<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/NCT03231670</url>
  </required_header>
  <id_info>
    <org_study_id>RT-12</org_study_id>
    <nct_id>NCT03231670</nct_id>
  </id_info>
  <brief_title>Innate Immune Response of Blood Cells in Patients With Pneumonia</brief_title>
  <acronym>ASTRAL</acronym>
  <official_title>Analysis of Blood Cells Innate Immune Response in Patients With Lobar Pneumonia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lille Catholic University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut Pasteur de Lille</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Lille Catholic University</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>
      Pulmonary bacterial infections such as exacerbations of chronic bronchitis, nosocomial and&#xD;
      community-acquired pneumonia represent a major public health issue. Antibiotics have shown&#xD;
      their efficacy by direct antimicrobial activity and their limit particularly in case of&#xD;
      multidrug-resistant microorganisms or in treating patients with aggravating pathologies.&#xD;
      Innate immunity could be an alternative or complementary therapeutic pathway. Innate immunity&#xD;
      receptors bind universal and invariant microbial molecular patterns present in bacteria,&#xD;
      virus, fungus or parasite. Toll-like Receptors (TLR) activation by microbial agonist&#xD;
      stimulates the innate immunity response which results in the production of chemokines,&#xD;
      cytokines, antimicrobial molecules and the recruitment of innate cells.&#xD;
&#xD;
      The &quot; Pulmonary Infection and Innate Immunity &quot; team of the Immunity and Infection Center in&#xD;
      Lille (Group of Dr. Sirard and Carnoy) has a long expertise in the study of TLR5 and its&#xD;
      agonist, the flagellin, a structural protein of bacterial flagella. TLR5 is expressed on the&#xD;
      cell surface of macrophages, monocytes, dendritic and epithelial cells. Several studies in&#xD;
      mice have shown the flagellin prophylactic potential during bacterial infections through a&#xD;
      TLR5 dependent stimulation of innate immunity. Recently, the group of Dr. Sirard and Carnoy&#xD;
      has shown that flagellin can be used in association with antibiotics to treat Streptococcus&#xD;
      pneumoniae respiratory infections in mice. The results demonstrate that an agonist of TLR can&#xD;
      increase the therapeutic index of an antibiotic and improve the pulmonary anti-infectious&#xD;
      reaction. This innovative approach allows us to consider new antibacterial strategies where&#xD;
      antibiotics have reached their limit (nosocomial infection, multidrug-resistant bacteria…).&#xD;
      TLR agonists can activate multiple human cell type. Indeed, blood cells activation by TLR&#xD;
      agonists have been recently characterized in healthy volunteers.&#xD;
&#xD;
      However, there is no available data on the ability of TLR agonists to activate cells from&#xD;
      patients with infectious pneumopathies. A study in these patients is inevitable if one is to&#xD;
      consider the therapeutic use of agonists in respiratory pathologies.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 13, 2017</start_date>
  <completion_date type="Anticipated">September 2021</completion_date>
  <primary_completion_date type="Anticipated">October 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in IL-6 specific transcripts</measure>
    <time_frame>Baseline and 2 months</time_frame>
    <description>IL-6 specific transcripts will be measured in blood mononuclear cells after stimulation with a TLR5 agonist.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in expression of innate immunity genes after stimulation by TLR2 agonist</measure>
    <time_frame>Baseline and 2 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in expression of innate immunity genes after stimulation by TLR4 agonist</measure>
    <time_frame>Baseline and 2 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in expression of innate immunity genes after stimulation by TLR5 agonist</measure>
    <time_frame>Baseline and 2 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in expression of innate immunity genes after stimulation by TLR9 agonist</measure>
    <time_frame>Baseline and 2 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ELISA assay on mediators of inflammation with stimulation by TRL2 agonist</measure>
    <time_frame>Baseline and 2 months</time_frame>
    <description>ELISA assay on mediators of inflammation in the supernatant of blood mononuclear cells stimulated by TRL2 agonist</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ELISA assay on mediators of inflammation with stimulation by TRL4 agonist</measure>
    <time_frame>Baseline and 2 months</time_frame>
