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TROPOnin FRAGMentation in Myocardial Injury Study (Tropo-Fragm)

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ClinicalTrials.gov Identifier: NCT04465591
Recruitment Status : Recruiting
First Posted : July 10, 2020
Last Update Posted : July 10, 2020
Sponsor:
Information provided by (Responsible Party):
Juhani Airaksinen, University of Turku

Brief Summary:

Troponin T (TnT) is a part of the troponin protein complex that principally exists in cardiac and skeletal muscle cells and is widely used as diagnostic biomarker for myocardial injury and, thus, myocardial infarction (MI). Elevated TnT levels can, however, be observed in the presence of other clinical conditions such as heart failure, sepsis and kidney failure and the contemporary high-sensitivity TnT test may yield false positive results when performing diagnostics for suspected MI in these patients.

Recent data have demonstrated that in the presence of MI, TnT gradually undergoes fragmentation into smaller fragments. It has been suggested that in the presence of e.g. chronic kidney disease or physical exercise the released TnT is predominantly in the form of smaller fragments.

However, the clinical significance of TnT fragmentation is unknown and, thus, we sought to investigate the prevalence of fragmentation of TnT in different patient cohorts.


Condition or disease Intervention/treatment
Acute Myocardial Infarction Type 1 Myocardial Injury Diagnostic Test: troponin T fragmentation test

Detailed Description:

Modern cardiac troponin T (cTnT) tests are highly sensitive in diagnosing AMI and myocardial damage. Atrial fibrillation and many non-cardiac conditions and even strenuous exercise are associated with elevated cTnT levels which are problematic to clinicians and may lead to redundant use of diagnostic coronary angiography or "overdiagnosis" of ACS in the emergency room workup.

The cardiac troponin (cTn) complex is part of the thin filaments of myocardium. Small part (approximately 5% of total content) of troponins are cytosolic. These smaller cytosolic fragments may more easily traverse across cell membranes that have become leaky for some reason but not irreversibly damaged. Only cytoplasmic forms of troponin are contained in the subcellular blebs which lyse upon early cTn release into the circulation. Bleb formation may explain how troponin can appear in blood in the absence of cell necrosis. Still many aspects of their intramyocardial degradation, their tissue release, and their degradation within and elimination from the human circulation are still incompletely understood.

In the early hours of AMI, troponin is found in its full-size complex, but the complexed cTnT degrades in a time-dependent pattern after the first hours. Small molecular weight troponin fragments originating from the cytoplasm may traverse across leaky cell membranes not completely damaged in various conditions without irreversible myocardial cell necrosis.

Commercial cTnT test detects all these fragments and may thus lead to false diagnosis of AMI. At present, there is limited information based on small studies using complicated gel filtration chromatography and Western blotting showing cTnT fragmentation in later phases of AMI and in renal failure. These time-consuming analytical methods are, however, not suitable for clinical purposes in the emergency room.

ANALYTICAL METHODS In this study we test a novel sensitive time-resolved immunofluorometric assay, which has been developed at the biotechnology unit of the Department Biochemistry, University of Turku, which enables us to measure cTnT from blood samples in its intact or only slightly fragmented form. Thus, we can exclude the highly fragmented short forms of cTnT from the analysis. This selectivity can be achieved with specific capture and tracer antibodies that bind to carefully chosen epitopes located closer to the opposite ends of the cTnT molecule. In the assay one of the antibodies is attached to a surface and acts as an antigen capturing antibody. The capture-antigen pair can be detected with tracer antibody, thus forming capture-antigen-tracer complex. In our case this tracer antibody has been labeled with europium chelates which provide sensitive detection by time-resolved fluorometry.

The aim of Tropo-Fragment study is to use the described preliminary assay format in the clinical studies to evaluate:

  • TnT fragmentation and its time course in STEMI and NSTEMI
  • TnT fragmentation in renal failure, sepsis, strenuous exercise, stroke, atrial fibrillation, takotsubo and myocarditis

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 600 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Target Follow-Up Duration: 1 Day
Official Title: Troponin T Fragmentation in the Assessment of Myocardial Injury Study
Actual Study Start Date : April 2, 2020
Estimated Primary Completion Date : December 30, 2021
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

Group/Cohort Intervention/treatment
Myocardial infarction
Recruited patients with STEMI or NSTEMI and elevated Troponin T
Diagnostic Test: troponin T fragmentation test
laboratory test from blood sample

Myocardial injury
Recruited patients with myocardial injury based on elevated Troponin T and associated with renal failure, severe infection, strenouos exercise, atrial fibrillation, myocarditis, takotsubo cardiomyopathy or other similar conditions
Diagnostic Test: troponin T fragmentation test
laboratory test from blood sample




Primary Outcome Measures :
  1. The fragmentation rate of Troponin T [ Time Frame: Baseline ]
    The proportion of fragmented Troponin T in patient cohort.


Biospecimen Retention:   Samples Without DNA

Heparin plasma:

  • Troponin T control sample
  • Troponin T fragmentation sample


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients are prospectively recruited from the Heart Center, Department of Medicine and Kidney Center of the study hospital. All patients aged 18 years are eligible.
Criteria

Inclusion Criteria:

  • Troponin T fragmentation sample collected from a recruited patient.

Exclusion Criteria:

  • Age <18

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04465591


Contacts
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Contact: Juhani K Airaksinen, MD, PhD +358 2 3131005 juhani.airaksinen@tyks.fi

Locations
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Finland
Turku University Hospital, Heart Center Recruiting
Turku, Varsinais-suomi, Finland, 20521
Contact: Juhani KE Airaksinen, MD, PhD    +358 2 313 1079    juhani.airaksinen@tyks.fi   
Contact: Samuli Jaakkola, MD, PhD    +358 2 3138 025    samuli.jaakkola@tyks.fi   
Principal Investigator: Juhani K Airaksinen, MD, PhD         
Sub-Investigator: Saara Wittfooth, PhD         
Sub-Investigator: Tapio Hellman, MD, PhD         
Sub-Investigator: Samuli Jaakkola, MD, PhD         
Sub-Investigator: Kaj Metsärinne, MD, PhD         
Sub-Investigator: Rami Aalto, MSc         
Sub-Investigator: Tuomas Paana, MD         
Sub-Investigator: Kim Pettersson, MD, PhD         
Sponsors and Collaborators
University of Turku
Investigators
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Principal Investigator: Juhani K Airaksinen, MD, PhD University of Turku
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Responsible Party: Juhani Airaksinen, Professor, University of Turku
ClinicalTrials.gov Identifier: NCT04465591    
Other Study ID Numbers: T/
First Posted: July 10, 2020    Key Record Dates
Last Update Posted: July 10, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Juhani Airaksinen, University of Turku:
Troponin
myocardial injury
myocardial infarction
Additional relevant MeSH terms:
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Myocardial Infarction
Infarction
Wounds and Injuries
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases