<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/NCT03250728</url>
  </required_header>
  <id_info>
    <org_study_id>K170703J</org_study_id>
    <secondary_id>2017-A02141-52</secondary_id>
    <nct_id>NCT03250728</nct_id>
  </id_info>
  <brief_title>Role of the Endothelium in Stroke-like Episode Among CDG Patients</brief_title>
  <acronym>PECDG</acronym>
  <official_title>Role of the Endothelium in Stroke-like Episode Among CDG Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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 aim of the study is to evaluate the role of the endothelial barrier in the occurrence of&#xD;
      stroke-like episode. And to study the protein C system on the surface of the endothelium.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study consists in isolating endothelial progenitor cells in peripheral blood. After blood&#xD;
      puncture, PBMC (peripheral blood mononuclear cell) are isolated by Ficoll gradient and then&#xD;
      culturing in appropriated medium.&#xD;
&#xD;
      When cells are confluent, investigators can study the endothelial barrier by using&#xD;
      permeability assay and transendothelial resistance test (iCELLigence technology).&#xD;
&#xD;
      Then, protein C system will be studied. Indeed, EPCR (Endothelial protein C receptor) and TM&#xD;
      (thrombomodulin), are the two receptors responsible for the activation of protein C. The&#xD;
      expression of these receptors will be assessed in flow cytometry. The activated protein C is&#xD;
      able to interact with the third receptor PAR1 (Protease activated receptor 1) which is&#xD;
      responsible for the protective effects of the on the endothelial barrier. The PAR1 expression&#xD;
      will be studied in flow cytometry also.&#xD;
&#xD;
      In order to measure the capacity of the protein C system to generate activated protein C&#xD;
      investigators will assay an activated protein C generation on the cell surface.&#xD;
&#xD;
      All these assays will be realized in basal condition and in heat stress (42°C), to mimic the&#xD;
      stroke-like episode environment. Indeed, stroke-like episodes occur always during febrile&#xD;
      illness.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 23, 2017</start_date>
  <completion_date type="Actual">April 26, 2019</completion_date>
  <primary_completion_date type="Actual">April 26, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Endothelial permeability assay in basal condition</measure>
    <time_frame>at inclusion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Endothelial permeability assay after an heat shock</measure>
    <time_frame>at inclusion</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Activated protein C generation assay on the endothelial cell surface</measure>
    <time_frame>at inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantification of the endothelial receptors (EPCR, TM, PAR1)</measure>
    <time_frame>at inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endothelial permeability assay after an activated protein C incubation</measure>
    <time_frame>at inclusion</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Congenital Disorders of Glycosylation</condition>
  <arm_group>
    <arm_group_label>CDG with stroke-like history</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>CDG without stroke-like history</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Peripheral blood puncture</intervention_name>
    <description>Endothelial progenitor cells will be isolated from peripheral blood by density gradient and cultured in 10%FBS EGM2 medium&#xD;
On the EPCs we will study:&#xD;
the endothelial permeability&#xD;
the protein C system</description>
    <arm_group_label>CDG with stroke-like history</arm_group_label>
    <arm_group_label>CDG without stroke-like history</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients with CDG molecularly diagnosed&#xD;
&#xD;
          -  with stroke-like history or not&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  rejection to participate in research&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pascale De Lonlay, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Delphine Borgel, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hopital Necker enfants malades</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>January 7, 2020</last_update_submitted>
  <last_update_submitted_qc>January 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CDG</keyword>
  <keyword>Stroke-like</keyword>
  <keyword>Endothelial progenitor cells (EPCs)</keyword>
  <keyword>Protein C</keyword>
  <keyword>Congenital Disorders og Glycosylation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Congenital Disorders of Glycosylation</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/NCT03250728
org study id: K170703J
secondary id: 2017-A02141-52
nct id: NCT03250728
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of the study is to evaluate the role of the endothelial barrier in the occurrence of
      stroke-like episode. And to study the protein C system on the surface of the endothelium.
The study consists in isolating endothelial progenitor cells in peripheral blood. After blood
      puncture, PBMC (peripheral blood mononuclear cell) are isolated by Ficoll gradient and then
      culturing in appropriated medium.

      When cells are confluent, investigators can study the endothelial barrier by using
      permeability assay and transendothelial resistance test (iCELLigence technology).

      Then, protein C system will be studied. Indeed, EPCR (Endothelial protein C receptor) and TM
      (thrombomodulin), are the two receptors responsible for the activation of protein C. The
      expression of these receptors will be assessed in flow cytometry. The activated protein C is
      able to interact with the third receptor PAR1 (Protease activated receptor 1) which is
      responsible for the protective effects of the on the endothelial barrier. The PAR1 expression
      will be studied in flow cytometry also.

      In order to measure the capacity of the protein C system to generate activated protein C
      investigators will assay an activated protein C generation on the cell surface.

      All these assays will be realized in basal condition and in heat stress (42°C), to mimic the
      stroke-like episode environment. Indeed, stroke-like episodes occur always during febrile
      illness.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Endothelial permeability assay in basal condition
time frame: at inclusion
measure: Endothelial permeability assay after an heat shock
time frame: at inclusion
measure: Activated protein C generation assay on the endothelial cell surface
time frame: at inclusion
measure: Quantification of the endothelial receptors (EPCR, TM, PAR1)
time frame: at inclusion
measure: Endothelial permeability assay after an activated protein C incubation
time frame: at inclusion
arm group label: CDG with stroke-like history
arm group type: Other
arm group label: CDG without stroke-like history
arm group type: Other
intervention type: Biological
intervention name: Peripheral blood puncture
description: Endothelial progenitor cells will be isolated from peripheral blood by density gradient and cultured in 10%FBS EGM2 medium
On the EPCs we will study:
the endothelial permeability
the protein C system
arm group label: CDG with stroke-like history
arm group label: CDG without stroke-like history
criteria: 
gender: All
minimum age: 6 Years
maximum age: N/A
healthy volunteers: No
last name: Pascale De Lonlay, MD, PhD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Delphine Borgel, MD, PhD
role: Study Director
affiliation: Assistance Publique - Hôpitaux de Paris
facility: 
country: France
responsible party type: Sponsor
mesh term: Congenital Disorders of Glycosylation
sharing ipd: No