<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04465591</url>
  </required_header>
  <id_info>
    <org_study_id>T29/2020</org_study_id>
    <nct_id>NCT04465591</nct_id>
  </id_info>
  <brief_title>TROPOnin FRAGMentation in Myocardial Injury Study</brief_title>
  <acronym>Tropo-Fragm</acronym>
  <official_title>Troponin T Fragmentation in the Assessment of Myocardial Injury Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Turku</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Turku</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Troponin T (TnT) is a part of the troponin protein complex that principally exists in cardiac&#xD;
      and skeletal muscle cells and is widely used as diagnostic biomarker for myocardial injury&#xD;
      and, thus, myocardial infarction (MI). Elevated TnT levels can, however, be observed in the&#xD;
      presence of other clinical conditions such as heart failure, sepsis and kidney failure and&#xD;
      the contemporary high-sensitivity TnT test may yield false positive results when performing&#xD;
      diagnostics for suspected MI in these patients.&#xD;
&#xD;
      Recent data have demonstrated that in the presence of MI, TnT gradually undergoes&#xD;
      fragmentation into smaller fragments. It has been suggested that in the presence of e.g.&#xD;
      chronic kidney disease or physical exercise the released TnT is predominantly in the form of&#xD;
      smaller fragments.&#xD;
&#xD;
      However, the clinical significance of TnT fragmentation is unknown and, thus, we sought to&#xD;
      investigate the prevalence of fragmentation of TnT in different patient cohorts.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Modern cardiac troponin T (cTnT) tests are highly sensitive in diagnosing AMI and myocardial&#xD;
      damage. Atrial fibrillation and many non-cardiac conditions and even strenuous exercise are&#xD;
      associated with elevated cTnT levels which are problematic to clinicians and may lead to&#xD;
      redundant use of diagnostic coronary angiography or &quot;overdiagnosis&quot; of ACS in the emergency&#xD;
      room workup.&#xD;
&#xD;
      The cardiac troponin (cTn) complex is part of the thin filaments of myocardium. Small part&#xD;
      (approximately 5% of total content) of troponins are cytosolic. These smaller cytosolic&#xD;
      fragments may more easily traverse across cell membranes that have become leaky for some&#xD;
      reason but not irreversibly damaged. Only cytoplasmic forms of troponin are contained in the&#xD;
      subcellular blebs which lyse upon early cTn release into the circulation. Bleb formation may&#xD;
      explain how troponin can appear in blood in the absence of cell necrosis. Still many aspects&#xD;
      of their intramyocardial degradation, their tissue release, and their degradation within and&#xD;
      elimination from the human circulation are still incompletely understood.&#xD;
&#xD;
      In the early hours of AMI, troponin is found in its full-size complex, but the complexed cTnT&#xD;
      degrades in a time-dependent pattern after the first hours. Small molecular weight troponin&#xD;
      fragments originating from the cytoplasm may traverse across leaky cell membranes not&#xD;
      completely damaged in various conditions without irreversible myocardial cell necrosis.&#xD;
&#xD;
      Commercial cTnT test detects all these fragments and may thus lead to false diagnosis of AMI.&#xD;
      At present, there is limited information based on small studies using complicated gel&#xD;
      filtration chromatography and Western blotting showing cTnT fragmentation in later phases of&#xD;
      AMI and in renal failure. These time-consuming analytical methods are, however, not suitable&#xD;
      for clinical purposes in the emergency room.&#xD;
&#xD;
      ANALYTICAL METHODS In this study we test a novel sensitive time-resolved immunofluorometric&#xD;
      assay, which has been developed at the biotechnology unit of the Department Biochemistry,&#xD;
      University of Turku, which enables us to measure cTnT from blood samples in its intact or&#xD;
      only slightly fragmented form. Thus, we can exclude the highly fragmented short forms of cTnT&#xD;
      from the analysis. This selectivity can be achieved with specific capture and tracer&#xD;
      antibodies that bind to carefully chosen epitopes located closer to the opposite ends of the&#xD;
      cTnT molecule. In the assay one of the antibodies is attached to a surface and acts as an&#xD;
      antigen capturing antibody. The capture-antigen pair can be detected with tracer antibody,&#xD;
      thus forming capture-antigen-tracer complex. In our case this tracer antibody has been&#xD;
      labeled with europium chelates which provide sensitive detection by time-resolved&#xD;
      fluorometry.&#xD;
&#xD;
      The aim of Tropo-Fragment study is to use the described preliminary assay format in the&#xD;
      clinical studies to evaluate:&#xD;
&#xD;
        -  TnT fragmentation and its time course in STEMI and NSTEMI&#xD;
&#xD;
        -  TnT fragmentation in renal failure, sepsis, strenuous exercise, stroke, atrial&#xD;
           fibrillation, takotsubo, myocarditis and healthy subjects&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 2, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2026</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2026</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <target_duration>1 Year</target_duration>
