Circulating Markers for Ischemic Heart Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of Connecticut Health Center
Sponsor:
Information provided by (Responsible Party):
Bruce Liang, University of Connecticut Health Center
ClinicalTrials.gov Identifier:
NCT00762333
First received: September 26, 2008
Last updated: January 16, 2013
Last verified: January 2013
  Purpose

The purpose of this research is to determine if two proteins in the blood are increased during acute myocardial infarction and whether their levels are higher in those who develop heart failure than those who do not. These two proteins are produced and potentially released when the heart muscle is damaged. They may then be released into the blood and be detected by standard method in the research laboratory. At this time, detection of an increase in these proteins in the blood is not known to be associated with any disease or myocardial infarction.


Condition
Myocardial Infarction
Ischemia
Congestive Heart Failure

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Circulating Markers for Ischemic Heart Disease

Resource links provided by NLM:


Further study details as provided by University of Connecticut Health Center:

Primary Outcome Measures:
  • Hospitalization for acute myocardial infarction, stroke or death [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

serum


Estimated Enrollment: 500
Study Start Date: June 2007
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Myocardial Infarction

Detailed Description:

Hypotheses, Objectives and Aims:

Hypotheses:Caspase-3, cleaved and activated, and dystrophin can be detected in human circulation. The levels of these two markers are elevated during acute myocardial infarction. Furthermore, the levels of these two proteins are greater in those who develop heart failure than those who do not.

Objectives:

  • To determine whether cleaved caspase-3 and dystrophin can be detected in human circulation after an acute myocardial infarction
  • To compare serum levels of these two markers in those who develop heart failure and those who do not

Scientific Background and Significance: Apoptosis is a regulated biological process resulting in cell death (4-9). Caspases, a family of cysteine acid proteases regulate the process, and in fact, lead to apoptosis. Apoptotic trigger or signal results in the activation of proximal or initiator caspases (such caspase-8, -9, 10). These initiator caspases then cleave and in turn activate downstream effector caspases such as caspases-3, -6 and -7. These effector caspases then cleave various proteins such as those present in cytoskeletons and nucleus like lamin A, alpha-fodrin and poly (ADP-ribose) polymerase, leading to apoptosis. Caspase-3 is the key executioner in this apoptotic pathway, responsible totally or critically in the proteolytic cleavage of cellular and nuclear proteins. Activation of caspase-3 requires proteolytic processing of its inactive zymogen into active p17 and p12 fragments. The cleaved caspase-3 can be detected by antibodies specific for this cleaved enzyme (p17 fragment) in cell lysates by immunoblotting or by an ELISA assay utilizing spectrophotometric determination with a microplate reader at OD450 nm. Ischemia and reperfusion are known to cause apoptosis. Therefore, acute MI may be associated with release of the final executioner of apoptosis that is caspase-3, into the circulation.Another potential marker for acute deterioration is dystrophin. Dystrophin was originally identified as the x-linked gene whose mutations in its N-terminus cause cardiomyopathy. Dystrophin provides important structural support for the cardiac myocyte and its sarcolemmal membrane (10-11). It links actin at its N-terminus with the dystrophin-associated protein complex and sarcolemma at the C-terminus and the extracellular matrix of muscle. Mutations cause loss of support and sarcolemmal instability and myopathy. Myocardial dystrophin translocation and cleavage are associated with the progression of heart failure and contractile dysfunction. These changes are reversed following reduction of mechanical stress from ventricular assistance device (12). Since MI is associated with sarcolemmal instability, dystrophin may also be released into circulation.

  Eligibility

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

There are two arms to this study:

The investigators hope to enroll 350 healthy individuals, as defined by having no prior diagnosis of heart disease to determine baseline levels and diurnal variations of the markers.

Participants being evaluated for an acute Myocardial Infarction as determined by positive CK MB/troponin levels, will be asked to enroll.

Criteria

Inclusion Criteria:

  • men and women, 18 years of age and over with acute myocardial infarction (determined by positive cardiac markers -CKMB/ troponin) with or without heart failure (dyspnea, rales, edema, elevated jugular venous pressure, ascites).
  • Heart failure can be diagnosed using imaging evidence such as dilated heart, poor contractile function or echocardiographic Doppler evidence of diastolic dysfunction or elevated right- or left-sided filling pressures
  • A control group of male subjects age 60 and older without history of MI or heart disease

Exclusion Criteria:

  • Subjects unable to give consent
  • Subjects who have undergone cardiac or non-cardiac surgery in the 3 months prior to enrollment
  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: NCT00762333

Contacts
Contact: Jayne M. Schumacher, RN 860-679-2692 schumacher@uchc.edu

Locations
United States, Connecticut
University of Connecticut Health Center Recruiting
Farmington, Connecticut, United States, 06030
Principal Investigator: Bruce T. Liang, MD         
Sponsors and Collaborators
University of Connecticut Health Center
Investigators
Principal Investigator: Bruce T. Liang, MD University of Connecticut Health Center
  More Information

No publications provided

Responsible Party: Bruce Liang, Professor of Medicine, Director Pat and Jim Calhoun Cardiovascular Center, University of Connecticut Health Center
ClinicalTrials.gov Identifier: NCT00762333     History of Changes
Other Study ID Numbers: 07-252-2, 59806
Study First Received: September 26, 2008
Last Updated: January 16, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Heart Failure
Myocardial Infarction
Infarction
Heart Diseases
Coronary Artery Disease
Myocardial Ischemia
Cardiovascular Diseases
Vascular Diseases
Ischemia
Pathologic Processes
Necrosis
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases

ClinicalTrials.gov processed this record on October 19, 2014