- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04465591
TROPOnin FRAGMentation in Myocardial Injury Study (Tropo-Fragm)
Troponin T Fragmentation in the Assessment of Myocardial Injury Study
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.
Study Overview
Status
Intervention / Treatment
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, myocarditis and healthy subjects
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Juhani K Airaksinen, MD, PhD
- Phone Number: +358 2 3131005
- Email: juhani.airaksinen@tyks.fi
Study Locations
-
-
Varsinais-suomi
-
Turku, Varsinais-suomi, Finland, 20521
- Recruiting
- Turku University Hospital, Heart Center
-
Contact:
- Juhani KE Airaksinen, MD, PhD
- Phone Number: +358 2 313 1079
- Email: juhani.airaksinen@tyks.fi
-
Contact:
- Samuli Jaakkola, MD, PhD
- Phone Number: +358 2 3138 025
- Email: samuli.jaakkola@tyks.fi
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Principal Investigator:
- Juhani K Airaksinen, MD, PhD
-
Sub-Investigator:
- Saara Wittfooth, PhD
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Sub-Investigator:
- Tapio Hellman, MD, PhD
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Sub-Investigator:
- Samuli Jaakkola, MD, PhD
-
Sub-Investigator:
- Kaj Metsärinne, MD, PhD
-
Sub-Investigator:
- Rami Aalto, MSc
-
Sub-Investigator:
- Kim Pettersson, MD, PhD
-
Sub-Investigator:
- Tuomas Paana, MD
-
-
-
-
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Zürich, Switzerland, 8091 Zurich
- Enrolling by invitation
- University Hospital Zurich
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Troponin T fragmentation sample collected from a recruited patient.
Exclusion Criteria:
- Age <18
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Myocardial infarction
Recruited patients with STEMI or NSTEMI and elevated Troponin T
|
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
|
laboratory test from blood sample
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The fragmentation rate of Troponin T
Time Frame: Baseline
|
The proportion of fragmented Troponin T in patient cohort.
|
Baseline
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Juhani K Airaksinen, MD, PhD, University of Turku
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- T29/2020
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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