<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/NCT04435457</url>
  </required_header>
  <id_info>
    <org_study_id>STU-2020-0359</org_study_id>
    <nct_id>NCT04435457</nct_id>
  </id_info>
  <brief_title>Cardiovascular Implications of COVID-19</brief_title>
  <official_title>Uncovering the Cardiac Phenotype of Individuals With SARS-COV-2 and Cardiac Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      At the end of December of 2019, a series of patients in Wuhan, China were struck with a&#xD;
      mysterious respiratory infection. These isolated events have rapidly grown into a deadly,&#xD;
      global pandemic. This pandemic is caused by the Severe Acute Respiratory Syndrome Coronavirus&#xD;
      2 (SARS-CoV-2), which results in the Coronavirus Disease 2019 (COVID-19). For individuals&#xD;
      infected with COVID-19, approximately 30% of the hospitalized cases are associated with&#xD;
      cardiovascular complications. Data are emerging that individuals with pre-exiting conditions&#xD;
      (like hypertension, diabetes, cancer, or medical issues related to the immune system) are&#xD;
      most susceptible to complications related to COVID-19. Furthermore, individuals of certain&#xD;
      racial and ethnic backgrounds (e.g. African American and Hispanic) are at a higher risk of&#xD;
      death from COVID-19. Despite these emerging observations, it remains unclear who will develop&#xD;
      the cardiovascular complications (acute myocardial injury with evidence of a myocarditis-like&#xD;
      picture and cardiogenic shock) and what the long term sequelae of this disease will be for&#xD;
      survivors of this infection after hospitalization. Thus, the goals of this project are to&#xD;
      better understand the epidemiology of cardiac injury in acutely ill COVID-19 patients through&#xD;
      deep cardiac phenotyping and identify the molecular profile of individuals most susceptible&#xD;
      to cardiac injury from COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a cross-sectional cohort study of participants who will undergo a detailed&#xD;
      cardiovascular imaging evaluation and blood draw once they have recuperated from a prior&#xD;
      index-hospitalization at Clements University Hospital or Parkland Memorial Hospital in&#xD;
      Dallas, Texas, USA for COVID-19 and are no longer contagious (~4-6 weeks post&#xD;
      hospitalization). Due to the uncertainty with which the extent of cardiac injury represents&#xD;
      phenotypic cardiac manifestations in COVID-19, the investigators plan to enroll individuals&#xD;
      according to their highest, in-hospital, (high sensitivity - cardiac troponin T) hs-cTnT. The&#xD;
      following proposed stratification scheme will afford testing a spectrum hs-cTnT levels.&#xD;
&#xD;
      Table: Enrollment strata by hs-cTnT (N=70)&#xD;
&#xD;
      hs-cTnT [ng/L] &lt; 50 50-100 101-500 &gt; 500&#xD;
&#xD;
      Enrollment N=20 N=20 N=20 N=10&#xD;
&#xD;
      The investigators propose the following exploratory protocol for deep phenotyping to&#xD;
      characterize surviving patients with COVID-19 and elevated hs-cTnT during hospitalization.&#xD;
&#xD;
      All participants will undergo a protocolized multiparametric cardiac magnetic resonance&#xD;
      imaging (CMR) assessment with an electrocardiography-gated breath hold protocol under the&#xD;
      oversight of study personnel and read by a reader blinded to hs-cTnT data from the COVID-19&#xD;
      index hospitalization. Conventional 1H CMR evaluations will include T2 maps, native and&#xD;
      post-contrast T1 maps, as well as extracellular volume index calculation and late gadolinium&#xD;
      for inflammatory injury. Standardized adenosine hyperemic stress perfusion CMR will be&#xD;
      performed for quantitative myocardial blood flow analysis. In addition to conventional 1H CMR&#xD;
      a subset of 5 patients from the highest and lowest troponin groups, age- and BMI-matched,&#xD;
      will undergo hyperpolarized 13C metabolic CMR with infusion of [1-13C] pyruvate under fasting&#xD;
      conditions to assess inflammation and post carbohydrate load to assess a decrease in&#xD;
      myocardial mitochondrial oxidative metabolism.&#xD;
&#xD;
      Biospecimens will be collected by study personnel at the time of CMR or preliminary study&#xD;
      site visit. A fasting venous blood sample (50 cc) will be collected, maintained on ice and&#xD;
