<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/NCT04423523</url>
  </required_header>
  <id_info>
    <org_study_id>RC19_0402</org_study_id>
    <nct_id>NCT04423523</nct_id>
  </id_info>
  <brief_title>Plasma Levels of Danger-Associated Molecular Patterns in Young Children After Cardiac Surgery Under Cardiopulmonary Bypass</brief_title>
  <acronym>IMMUNOPED2</acronym>
  <official_title>Plasma Levels of Danger-Associated Molecular Patterns (DAMPs) in Young Children After Cardiac Surgery Under Cardiopulmonary Bypass (IMMUNOPED 2)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nantes University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nantes 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>
      The investigators have previously reported that cardiac surgery with CPB ( cardiopulmonary&#xD;
      bypass) in young infants induced a drastic reduction in mHLA-DR ( Human Leucocyte Antigen)&#xD;
      expression, which represents one of innate immune mediator. Danger-Associated Molecular&#xD;
      Patterns (DAMPs) can elicit immune response and may subsequentely induce an immune-suppressed&#xD;
      state. The investigators hypothesize that CPB causes excessive DAMP release, leading to the&#xD;
      development of immune suppression. Thus, DAMPs release will be assessed in patients&#xD;
      undergoing CBP, and consequences on immune suppression will be evaluated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Plasma levels of heat shock protein (HSP 70), high mobility group box (HMGB1), S100A9 and&#xD;
      IL-33 will be measured at four time points (prior to the onset of CPB, Hour 6 postoperative,&#xD;
      day 1 and day 3 after surgery). HLA-DR gene expression will be determined before surgery and&#xD;
      at day 3 postoperative. The direct effect of DAMPs release and immune suppression will be&#xD;
      assessed by in vitro experiments.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 2, 2020</start_date>
  <completion_date type="Anticipated">April 2, 2024</completion_date>
  <primary_completion_date type="Actual">September 2, 2023</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>30 Days</target_duration>
  <primary_outcome>
    <measure>Plasma levels of heat shock protein (HSP 70), high mobility group box (HMGB1), S100A9 and IL-33 before and after CBP.</measure>
    <time_frame>prior to the onset of CPB, 6 hours, day 1 and day 3 after surgery</time_frame>
    <description>Change of plasma levels of DAMPs after cardiopulmonary bypass Plasma levels of heat shock protein (HSP 70), high mobility group box (HMGB1), S100A9 and IL-33 before and after CBP.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of DAMPs on immune function:In vitro change of HLA-DR expression.</measure>
    <time_frame>6 hours after surgery</time_frame>
    <description>In vitro change of HLA-DR expression induced by plasma containing different concentrations of DAMPs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of DAMPs on immune function:Secretion of IL-10 ( Interleukine 10).</measure>
    <time_frame>6 hours after surgery</time_frame>
    <description>Secretion of IL-10 by different immune cells induced by plasma containing different concentrations of DAMPs.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Cardiac Surgical Procedure</condition>
  <eligibility>
    <study_pop>
      <textblock>
        All patients admitted to pediatric resuscitation at the Nantes University Hospital after&#xD;
        cardiac surgery under CEC ( extra-corporal circulation) and aged less than 3 months meeting&#xD;
        the criteria for inclusion and non-inclusion of the study will be included. We can&#xD;
        objectify the recruitment of 80 patients in total over 2 years.&#xD;
&#xD;
        Since natural evolution (variation of rates and their kinetics) of the secretion of&#xD;
        different DAMPs during the first months of life is unknown, the investigators added a&#xD;
        control group to know the expression and kinetics of DAMPs outside cardiac surgery under&#xD;
        CEC. This control group will be defined by infants under 3 months of age undergoing heavy&#xD;
        digestive surgery and having a central venous catheter to facilitate access to blood&#xD;
        samples (n = 20).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients ≤ 3 months undergoing cardiac surgery with cardiopulmonary bypass&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lack of parental consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>3 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexis Chenouard</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nantes University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Alexis Chenouard, ph</last_name>
    <phone>02.44.76.82.21</phone>
    <email>alexis.chenouard@chu-nantes.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Anne Chauvire-Drouard</last_name>
    <phone>02.40.08.78.05</phone>
    <email>anne.drouard@chu-nantes.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Nantes University Hospital</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alexis Chenouard, ph</last_name>
      <phone>02.44.76.82.21</phone>
      <email>alexis.chenouard@chu-nantes.fr</email>
    </contact>
    <contact_backup>
      <last_name>Anne chauviré-Drouard</last_name>
      <phone>02.40.08.78.05</phone>
      <email>anne.drouard@chu-nantes.fr</email>
    </contact_backup>
    <investigator>
      <last_name>Alexis Chenouard, PH</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>May 14, 2020</study_first_submitted>
  <study_first_submitted_qc>June 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>September 6, 2023</last_update_submitted>
  <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cardiopulmonary bypass; immunosuppression; infant</keyword>
  <keyword>immunosuppression</keyword>
  <keyword>infant</keyword>
  <!-- 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/NCT04423523
org study id: RC19_0402
nct id: NCT04423523
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The investigators have previously reported that cardiac surgery with CPB ( cardiopulmonary
      bypass) in young infants induced a drastic reduction in mHLA-DR ( Human Leucocyte Antigen)
      expression, which represents one of innate immune mediator. Danger-Associated Molecular
      Patterns (DAMPs) can elicit immune response and may subsequentely induce an immune-suppressed
      state. The investigators hypothesize that CPB causes excessive DAMP release, leading to the
      development of immune suppression. Thus, DAMPs release will be assessed in patients
      undergoing CBP, and consequences on immune suppression will be evaluated.
Plasma levels of heat shock protein (HSP 70), high mobility group box (HMGB1), S100A9 and
      IL-33 will be measured at four time points (prior to the onset of CPB, Hour 6 postoperative,
      day 1 and day 3 after surgery). HLA-DR gene expression will be determined before surgery and
      at day 3 postoperative. The direct effect of DAMPs release and immune suppression will be
      assessed by in vitro experiments.
observational model: Case-Control
time perspective: Prospective
measure: Plasma levels of heat shock protein (HSP 70), high mobility group box (HMGB1), S100A9 and IL-33 before and after CBP.
time frame: prior to the onset of CPB, 6 hours, day 1 and day 3 after surgery
description: Change of plasma levels of DAMPs after cardiopulmonary bypass Plasma levels of heat shock protein (HSP 70), high mobility group box (HMGB1), S100A9 and IL-33 before and after CBP.
measure: Effect of DAMPs on immune function:In vitro change of HLA-DR expression.
time frame: 6 hours after surgery
description: In vitro change of HLA-DR expression induced by plasma containing different concentrations of DAMPs.
measure: Effect of DAMPs on immune function:Secretion of IL-10 ( Interleukine 10).
time frame: 6 hours after surgery
description: Secretion of IL-10 by different immune cells induced by plasma containing different concentrations of DAMPs.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 3 Months
healthy volunteers: No
last name: Alexis Chenouard
role: Principal Investigator
affiliation: Nantes University Hospital
last name: Alexis Chenouard, ph
phone: 02.44.76.82.21
email: alexis.chenouard@chu-nantes.fr
last name: Anne Chauvire-Drouard
phone: 02.40.08.78.05
email: anne.drouard@chu-nantes.fr
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: France
responsible party type: Sponsor