<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/NCT03749551</url>
  </required_header>
  <id_info>
    <org_study_id>TrueTypeCKD 4/17</org_study_id>
    <nct_id>NCT03749551</nct_id>
  </id_info>
  <brief_title>Towards Understanding the Phenotype of Cardiovascular Disease in CKD - TRUE-Type-CKD Study</brief_title>
  <acronym>TRUE-TypeCKD</acronym>
  <official_title>TowaRds Understanding the phEnoTYPEs of Cardiovascular Dysfunction in Patients With Chronic Kidney Disease and HaemoDialysis Using Cardiovascular Magnetic Resonance Imaging - TRUE-Type-CKD Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johann Wolfgang Goethe University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kerckhoff Klinik</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Johann Wolfgang Goethe University Hospital</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>
      Premature cardiovascular disease (CVD) is the leading cause of death in patients with kidney&#xD;
      disease (CKD). Excessive cardiac mortality is thought to be secondary to non-atherosclerotic&#xD;
      processes, with left ventricular (LV) hypertrophy (LVH) and remodelling being the predominant&#xD;
      phenotypical features. Along with other risk factors, subclinical ischaemia and haemodynamic&#xD;
      perturbations associated with haemodialysis (HD) are thought to contribute to the ultimate&#xD;
      development of LV systolic and diastolic dysfunction. The development of these adverse&#xD;
      features reflects a specific cardiomyopathy due to CKD and subsequently, to uraemia. Patients&#xD;
      receiving hemodialysis (HD) have a higher incidence rate of heart failure (predominantly with&#xD;
      preserved ejection fraction), with phenotypically eccentric hypertrophic remodelling,&#xD;
      systolic and diastolic dysfunction as well as high rate of interstitial myocardial fibrosis.&#xD;
      Detection and ultimately reversal of the development of this CKD-related cardiomyopathy are&#xD;
      important goals for improving the CVD, morbidity and mortality of CKD patients.The objectives&#xD;
      of this study are, firstly, to investigate the complex myocardial phenotype in patients with&#xD;
      various stages of CKD, secondly, to relate the CMR-measures to outcome, and thirdly, to be&#xD;
      able to estimate the effects of chronic uremia/hypervolemia. Deciphering the predominant&#xD;
      driver of remodelling on an individual level may help to personalise anti-remodelling&#xD;
      strategies. Native T1 and T2 mapping imaging provide non-invasive imaging tools to detect&#xD;
      myocardial fibrosis and oedema, respectively. Prognostic associations of these measures may&#xD;
      clarify the relative prevalence of adverse phenotype and their relative contribution to&#xD;
      adverse events and poor outcome. The role of chronic water retention and uraemia may be&#xD;
      associated with interstitial myocardial oedema promoting further the remodelling process.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 28, 2018</start_date>
  <completion_date type="Actual">June 14, 2021</completion_date>
  <primary_completion_date type="Actual">June 14, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>survival</measure>
    <time_frame>1 year</time_frame>
    <description>number of deaths</description>
  </primary_outcome>
  <primary_outcome>
    <measure>survival</measure>
    <time_frame>5 year</time_frame>
    <description>number of deaths</description>
  </primary_outcome>
  <primary_outcome>
    <measure>rate of death due to cardiovascular causes</measure>
    <time_frame>1 year</time_frame>
    <description>number of participants died due to death due to myocardial infarction, sudden cardiac death, heart failure</description>
  </primary_outcome>
  <primary_outcome>
    <measure>rate of death due to cardiovascular causes</measure>
    <time_frame>5 year</time_frame>
    <description>number of participants died due to death due to myocardial infarction, sudden cardiac death, heart failure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>rate of heart failure events</measure>
    <time_frame>1 year</time_frame>
    <description>number of participants with heart failure death and hospitalisation due to heart failure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rate of heart failure events</measure>
    <time_frame>5 year</time_frame>
    <description>number of participants with heart failure death and hospitalisation due to heart failure</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in native T1 and T2 (in msec) pre and post haemodialysis</measure>
    <time_frame>24 hour</time_frame>
    <description>measurement of change in magnetisation relaxation (in msec)</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">276</enrollment>
  <condition>Heart Failure</condition>
  <condition>Cardiomyopathies</condition>