      transported to the Mammen Laboratory, which is located on the campus of UT Southwestern. Both&#xD;
      serum and plasma will be isolated and aliquoted for storage and immediately frozen and stored&#xD;
      until use and will not undergo any freeze-thaw cycles. RNA and protein will be extracted from&#xD;
      the samples for biomarker and autoantibody (AAb) assays. The presence of cardiac-specific&#xD;
      AAbs has been shown to be involved in both the manifestation and development of cardiac&#xD;
      disease manifestation and predicting disease development. Utilizing a customized ELISA-based&#xD;
      detection assay, ~20 circulating cardiac-specific AAbs that have been reported to be&#xD;
      associated with heart failure will be assessed and quantified during the early (1-2 months&#xD;
      post-hospitalization) phases of the patient post COVID-19 hospitalization course.&#xD;
&#xD;
      Leukocytes will be isolated from the biospecimens samples and genomic DNA will be extracted&#xD;
      from the cells to perform Next Generation Whole Exome Sequencing (WES). These studies will be&#xD;
      undertaken in the Next-Generation Sequencing Core on campus. Capitalizing on a&#xD;
      well-established research collaboration between the Mammen Laboratory and the McDermott&#xD;
      bioinformatics group, the WES data will be analyzed for genetic mutations associated with&#xD;
      cardiomyopathy as well as autoimmunity.&#xD;
&#xD;
      If funds are available, both the imaging and molecular assessments will be duplicated in&#xD;
      individuals with paired data after an additional 10-12 months from hospitalization.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    COVID-19 natural history has changed and no further patients meet eligibility as&#xD;
    hospitalizations are at a minimum.&#xD;
  </why_stopped>
  <start_date type="Actual">September 1, 2020</start_date>
  <completion_date type="Actual">May 20, 2023</completion_date>
  <primary_completion_date type="Actual">May 20, 2023</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>Prevalence of Myocarditis</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>Patterns of late gadolinium enhancement and T1 and T2 mapping consistent with myocarditis on a post-hospitalization cardiac magnetic resonance imaging examination</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prevalence of cardiac abnormalities by cardiac magnetic resonance imaging</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>This includes categorically abnormal structural, mechanical functional, vascular, and metabolic using cardiac magnetic resonance imaging</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of molecular and genetic immune system abnormalities</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>Presence of cardiac autoantibodies and defects within the immune system as detected by Whole Exome Sequencing making an individual susceptible to subacute cardiac injury during COVID-19 infection</description>
  </secondary_outcome>
  <enrollment type="Actual">42</enrollment>
  <condition>SARS-CoV 2</condition>
  <condition>SARS Pneumonia</condition>
  <condition>COVID-19</condition>
  <condition>SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere</condition>
  <condition>Cardiac Complication</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      A fasting venous blood sample (50 cc) will be collected, maintained on ice and transported to&#xD;
      the Mammen Laboratory, which is located on the campus of UT Southwestern. Both serum and&#xD;
      plasma will be isolated and aliquoted for storage and immediately frozen and stored until use&#xD;
      and will not undergo any freeze-thaw cycles&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Consenting adults with a prior hospitalization for COVID-19 at either Parkland Memorial&#xD;
        Hospital or Clements University Hospital in Dallas, Texas, USA who have recovered and are&#xD;
        no-longer at-risk of COVID-19 disease transmission according the United States Centers for&#xD;
        Disease Control guidelines will be considered for inclusion.&#xD;
&#xD;
        All patients admitted to either hospital with suspected or confirmed COVID-19 receive an&#xD;
        in-hospital standard-of-care metabolic, cardiac, and inflammatory biomarker protocolized&#xD;
        assessment that includes daily basic metabolic panels, complete blood counts with&#xD;
