Thrombin Regulated Platelet Activation

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by Vanderbilt University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00855296
First received: March 2, 2009
Last updated: June 29, 2011
Last verified: June 2011
  Purpose

Thrombin is the most potent activator of platelets, and platelet activation is a hallmark of thrombosis. Coronary artery disease (CAD) is the major cause of mortality and morbidity in the United States and other industrialized countries, and thrombotic sequelae are the key cause of death in diabetes. The accumulation of thrombin at sites of vascular injury provides one of the major mechanisms of recruiting platelets into a hemostatic plug. Thrombin works by activation of the G protein-coupled protease activated receptors PAR1 and PAR4 on human platelets to initiate signaling cascades leading to increases in [Ca]i, secretion of autocrine activators, trafficking of adhesion molecules to the plasma membrane, and shape change, which all promote platelet aggregation. The thrombin receptors work in a progressive manner, with PAR1 activated at low thrombin concentrations, and PAR4 recruited at higher thrombin concentrations. As direct thrombin inhibitors become widely used in clinical practice, it is important to assess their effects on vascular function. Our hypothesis is that PAR1 and PAR4 do not signal through the same G protein pathways, and that PAR4 is not a strong platelet agonist. To investigate this hypothesis, the investigators will study the G protein pathways downstream of PAR4, and assess ex-vivo platelet responsiveness to thrombin, PAR1, and PAR4 agonist peptides, both in normal human subjects, and along the stages of pathology, from patients with stable angina as well as unstable angina who are undergoing angioplasty. Similarly, the investigators will examine platelet function in patients with metabolic syndrome as well as diabetes, along the continuum from insulin resistance to full-blown disease. These studies will provide deeper insight into the G protein pathways used by PARs. They will elucidate the contribution of PAR receptors to normal platelet function as well as the abnormal platelet activation in thrombotic states. The long term goal is to understand the implications for PAR receptors as therapeutic targets for anti-platelet therapies that may carry less bleeding risk.


Condition
Coronary Artery Disease
Acute Coronary Syndrome

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Thrombin Regulated Platelet Activation

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Biospecimen Retention:   Samples With DNA

Whole blood


Estimated Enrollment: 200
Study Start Date: September 2006
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Patients undergoing angioplasty

Criteria

Inclusion Criteria:

  • Age: over 18, Sex: male and female.
  • Patients who undergo clinically indicated coronary angiography and/or PCI. Patients in Group 1 (elective PCI) include those presented with stable angina (ACC definition for stable angina).
  • Coronary angiography reveals severe stenosis (>70%) that requires PCI.
  • Patients in Group 2 (elective PCI in subjects with diabetes) include those who present with stable angina, or with findings on non-invasive testing (exercise or pharmacologic stimulation with imaging by nuclear perfusion imaging or stress echocardiography) in whom coronary angiography reveals severe stenosis (>70%) that requires PCI.
  • Patients in Group 2 (ACS) include those presented with unstable angina or non-ST elevation myocardial infarction (as defined by the ACC).
  • Coronary angiography reveals severe stenosis (>70%) that requires PCI.

Exclusion Criteria:

  • Significant left main coronary artery disease.
  • Severely impaired left ventricular systolic function (EF<35%).
  • Prior treatment with enoxaparin, Bivalirudin (or other thrombin inhibitors), Warfarin, or thrombolytic agents <48 hours.
  • Prior history of myocardial infarction (<6 weeks). Prior history of stroke (<6 weeks).
  • Prior history of coronary intervention (<6 weeks).
  • History of HIV/AIDS.
  • The patients will be identified in the following manner:
  • All subjects will be picked from a pool of patients diagnosed with stable angina and diabetes from the Vanderbilt Page-Campbell Heart Institute at Vanderbilt University Medical Center and undergo a complete history and physical examination.
  • Patients with acute coronary syndrome will be referred from the acute cardiology patient service at Vanderbilt University Medical Center.
  • Subjects with hematologic, renal (creatinine > 2.0 mg/dl), hepatic, inflammatory, and neoplastic disorders, and those who sustained a recent (< 1 month) myocardial infarction, ACS, or stroke will be excluded. Patients who used nonsteroidal anti-inflammatory drugs, corticosteroids, or hormone replacement therapy will also be excluded.
  • Pregnancy will be excluded in women of child bearing potential by measurement of urine ß-HCG (it is standard of care to determine if a woman is pregnant prior to elective PCI and will be screened as part of their PHI).
  • For healthy volunteers, pregnancy will be excluded per verbal report.
  • Data will be collected regarding patient demographics including height and weight, abdominal circumference, blood pressure, comorbid medical conditions, triglycerides, HDL, fasting glucose and medication use (including prescription of antithrombotic agents, ACE inhibitors, angiotensin receptor blockers, beta blockers, calcium channel antagonists and HMG-CoA inhibitors).
  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: NCT00855296

Contacts
Contact: Nancy Colowick, M.Ed. 615-322-5268 nancy.e.colowick@vanderbilt.edu
Contact: Matthew Duvernay, Ph.D. 615-322-5268 matthew.t.duvernay@Vanderbilt.Edu

Locations
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Nancy Colowick, M.Ed.    615-322-5268    nancy.e.colowick@vanderbilt.edu   
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Heidi E. Hamm, Ph.D. Vanderbilt Universtiy Medical Center, Pharmacology
  More Information

No publications provided

Responsible Party: Heidi E. Hamm, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00855296     History of Changes
Other Study ID Numbers: 050182
Study First Received: March 2, 2009
Last Updated: June 29, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Acute Coronary Syndrome
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms
Thrombin
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014