  <primary_outcome>
    <measure>The fragmentation rate of Troponin T</measure>
    <time_frame>Baseline</time_frame>
    <description>The proportion of fragmented Troponin T in patient cohort.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">1500</enrollment>
  <condition>Acute Myocardial Infarction Type 1</condition>
  <condition>Myocardial Injury</condition>
  <arm_group>
    <arm_group_label>Myocardial infarction</arm_group_label>
    <description>Recruited patients with STEMI or NSTEMI and elevated Troponin T</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Myocardial injury</arm_group_label>
    <description>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</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>troponin T fragmentation test</intervention_name>
    <description>laboratory test from blood sample</description>
    <arm_group_label>Myocardial infarction</arm_group_label>
    <arm_group_label>Myocardial injury</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Heparin plasma:&#xD;
&#xD;
        -  Troponin T control sample&#xD;
&#xD;
        -  Troponin T fragmentation sample&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients are prospectively recruited from the Heart Center, Department of Medicine and&#xD;
        Kidney Center of the study hospital. All patients aged 18 years are eligible.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Troponin T fragmentation sample collected from a recruited patient.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt;18&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Juhani K Airaksinen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Turku</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Juhani K Airaksinen, MD, PhD</last_name>
    <phone>+358 2 3131005</phone>
    <email>juhani.airaksinen@tyks.fi</email>
  </overall_contact>
  <location>
    <facility>
      <name>Turku University Hospital, Heart Center</name>
      <address>
        <city>Turku</city>
        <state>Varsinais-suomi</state>
        <zip>20521</zip>
        <country>Finland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Juhani KE Airaksinen, MD, PhD</last_name>
      <phone>+358 2 313 1079</phone>
      <email>juhani.airaksinen@tyks.fi</email>
    </contact>
    <contact_backup>
      <last_name>Samuli Jaakkola, MD, PhD</last_name>
      <phone>+358 2 3138 025</phone>
      <email>samuli.jaakkola@tyks.fi</email>
    </contact_backup>
    <investigator>
      <last_name>Juhani K Airaksinen, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Saara Wittfooth, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tapio Hellman, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Samuli Jaakkola, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kaj Metsärinne, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rami Aalto, MSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tuomas Paana, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kim Pettersson, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital Zurich</name>
      <address>
        <city>Zürich</city>
        <zip>8091 Zurich</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Enrolling by invitation</status>
  </location>
  <location_countries>
    <country>Finland</country>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>August 11, 2023</last_update_submitted>
  <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Turku</investigator_affiliation>
    <investigator_full_name>Juhani Airaksinen</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Troponin</keyword>
  <keyword>myocardial injury</keyword>
  <keyword>myocardial infarction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>Infarction</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04465591
org study id: T29/2020
nct id: NCT04465591
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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
observational model: Cohort
time perspective: Cross-Sectional
measure: The fragmentation rate of Troponin T
time frame: Baseline
description: The proportion of fragmented Troponin T in patient cohort.
arm group label: Myocardial infarction
description: Recruited patients with STEMI or NSTEMI and elevated Troponin T
arm group label: Myocardial injury
description: 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
intervention type: Diagnostic Test
intervention name: troponin T fragmentation test
description: laboratory test from blood sample
arm group label: Myocardial infarction
arm group label: Myocardial injury
Heparin plasma:

        -  Troponin T control sample

        -  Troponin T fragmentation sample
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Juhani K Airaksinen, MD, PhD
role: Principal Investigator
affiliation: University of Turku
last name: Juhani K Airaksinen, MD, PhD
phone: +358 2 3131005
email: juhani.airaksinen@tyks.fi
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
facility: 
status: Enrolling by invitation
country: Finland
country: Switzerland
responsible party type: Principal Investigator
investigator affiliation: University of Turku
investigator full name: Juhani Airaksinen
investigator title: Professor
mesh term: Myocardial Infarction
mesh term: Infarction
mesh term: Wounds and Injuries
sharing ipd: Undecided