    <description>ELISA assay on mediators of inflammation in the supernatant of blood mononuclear cells stimulated by TRL4 agonist</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ELISA assay on mediators of inflammation with stimulation by TRL5 agonist</measure>
    <time_frame>Baseline and 2 months</time_frame>
    <description>ELISA assay on mediators of inflammation in the supernatant of blood mononuclear cells stimulated by TRL5 agonist</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ELISA assay on mediators of inflammation with stimulation by TRL9 agonist</measure>
    <time_frame>Baseline and 2 months</time_frame>
    <description>ELISA assay on mediators of inflammation in the supernatant of blood mononuclear cells stimulated by TRL9 agonist</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genotyping of TLR 2 gene</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genotyping of TLR 4 gene</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genotyping of TLR 5 gene</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genotyping of TLR 9 gene</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">38</enrollment>
  <condition>Lobar Pneumonia</condition>
  <arm_group>
    <arm_group_label>lobar pneumonia</arm_group_label>
    <description>Inpatient with lobar pneumonia will undergo a blood sampling during their hospitalization and after resolution of the infection (2 Months)</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood sampling</intervention_name>
    <description>5ml blood will be taken in addition to standard sampling</description>
    <arm_group_label>lobar pneumonia</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples 5ml&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Adult patient hospitalized in the department of pneumology for whom clinical, radiological&#xD;
        and biological criteria confirm the diagnosis of lobar pneumonia&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patient hospitalized in the department of pneumology for whom clinical,&#xD;
             radiological and biological criteria confirm the diagnosis of lobar pneumonia&#xD;
&#xD;
          -  Beneficiary of the French National Health Insurance Fund&#xD;
&#xD;
          -  Signed informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient under guardianship&#xD;
&#xD;
          -  Patient with acute respiratory distress syndrome or septic shock&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Patient with HIV, HCV or Mycobacterium tuberculosis&#xD;
&#xD;
          -  Transplanted patient receiving immunosuppressive therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christophe Carnoy, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Institut Pasteur de Lille</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jean-Claude Sirard, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Institut Pasteur de Lille</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Amélie Lansiaux, MD, PhD</last_name>
    <phone>03 20 22 52 69</phone>
    <phone_ext>+33</phone_ext>
    <email>lansiaux.amelie@ghicl.net</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jean-Jacques Vitagliano, PhD</last_name>
    <phone>03 20 22 57 51</phone>
    <email>vitagliano.jean-jacques@ghicl.net</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hôpital Saint-Philibert</name>
      <address>
        <city>Lomme</city>
        <state>Hauts De France</state>
        <zip>59000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anne-France Georgel</last_name>
    </contact>
    <investigator>
      <last_name>Philippe Delecluse, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nicolas Masson, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2017</study_first_posted>
  <last_update_submitted>August 20, 2018</last_update_submitted>
  <last_update_submitted_qc>August 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</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/NCT03231670
org study id: RT-12
nct id: NCT03231670
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Pulmonary bacterial infections such as exacerbations of chronic bronchitis, nosocomial and
      community-acquired pneumonia represent a major public health issue. Antibiotics have shown
      their efficacy by direct antimicrobial activity and their limit particularly in case of
      multidrug-resistant microorganisms or in treating patients with aggravating pathologies.
      Innate immunity could be an alternative or complementary therapeutic pathway. Innate immunity
      receptors bind universal and invariant microbial molecular patterns present in bacteria,
      virus, fungus or parasite. Toll-like Receptors (TLR) activation by microbial agonist
      stimulates the innate immunity response which results in the production of chemokines,
      cytokines, antimicrobial molecules and the recruitment of innate cells.