        differential, hs-cTnT, and C-reactive protein (CRP) coupled with every third day amino&#xD;
        terminal pro-B-type natriuretic peptide (NT-proBNP), D-dimer, and ferritin. These labs are&#xD;
        obtained from the day of admission to discharge. ]&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and non-pregnant women 18-80 years old who were previously hospitalized with&#xD;
             confirmed COVID-19&#xD;
&#xD;
          -  Were alive at the time of discharge from COVID-19 hospitalization&#xD;
&#xD;
          -  Had measured hs-cTnT levels during hospitalization&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior cardiovascular disease (before COVID-19 infection), defined as self-reported&#xD;
             history or electronic medical record diagnosis of cardiac arrest, myocardial&#xD;
             infarction, coronary revascularization, heart failure, or stroke prior to COVID-19&#xD;
             hospitalization&#xD;
&#xD;
          -  Urgent-coronary revascularization or type I myocardial infarction within the preceding&#xD;
             30 days&#xD;
&#xD;
          -  Cardiac transplantation&#xD;
&#xD;
          -  Body weight &gt;250 lbs&#xD;
&#xD;
          -  Moderate to severe chronic renal dysfunction defined by an eGFR ≤30 mL/min/1.73 m2&#xD;
&#xD;
          -  Inability to safely undergo a CMR&#xD;
&#xD;
          -  Unwilling or unable to provide informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Justin L Grodin, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>UT Southwestern Medical Center at Dallas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>May 20, 2023</last_update_submitted>
  <last_update_submitted_qc>May 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
    <investigator_full_name>Justin Grodin</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>SARS-CoV 2</keyword>
  <keyword>Troponin</keyword>
  <keyword>Cardiac injury</keyword>
  <keyword>COVID-19</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Severe Acute Respiratory Syndrome</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/NCT04435457
org study id: STU-2020-0359
nct id: NCT04435457
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
At the end of December of 2019, a series of patients in Wuhan, China were struck with a
      mysterious respiratory infection. These isolated events have rapidly grown into a deadly,
      global pandemic. This pandemic is caused by the Severe Acute Respiratory Syndrome Coronavirus
      2 (SARS-CoV-2), which results in the Coronavirus Disease 2019 (COVID-19). For individuals
      infected with COVID-19, approximately 30% of the hospitalized cases are associated with
      cardiovascular complications. Data are emerging that individuals with pre-exiting conditions
      (like hypertension, diabetes, cancer, or medical issues related to the immune system) are
      most susceptible to complications related to COVID-19. Furthermore, individuals of certain
      racial and ethnic backgrounds (e.g. African American and Hispanic) are at a higher risk of
      death from COVID-19. Despite these emerging observations, it remains unclear who will develop
      the cardiovascular complications (acute myocardial injury with evidence of a myocarditis-like
      picture and cardiogenic shock) and what the long term sequelae of this disease will be for
      survivors of this infection after hospitalization. Thus, the goals of this project are to
      better understand the epidemiology of cardiac injury in acutely ill COVID-19 patients through
      deep cardiac phenotyping and identify the molecular profile of individuals most susceptible
      to cardiac injury from COVID-19.
This will be a cross-sectional cohort study of participants who will undergo a detailed
      cardiovascular imaging evaluation and blood draw once they have recuperated from a prior
      index-hospitalization at Clements University Hospital or Parkland Memorial Hospital in
      Dallas, Texas, USA for COVID-19 and are no longer contagious (~4-6 weeks post
      hospitalization). Due to the uncertainty with which the extent of cardiac injury represents
      phenotypic cardiac manifestations in COVID-19, the investigators plan to enroll individuals
      according to their highest, in-hospital, (high sensitivity - cardiac troponin T) hs-cTnT. The
      following proposed stratification scheme will afford testing a spectrum hs-cTnT levels.

