<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/NCT03816189</url>
  </required_header>
  <id_info>
    <org_study_id>2017_10</org_study_id>
    <secondary_id>2017-A02587-46</secondary_id>
    <nct_id>NCT03816189</nct_id>
  </id_info>
  <brief_title>Role of Eosinophil in Fibrogenesis of Systemic Sclerosis</brief_title>
  <acronym>EOFIB-SSC</acronym>
  <official_title>Role of Blood and Tissue Eosinophils in the Fibrogenesis of Systemic Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Lille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Lille</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>
      Eosinophils are involved in tissue remodeling and fibrosis in many inflammatory diseases.&#xD;
      Systemic sclerosis (SSc) is an autoimmune disease with fibrotic skin and lung complications.&#xD;
      The profibrosing properties and data from the SSc literature suggest a possible role of the&#xD;
      eosinophils in the process of fibrogenesis of SSc.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      it will assess the activation state of blood eosinophils in SSc patients compared to healthy&#xD;
      controls (ECP production in vitro, surface activation markers, whole transcriptome array,&#xD;
      ..).&#xD;
&#xD;
      it will also study skin eosinophils and their recruitment (extracellular eosinophil granules,&#xD;
      eotaxins production in skin, ..)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">October 3, 2018</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <study_type>Observational</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>
  <primary_outcome>
    <measure>Comparison of ECP concentrations in supernatants of eosinophils culture</measure>
    <time_frame>Baseline: one session</time_frame>
    <description>Eosinophils will be sorted, stimulated in vitro for 2 hours and ECP concentration will be assessed in supernatants</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of median fluorescence intensities of several surface markers on blood eosinophils, or comparison of percentages of positive cells among all eosinophils for a given marker (flow cytometry)</measure>
    <time_frame>Baseline: one session</time_frame>
    <description>MFI/% of CD69, HLA class II, CD9, CD11c, CD44, CCR3, CRTH2, IL-5R on blood eosinophils</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene expression profiles will be compared between SSc patients and healthy controls (whole transcriptome assay)</measure>
    <time_frame>Baseline: one session</time_frame>
    <description>Whole genome, transcriptomic approach (differentially expressed genes will be identified using a fold change cutoff)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In skin biopsies: density of eosinophils, extracellular ECP and MBP deposits (absent in healthy skin), and density of eotaxin-1-producing cells will be assessed in damaged skin and apparently healthy skin of SSc patients</measure>
    <time_frame>Baseline: one session</time_frame>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">65</enrollment>
  <condition>Systemic Sclerosis</condition>
  <condition>Systemic Scleroderma</condition>
  <arm_group>
    <arm_group_label>Diffuse SSc</arm_group_label>
    <description>Recruitment of 20 patients with diffuse SSc</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Limited SSc</arm_group_label>
    <description>Recruitment of 20 patients with limited SSc</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy subjects</arm_group_label>
    <description>Recruitment of 20 healthy subjects (control)</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Blood test</intervention_name>
    <description>Patients in each group will have a blood sample (9x7 mL) for eosinophils isolation, study of activation markers on whole blood and serum biomarkers testing</description>
    <arm_group_label>Diffuse SSc</arm_group_label>
    <arm_group_label>Healthy subjects</arm_group_label>
    <arm_group_label>Limited SSc</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Skin biopsies</intervention_name>
    <description>In patients who will accept, skin biopsies will be performed in damaged and apparently normal skin, excluding fingers, hands, feet and face (biopsies are facultative)</description>
    <arm_group_label>Diffuse SSc</arm_group_label>
    <arm_group_label>Limited SSc</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood, Eosinophils, tissue&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The active line of the Internal Medicine department (&gt; 400 sclerodermic patients)&#xD;
        guarantees the recruitment of 20 diffuse forms and 20 limited forms&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  For SSc patients:&#xD;
&#xD;
          -  Meeting the 2013 ACR-EULAR criteria for diffuse SSc (n = 20) and limited SSc (n = 20)&#xD;
&#xD;
          -  Having signed the informed consent&#xD;
&#xD;
          -  Eosinophils ≥ 0.1 G / L on the last blood test (&lt;3 months)&#xD;
&#xD;
