Brussels whatever the indication will be included between March 2015 and February 2016 Informed consent will be obtained before angiogram
A Blood Sampling Routine veinous blood sample will be done under fasting condition in the cardiology ward before the angiogram standard of care for patients undergoing coronary angiogram
In order to avoid additional puncture for blood sampling and to limit platelet activation blood samples are withdrawn after sheath insertion at the Cath lab before any drug administration The following measurements will be done
Routine coagulation tests including international rationalize ratio activated cephaline time thrombin time prothrombin time Fibrinogen DDimers
Platelet reactivity testing by the Multiple Electrode Aggregometer Multiplate Analysis
Platelet isolation and lysates will be stocked frozen for phospho-protein analysis by immunoblotting and electrochemiluminescence ECLIA
Aliquots of poor platelet plasma stocked frozen for inflammation HsCRP thrombin generation tests thrombin-antithrombin complex prothrombin fragment F12 endogenous thrombin generation potential-ETP platelet activation markers platelet factor 4 soluble CD40ligand soluble P-selectin and circulating micro-RNA extraction
Platelet isolation and further purification for platelet specific micro-RNA extraction
B Atherosclerosis evaluation All patients underwent coronary angiogram Significant coronary artery lesion is defined as a luminal stenosis above 50 Syntax score will be calculated for all patients
Global atherosclerotic plaque burden on coronary and extracoronary arteries will be evaluated by measuring calcium score on thoraco-abdominal scanner with prospective ECG-gating in a randomly selected subgroup of patients Coronary artery calcification CAC is expressed as Agatston score using calcium scoring software Philips Healthcare with a threshold of 130 Hounsfield units The degree of atherosclerotic burden on coronary arteries is classified as mild Agatston score 100 moderate Agatston score 100-400 or severe Agatston score 400 Aortic calcification AoC score was measured from aortic arch to iliac arteries in all patients
C Data collection Baseline characteristics of patients will be collected from the medical database of the Cliniques Universitaires Saint Luc All coronary angiogram will be reviewed by 2 different investigators and syntax score will be calculated with the online syntax score calculator CAC Agatston and AoC score will also be assessed by 2 different investigators
DPatients Classification for platelet P-ACC analysis Platelet ACC phosphorylation P-ACC analysis will be done by immunoblotting with a specific antibody probing for phosphorylated Ser 79 ACC Purified washed platelets stimulated with 05 unitsml thrombin will be used as positive internal controls
Patients will first be classified in non-CAD and CAD groups based on the results of coronary angiogram and CAC Agatston score Non-CAD absence of lesion on angiogram andor CAC Agatston score100 and CAD presence of at least 1 lesion on angiogram andor CAC Agatston score100
In a second analysis based on clinical presentation the CAD group will further be divided into Stable CAD or Unstable CAD acute coronary syndrome ACS Platelet P-ACC will be compared in both subgroups This detailed classification will outline high-risk patients with ongoing acute coronary syndrome
E Sample size and statistical analysis Based on our preliminary data we determined that enrolment of 102 patients would provide a power of 80 at a significance level of 5 to detect a difference of 015 AU in the phosphorylation of ACC in atherosclerotic patients compared to non CAD patients
Continuous variables will be expressed as mean - one standard deviation categoric variables as counts and percentages Patients will separated in four groups depending on the level of P-ACC quartiles Clinical presentation thrombin generation markers and calcium scoring will be compared in all these groups based on ANOVA analysis Variables will be submitted to logistic regression test in order to identify independent predictors of high ACC phosphorylation state The role of high platelets P-ACC in assessing the risk of the patients will be then studied
FFollow-up A follow-up period of 3 years is planned Events recorded during the follow-up period will be obtained from the medical database and a phone call will be done in case of missing data
A Blood Sampling Routine veinous blood sample will be done under fasting condition in the cardiology ward before the angiogram standard of care for patients undergoing coronary angiogram
In order to avoid additional puncture for blood sampling and to limit platelet activation blood samples are withdrawn after sheath insertion at the Cath lab before any drug administration The following measurements will be done
Routine coagulation tests including international rationalize ratio activated cephaline time thrombin time prothrombin time Fibrinogen DDimers
Platelet reactivity testing by the Multiple Electrode Aggregometer Multiplate Analysis
Platelet isolation and lysates will be stocked frozen for phospho-protein analysis by immunoblotting and electrochemiluminescence ECLIA
Aliquots of poor platelet plasma stocked frozen for inflammation HsCRP thrombin generation tests thrombin-antithrombin complex prothrombin fragment F12 endogenous thrombin generation potential-ETP platelet activation markers platelet factor 4 soluble CD40ligand soluble P-selectin and circulating micro-RNA extraction
Platelet isolation and further purification for platelet specific micro-RNA extraction
B Atherosclerosis evaluation All patients underwent coronary angiogram Significant coronary artery lesion is defined as a luminal stenosis above 50 Syntax score will be calculated for all patients
Global atherosclerotic plaque burden on coronary and extracoronary arteries will be evaluated by measuring calcium score on thoraco-abdominal scanner with prospective ECG-gating in a randomly selected subgroup of patients Coronary artery calcification CAC is expressed as Agatston score using calcium scoring software Philips Healthcare with a threshold of 130 Hounsfield units The degree of atherosclerotic burden on coronary arteries is classified as mild Agatston score 100 moderate Agatston score 100-400 or severe Agatston score 400 Aortic calcification AoC score was measured from aortic arch to iliac arteries in all patients
C Data collection Baseline characteristics of patients will be collected from the medical database of the Cliniques Universitaires Saint Luc All coronary angiogram will be reviewed by 2 different investigators and syntax score will be calculated with the online syntax score calculator CAC Agatston and AoC score will also be assessed by 2 different investigators
DPatients Classification for platelet P-ACC analysis Platelet ACC phosphorylation P-ACC analysis will be done by immunoblotting with a specific antibody probing for phosphorylated Ser 79 ACC Purified washed platelets stimulated with 05 unitsml thrombin will be used as positive internal controls
Patients will first be classified in non-CAD and CAD groups based on the results of coronary angiogram and CAC Agatston score Non-CAD absence of lesion on angiogram andor CAC Agatston score100 and CAD presence of at least 1 lesion on angiogram andor CAC Agatston score100
In a second analysis based on clinical presentation the CAD group will further be divided into Stable CAD or Unstable CAD acute coronary syndrome ACS Platelet P-ACC will be compared in both subgroups This detailed classification will outline high-risk patients with ongoing acute coronary syndrome
E Sample size and statistical analysis Based on our preliminary data we determined that enrolment of 102 patients would provide a power of 80 at a significance level of 5 to detect a difference of 015 AU in the phosphorylation of ACC in atherosclerotic patients compared to non CAD patients
Continuous variables will be expressed as mean - one standard deviation categoric variables as counts and percentages Patients will separated in four groups depending on the level of P-ACC quartiles Clinical presentation thrombin generation markers and calcium scoring will be compared in all these groups based on ANOVA analysis Variables will be submitted to logistic regression test in order to identify independent predictors of high ACC phosphorylation state The role of high platelets P-ACC in assessing the risk of the patients will be then studied
FFollow-up A follow-up period of 3 years is planned Events recorded during the follow-up period will be obtained from the medical database and a phone call will be done in case of missing data
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None