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Circulating Markers for Ischemic Heart Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT00762333
Recruitment Status : Recruiting
First Posted : September 30, 2008
Last Update Posted : March 5, 2021
Information provided by (Responsible Party):
Bruce Liang, UConn Health

Tracking Information
First Submitted Date September 26, 2008
First Posted Date September 30, 2008
Last Update Posted Date March 5, 2021
Study Start Date June 2007
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: September 26, 2008)
Hospitalization for acute myocardial infarction, stroke or death [ Time Frame: 3 years ]
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title Circulating Markers for Ischemic Heart Disease
Official Title Circulating Markers for Ischemic Heart Disease
Brief Summary 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.
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.


  • 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.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
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.

  • Myocardial Infarction
  • Ischemia
  • Congestive Heart Failure
Intervention Not Provided
Study Groups/Cohorts Myocardial Infarction
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: October 5, 2016)
Original Estimated Enrollment
 (submitted: September 26, 2008)
Estimated Study Completion Date March 2022
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Eligibility 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
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contact: Sharon B. DiMauro, MA 860-679-2692
Listed Location Countries United States
Removed Location Countries  
Administrative Information
NCT Number NCT00762333
Other Study ID Numbers 07-252-2
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Bruce Liang, UConn Health
Study Sponsor UConn Health
Collaborators Not Provided
Principal Investigator: Bruce T. Liang, MD UConn Health
PRS Account UConn Health
Verification Date March 2021