      Table: Enrollment strata by hs-cTnT (N=70)

      hs-cTnT [ng/L] < 50 50-100 101-500 > 500

      Enrollment N=20 N=20 N=20 N=10

      The investigators propose the following exploratory protocol for deep phenotyping to
      characterize surviving patients with COVID-19 and elevated hs-cTnT during hospitalization.

      All participants will undergo a protocolized multiparametric cardiac magnetic resonance
      imaging (CMR) assessment with an electrocardiography-gated breath hold protocol under the
      oversight of study personnel and read by a reader blinded to hs-cTnT data from the COVID-19
      index hospitalization. Conventional 1H CMR evaluations will include T2 maps, native and
      post-contrast T1 maps, as well as extracellular volume index calculation and late gadolinium
      for inflammatory injury. Standardized adenosine hyperemic stress perfusion CMR will be
      performed for quantitative myocardial blood flow analysis. In addition to conventional 1H CMR
      a subset of 5 patients from the highest and lowest troponin groups, age- and BMI-matched,
      will undergo hyperpolarized 13C metabolic CMR with infusion of [1-13C] pyruvate under fasting
      conditions to assess inflammation and post carbohydrate load to assess a decrease in
      myocardial mitochondrial oxidative metabolism.

      Biospecimens will be collected by study personnel at the time of CMR or preliminary study
      site visit. A fasting venous blood sample (50 cc) will be collected, maintained on ice and
      transported to the Mammen Laboratory, which is located on the campus of UT Southwestern. Both
      serum and plasma will be isolated and aliquoted for storage and immediately frozen and stored
      until use and will not undergo any freeze-thaw cycles. RNA and protein will be extracted from
      the samples for biomarker and autoantibody (AAb) assays. The presence of cardiac-specific
      AAbs has been shown to be involved in both the manifestation and development of cardiac
      disease manifestation and predicting disease development. Utilizing a customized ELISA-based
      detection assay, ~20 circulating cardiac-specific AAbs that have been reported to be
      associated with heart failure will be assessed and quantified during the early (1-2 months
      post-hospitalization) phases of the patient post COVID-19 hospitalization course.

      Leukocytes will be isolated from the biospecimens samples and genomic DNA will be extracted
      from the cells to perform Next Generation Whole Exome Sequencing (WES). These studies will be
      undertaken in the Next-Generation Sequencing Core on campus. Capitalizing on a
      well-established research collaboration between the Mammen Laboratory and the McDermott
      bioinformatics group, the WES data will be analyzed for genetic mutations associated with
      cardiomyopathy as well as autoimmunity.

      If funds are available, both the imaging and molecular assessments will be duplicated in
      individuals with paired data after an additional 10-12 months from hospitalization.
observational model: Cohort
time perspective: Cross-Sectional
measure: Prevalence of Myocarditis
time frame: Up to 4 weeks
description: Patterns of late gadolinium enhancement and T1 and T2 mapping consistent with myocarditis on a post-hospitalization cardiac magnetic resonance imaging examination
measure: Prevalence of cardiac abnormalities by cardiac magnetic resonance imaging
time frame: Up to 4 weeks
description: This includes categorically abnormal structural, mechanical functional, vascular, and metabolic using cardiac magnetic resonance imaging
measure: Prevalence of molecular and genetic immune system abnormalities
time frame: Up to 4 weeks
description: Presence of cardiac autoantibodies and defects within the immune system as detected by Whole Exome Sequencing making an individual susceptible to subacute cardiac injury during COVID-19 infection
A fasting venous blood sample (50 cc) will be collected, maintained on ice and transported to
      the Mammen Laboratory, which is located on the campus of UT Southwestern. Both serum and
      plasma will be isolated and aliquoted for storage and immediately frozen and stored until use
      and will not undergo any freeze-thaw cycles
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Justin L Grodin, MD, MPH
role: Principal Investigator
affiliation: UT Southwestern Medical Center at Dallas
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Texas Southwestern Medical Center
investigator full name: Justin Grodin
investigator title: Assistant Professor
mesh term: COVID-19
mesh term: Severe Acute Respiratory Syndrome
sharing ipd: Undecided