  <condition>Chronic Kidney Diseases</condition>
  <condition>Hypertrophy, Left Ventricular</condition>
  <arm_group>
    <arm_group_label>Participants</arm_group_label>
    <description>diagnostic test - patients serving as their own controls</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>cardiac magnetic resonance (CMR) post haemodialysis</intervention_name>
    <description>patients will undergo a second CMR scan immediately after receiving haemodialysis (native CMR study)</description>
    <arm_group_label>Participants</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        patients with established diagnosis of chronic kidney disease&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adults &gt;18 years of age&#xD;
&#xD;
          2. Able to provide informed consent&#xD;
&#xD;
          3. Chronic kidney disease stages G3-5 (eGFR&lt;59 ml/min/1.73m2)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Absence of absolute clinical indication for MRI studies (MR unsafe or incompatible&#xD;
             devices, aneurysm clips, cochlear implants, loose metal foreign objects)&#xD;
&#xD;
          2. Absolute contraindications to gadolinium contrast agent (previous allergic reaction or&#xD;
             pregnancy),&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University Hospital Frankfurt</name>
      <address>
        <city>Frankfurt</city>
        <state>Hessen</state>
        <zip>Frankfurt am Main</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <results_reference>
    <citation>Arcari L, Engel J, Freiwald T, Zhou H, Zainal H, Gawor M, Buettner S, Geiger H, Hauser I, Nagel E, Puntmann VO. Cardiac biomarkers in chronic kidney disease are independently associated with myocardial edema and diffuse fibrosis by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2021 Jun 7;23(1):71. doi: 10.1186/s12968-021-00762-z.</citation>
    <PMID>34092229</PMID>
  </results_reference>
  <results_reference>
    <citation>Valbuena-Lopez SC, Camastra G, Cacciotti L, Nagel E, Puntmann VO, Arcari L. Cardiac Imaging Biomarkers in Chronic Kidney Disease. Biomolecules. 2023 Apr 29;13(5):773. doi: 10.3390/biom13050773.</citation>
    <PMID>37238643</PMID>
  </results_reference>
  <results_reference>
    <citation>Chen M, Arcari L, Engel J, Freiwald T, Platschek S, Zhou H, Zainal H, Buettner S, Zeiher AM, Geiger H, Hauser I, Nagel E, Puntmann VO. Aortic stiffness is independently associated with interstitial myocardial fibrosis by native T1 and accelerated in the presence of chronic kidney disease. Int J Cardiol Heart Vasc. 2019 Jun 26;24:100389. doi: 10.1016/j.ijcha.2019.100389. eCollection 2019 Sep.</citation>
    <PMID>31304234</PMID>
  </results_reference>
  <results_reference>
    <citation>Arcari L, Hinojar R, Engel J, Freiwald T, Platschek S, Zainal H, Zhou H, Vasquez M, Keller T, Rolf A, Geiger H, Hauser I, Vogl TJ, Zeiher AM, Volpe M, Nagel E, Puntmann VO. Native T1 and T2 provide distinctive signatures in hypertrophic cardiac conditions - Comparison of uremic, hypertensive and hypertrophic cardiomyopathy. Int J Cardiol. 2020 May 1;306:102-108. doi: 10.1016/j.ijcard.2020.03.002. Epub 2020 Mar 3.</citation>
    <PMID>32169347</PMID>
  </results_reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>November 17, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>July 12, 2023</last_update_submitted>
  <last_update_submitted_qc>July 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Johann Wolfgang Goethe University Hospital</investigator_affiliation>
    <investigator_full_name>Valentina Puentmann</investigator_full_name>
    <investigator_title>Principal Investigator, Clinical professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Hypertrophy, Left Ventricular</mesh_term>
    <mesh_term>Hypertrophy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03749551
org study id: TrueTypeCKD 4/17
nct id: NCT03749551
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Premature cardiovascular disease (CVD) is the leading cause of death in patients with kidney
      disease (CKD). Excessive cardiac mortality is thought to be secondary to non-atherosclerotic
      processes, with left ventricular (LV) hypertrophy (LVH) and remodelling being the predominant
      phenotypical features. Along with other risk factors, subclinical ischaemia and haemodynamic
      perturbations associated with haemodialysis (HD) are thought to contribute to the ultimate
      development of LV systolic and diastolic dysfunction. The development of these adverse
      features reflects a specific cardiomyopathy due to CKD and subsequently, to uraemia. Patients
      receiving hemodialysis (HD) have a higher incidence rate of heart failure (predominantly with
      preserved ejection fraction), with phenotypically eccentric hypertrophic remodelling,
      systolic and diastolic dysfunction as well as high rate of interstitial myocardial fibrosis.