      The " Pulmonary Infection and Innate Immunity " team of the Immunity and Infection Center in
      Lille (Group of Dr. Sirard and Carnoy) has a long expertise in the study of TLR5 and its
      agonist, the flagellin, a structural protein of bacterial flagella. TLR5 is expressed on the
      cell surface of macrophages, monocytes, dendritic and epithelial cells. Several studies in
      mice have shown the flagellin prophylactic potential during bacterial infections through a
      TLR5 dependent stimulation of innate immunity. Recently, the group of Dr. Sirard and Carnoy
      has shown that flagellin can be used in association with antibiotics to treat Streptococcus
      pneumoniae respiratory infections in mice. The results demonstrate that an agonist of TLR can
      increase the therapeutic index of an antibiotic and improve the pulmonary anti-infectious
      reaction. This innovative approach allows us to consider new antibacterial strategies where
      antibiotics have reached their limit (nosocomial infection, multidrug-resistant bacteria…).
      TLR agonists can activate multiple human cell type. Indeed, blood cells activation by TLR
      agonists have been recently characterized in healthy volunteers.

      However, there is no available data on the ability of TLR agonists to activate cells from
      patients with infectious pneumopathies. A study in these patients is inevitable if one is to
      consider the therapeutic use of agonists in respiratory pathologies.
observational model: Case-Only
time perspective: Prospective
measure: Change in IL-6 specific transcripts
time frame: Baseline and 2 months
description: IL-6 specific transcripts will be measured in blood mononuclear cells after stimulation with a TLR5 agonist.
measure: Change in expression of innate immunity genes after stimulation by TLR2 agonist
time frame: Baseline and 2 months
measure: Change in expression of innate immunity genes after stimulation by TLR4 agonist
time frame: Baseline and 2 months
measure: Change in expression of innate immunity genes after stimulation by TLR5 agonist
time frame: Baseline and 2 months
measure: Change in expression of innate immunity genes after stimulation by TLR9 agonist
time frame: Baseline and 2 months
measure: Change in ELISA assay on mediators of inflammation with stimulation by TRL2 agonist
time frame: Baseline and 2 months
description: ELISA assay on mediators of inflammation in the supernatant of blood mononuclear cells stimulated by TRL2 agonist
measure: Change in ELISA assay on mediators of inflammation with stimulation by TRL4 agonist
time frame: Baseline and 2 months
description: ELISA assay on mediators of inflammation in the supernatant of blood mononuclear cells stimulated by TRL4 agonist
measure: Change in ELISA assay on mediators of inflammation with stimulation by TRL5 agonist
time frame: Baseline and 2 months
description: ELISA assay on mediators of inflammation in the supernatant of blood mononuclear cells stimulated by TRL5 agonist
measure: Change in ELISA assay on mediators of inflammation with stimulation by TRL9 agonist
time frame: Baseline and 2 months
description: ELISA assay on mediators of inflammation in the supernatant of blood mononuclear cells stimulated by TRL9 agonist
measure: Genotyping of TLR 2 gene
time frame: Baseline
measure: Genotyping of TLR 4 gene
time frame: Baseline
measure: Genotyping of TLR 5 gene
time frame: Baseline
measure: Genotyping of TLR 9 gene
time frame: Baseline
arm group label: lobar pneumonia
description: Inpatient with lobar pneumonia will undergo a blood sampling during their hospitalization and after resolution of the infection (2 Months)
intervention type: Procedure
intervention name: Blood sampling
description: 5ml blood will be taken in addition to standard sampling
arm group label: lobar pneumonia
Blood samples 5ml
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Christophe Carnoy, PhD
role: Study Director
affiliation: Institut Pasteur de Lille
last name: Jean-Claude Sirard, PhD
role: Study Director
affiliation: Institut Pasteur de Lille
last name: Amélie Lansiaux, MD, PhD
phone: 03 20 22 52 69
phone ext: +33
email: lansiaux.amelie@ghicl.net
last name: Jean-Jacques Vitagliano, PhD
phone: 03 20 22 57 51
email: vitagliano.jean-jacques@ghicl.net
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Pneumonia