        For healthy subjects:&#xD;
&#xD;
          -  Without chronic pathology requiring long-term treatment&#xD;
&#xD;
          -  Eosinophils between 0.1 and 0.4 G / L on recent blood test (&lt;3 months)&#xD;
&#xD;
        Exclusion Criteria for patients and controls:&#xD;
&#xD;
          -  Patient with an infection, state of emergency or progressive neoplastic pathology&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  History of atopy (allergic asthma, atopic eczema, allergic rhinitis, allergic&#xD;
             conjunctivitis)&#xD;
&#xD;
          -  Allergy to local anesthetics (for scleroderma patients only)&#xD;
&#xD;
          -  Taking into account a minimum weight of 50 kg and in the absence of cardiorespiratory&#xD;
             effects of scleroderma, only patients with at least 10 g of hemoglobin will be&#xD;
             included&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>66 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Guillaume Lefevre, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Lille</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Claude Huriez, CHU</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>January 21, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 25, 2019</study_first_posted>
  <last_update_submitted>March 10, 2021</last_update_submitted>
  <last_update_submitted_qc>March 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Eosinophil</keyword>
  <keyword>Fibrosis</keyword>
  <keyword>Systemic Scleroderma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Scleroderma, Systemic</mesh_term>
    <mesh_term>Scleroderma, Diffuse</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <!-- 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/NCT03816189
org study id: 2017_10
secondary id: 2017-A02587-46
nct id: NCT03816189
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Eosinophils are involved in tissue remodeling and fibrosis in many inflammatory diseases.
      Systemic sclerosis (SSc) is an autoimmune disease with fibrotic skin and lung complications.
      The profibrosing properties and data from the SSc literature suggest a possible role of the
      eosinophils in the process of fibrogenesis of SSc.
it will assess the activation state of blood eosinophils in SSc patients compared to healthy
      controls (ECP production in vitro, surface activation markers, whole transcriptome array,
      ..).

      it will also study skin eosinophils and their recruitment (extracellular eosinophil granules,
      eotaxins production in skin, ..)
observational model: Case-Control
time perspective: Prospective
measure: Comparison of ECP concentrations in supernatants of eosinophils culture
time frame: Baseline: one session
description: Eosinophils will be sorted, stimulated in vitro for 2 hours and ECP concentration will be assessed in supernatants
measure: Comparison of median fluorescence intensities of several surface markers on blood eosinophils, or comparison of percentages of positive cells among all eosinophils for a given marker (flow cytometry)
time frame: Baseline: one session
description: MFI/% of CD69, HLA class II, CD9, CD11c, CD44, CCR3, CRTH2, IL-5R on blood eosinophils
measure: Gene expression profiles will be compared between SSc patients and healthy controls (whole transcriptome assay)
time frame: Baseline: one session
description: Whole genome, transcriptomic approach (differentially expressed genes will be identified using a fold change cutoff)
measure: In skin biopsies: density of eosinophils, extracellular ECP and MBP deposits (absent in healthy skin), and density of eotaxin-1-producing cells will be assessed in damaged skin and apparently healthy skin of SSc patients
time frame: Baseline: one session
arm group label: Diffuse SSc
description: Recruitment of 20 patients with diffuse SSc
arm group label: Limited SSc
description: Recruitment of 20 patients with limited SSc
arm group label: Healthy subjects
description: Recruitment of 20 healthy subjects (control)
intervention type: Diagnostic Test
intervention name: Blood test
description: Patients in each group will have a blood sample (9x7 mL) for eosinophils isolation, study of activation markers on whole blood and serum biomarkers testing
arm group label: Diffuse SSc
arm group label: Healthy subjects
arm group label: Limited SSc
intervention type: Diagnostic Test
intervention name: Skin biopsies
description: In patients who will accept, skin biopsies will be performed in damaged and apparently normal skin, excluding fingers, hands, feet and face (biopsies are facultative)
arm group label: Diffuse SSc
arm group label: Limited SSc
Blood, Eosinophils, tissue
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 66 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Guillaume Lefevre, MD
role: Principal Investigator
affiliation: University Hospital, Lille
facility: 
country: France
responsible party type: Sponsor
mesh term: Scleroderma, Systemic
mesh term: Scleroderma, Diffuse
mesh term: Sclerosis