      Detection and ultimately reversal of the development of this CKD-related cardiomyopathy are
      important goals for improving the CVD, morbidity and mortality of CKD patients.The objectives
      of this study are, firstly, to investigate the complex myocardial phenotype in patients with
      various stages of CKD, secondly, to relate the CMR-measures to outcome, and thirdly, to be
      able to estimate the effects of chronic uremia/hypervolemia. Deciphering the predominant
      driver of remodelling on an individual level may help to personalise anti-remodelling
      strategies. Native T1 and T2 mapping imaging provide non-invasive imaging tools to detect
      myocardial fibrosis and oedema, respectively. Prognostic associations of these measures may
      clarify the relative prevalence of adverse phenotype and their relative contribution to
      adverse events and poor outcome. The role of chronic water retention and uraemia may be
      associated with interstitial myocardial oedema promoting further the remodelling process.
observational model: Cohort
time perspective: Prospective
measure: survival
time frame: 1 year
description: number of deaths
measure: survival
time frame: 5 year
description: number of deaths
measure: rate of death due to cardiovascular causes
time frame: 1 year
description: number of participants died due to death due to myocardial infarction, sudden cardiac death, heart failure
measure: rate of death due to cardiovascular causes
time frame: 5 year
description: number of participants died due to death due to myocardial infarction, sudden cardiac death, heart failure
measure: rate of heart failure events
time frame: 1 year
description: number of participants with heart failure death and hospitalisation due to heart failure
measure: rate of heart failure events
time frame: 5 year
description: number of participants with heart failure death and hospitalisation due to heart failure
measure: Change in native T1 and T2 (in msec) pre and post haemodialysis
time frame: 24 hour
description: measurement of change in magnetisation relaxation (in msec)
arm group label: Participants
description: diagnostic test - patients serving as their own controls
intervention type: Diagnostic Test
intervention name: cardiac magnetic resonance (CMR) post haemodialysis
description: patients will undergo a second CMR scan immediately after receiving haemodialysis (native CMR study)
arm group label: Participants
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Germany
citation: Arcari L, Engel J, Freiwald T, Zhou H, Zainal H, Gawor M, Buettner S, Geiger H, Hauser I, Nagel E, Puntmann VO. Cardiac biomarkers in chronic kidney disease are independently associated with myocardial edema and diffuse fibrosis by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2021 Jun 7;23(1):71. doi: 10.1186/s12968-021-00762-z.
PMID: 34092229
citation: Valbuena-Lopez SC, Camastra G, Cacciotti L, Nagel E, Puntmann VO, Arcari L. Cardiac Imaging Biomarkers in Chronic Kidney Disease. Biomolecules. 2023 Apr 29;13(5):773. doi: 10.3390/biom13050773.
PMID: 37238643
citation: Chen M, Arcari L, Engel J, Freiwald T, Platschek S, Zhou H, Zainal H, Buettner S, Zeiher AM, Geiger H, Hauser I, Nagel E, Puntmann VO. Aortic stiffness is independently associated with interstitial myocardial fibrosis by native T1 and accelerated in the presence of chronic kidney disease. Int J Cardiol Heart Vasc. 2019 Jun 26;24:100389. doi: 10.1016/j.ijcha.2019.100389. eCollection 2019 Sep.
PMID: 31304234
citation: Arcari L, Hinojar R, Engel J, Freiwald T, Platschek S, Zainal H, Zhou H, Vasquez M, Keller T, Rolf A, Geiger H, Hauser I, Vogl TJ, Zeiher AM, Volpe M, Nagel E, Puntmann VO. Native T1 and T2 provide distinctive signatures in hypertrophic cardiac conditions - Comparison of uremic, hypertensive and hypertrophic cardiomyopathy. Int J Cardiol. 2020 May 1;306:102-108. doi: 10.1016/j.ijcard.2020.03.002. Epub 2020 Mar 3.
PMID: 32169347
responsible party type: Principal Investigator
investigator affiliation: Johann Wolfgang Goethe University Hospital
investigator full name: Valentina Puentmann
investigator title: Principal Investigator, Clinical professor
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Cardiomyopathies
mesh term: Hypertrophy, Left Ventricular
mesh term: Hypertrophy
sharing ipd: No