<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/NCT03231995</url>
  </required_header>
  <id_info>
    <org_study_id>69HCL17_0175</org_study_id>
    <secondary_id>2017-A03035-48</secondary_id>
    <nct_id>NCT03231995</nct_id>
  </id_info>
  <brief_title>Biomarkers for the Prognosis of Influenza in Children</brief_title>
  <acronym>BMIG</acronym>
  <official_title>Prospective Multicentre Study to Determine Respiratory Microbiome Biomarkers for the Prognostic of Clinical Course of Influenza in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</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>
      Context: Seasonal influenza affects 2.5 to 3 million people each year in France, resulting in&#xD;
      1500 to 2000 severe cases seen in intensive care units. The severity of influenza is related&#xD;
      to, among other things, its respiratory or neurological complications, observed especially in&#xD;
      children. Early determination of the severity of influenza is a critical step to avoid in&#xD;
      appropriate treatment and care for patients and to improve their survival. Viral, human but&#xD;
      also environmental factors have been described as having an important role in determining&#xD;
      this severity. Several studies suggest that the nasopharyngeal microbiome may be involved in&#xD;
      the incidence and severity of respiratory viral infections. During influenza infection, the&#xD;
      respiratory microbiota is significantly altered. In animal models, particularly murine&#xD;
      models, the microbiota regulates the immune response to influenza virus infection. In a&#xD;
      retrospective preliminary study, the investigators showed that the composition of the&#xD;
      nasopharyngeal bacterial microbiota is different between children who develop a severe or&#xD;
      moderate influenza. This difference was observed on respiratory specimens at admission to&#xD;
      pediatric emergencies within two days of onset of symptoms.&#xD;
&#xD;
      Hypotheses :&#xD;
&#xD;
        -  The respiratory microbiome is a determining factor in the clinical course of influenza&#xD;
           infection (benign vs. severe with respiratory or neurological complication)&#xD;
&#xD;
        -  The respiratory microbiome can be used as a prognostic biomarker of the clinical course&#xD;
           of influenza Originality: There are currently no clinical and / or virological markers&#xD;
           to predict the clinical course of influenza infection. This study will define biomarkers&#xD;
           of the respiratory microbiome to discriminate patients who will develop a severe&#xD;
           influenza from those who will develop a moderate influenza. These prognostic biomarkers&#xD;
           could be used to rapidly refer patients at risk to intensive care units, thus improving&#xD;
           patient management and care. Moreover, at the fundamental level, this study will specify&#xD;
           the role of the microbiome in the severity of influenza infection.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 15, 2019</start_date>
  <completion_date type="Actual">April 20, 2022</completion_date>
  <primary_completion_date type="Actual">April 20, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Definition and evaluation of a microbial signature discriminating patients developing severe influenza from those developing moderate influenza</measure>
    <time_frame>Day 30</time_frame>
    <description>On nasopharyngeal specimen collected at inclusion, a microbial signature will be defined as a limited number of bacterial genomic groups (OTU Operational Taxonomic Unit), that will help discriminate the 2 groups of patients (evolution toward a severe or a moderate influenza, evaluated at hospital discharge).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>sequencing the hypervariable regions of the 16S RNA on the longitudinal respiratory specimens</measure>
    <time_frame>Day 1</time_frame>
    <description>We will analyze the different dynamics of the composition of the microbiome associated with different influenza evolutions. The qualitative and quantitative evolution of the microbial species present in the respiratory specimens will be evaluated by sequencing the hypervariable regions of the 16S RNA on the longitudinal respiratory specimens performed on Day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>sequencing the hypervariable regions of the 16S RNA on the longitudinal respiratory specimens</measure>
    <time_frame>Day 2</time_frame>
    <description>We will analyze the different dynamics of the composition of the microbiome associated with different influenza evolutions. The qualitative and quantitative evolution of the microbial species present in the respiratory specimens will be evaluated by sequencing the hypervariable regions of the 16S RNA on the longitudinal respiratory specimens performed on day 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>sequencing the hypervariable regions of the 16S RNA on the longitudinal respiratory specimens</measure>
    <time_frame>Day 5</time_frame>
    <description>We will analyze the different dynamics of the composition of the microbiome associated with different influenza evolutions. The qualitative and quantitative evolution of the microbial species present in the respiratory specimens will be evaluated by sequencing the hypervariable regions of the 16S RNA on the longitudinal respiratory specimens performed on day 5</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">145</enrollment>
  <condition>Influenza</condition>
  <arm_group>
    <arm_group_label>Respiratory microbiome biomarkers</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Collection of nasopharyngeal specimen collected at D0, D1, D2 and D5.</intervention_name>
    <description>Analyses will be performed on nasopharyngeal specimen collected at D0, D1, D2 and D5.&#xD;
Definition and validation of nasopharyngeal microbiome biomarkers (bacterial, viral, transcriptomic signature)</description>
    <arm_group_label>Respiratory microbiome biomarkers</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 5 years&#xD;
&#xD;
          -  Seen in an emergency department with influenza confirmed by a positive test&#xD;
             (polumerase chain reaction, rapide antigen detection test).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of associated significant comorbidity (chronic respiratory, cardiac,&#xD;
             neurological or metabolic pathology, prematurity, known immunodeficiency)&#xD;
&#xD;
          -  Documented non-respiratory bacterial infection&#xD;
&#xD;
          -  No consent&#xD;
&#xD;
          -  Patient not affiliated to a national health cover&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>5 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>CIC groupement Hospitalier Est - Hospices Civils de Lyon</name>
      <address>
        <city>Lyon</city>
        <zip>69317</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Nord</name>
      <address>
        <city>Saint-Étienne</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>July 25, 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>June 7, 2022</last_update_submitted>
  <last_update_submitted_qc>June 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Severe influenza</keyword>
  <keyword>biomarkers</keyword>
  <keyword>respiratory microbiome</keyword>
  <keyword>prognosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</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/NCT03231995
org study id: 69HCL17_0175
secondary id: 2017-A03035-48
nct id: NCT03231995
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Context: Seasonal influenza affects 2.5 to 3 million people each year in France, resulting in
      1500 to 2000 severe cases seen in intensive care units. The severity of influenza is related
      to, among other things, its respiratory or neurological complications, observed especially in
      children. Early determination of the severity of influenza is a critical step to avoid in
      appropriate treatment and care for patients and to improve their survival. Viral, human but
      also environmental factors have been described as having an important role in determining
      this severity. Several studies suggest that the nasopharyngeal microbiome may be involved in
      the incidence and severity of respiratory viral infections. During influenza infection, the
      respiratory microbiota is significantly altered. In animal models, particularly murine
      models, the microbiota regulates the immune response to influenza virus infection. In a
      retrospective preliminary study, the investigators showed that the composition of the
      nasopharyngeal bacterial microbiota is different between children who develop a severe or
      moderate influenza. This difference was observed on respiratory specimens at admission to
      pediatric emergencies within two days of onset of symptoms.

      Hypotheses :

        -  The respiratory microbiome is a determining factor in the clinical course of influenza
           infection (benign vs. severe with respiratory or neurological complication)

        -  The respiratory microbiome can be used as a prognostic biomarker of the clinical course
           of influenza Originality: There are currently no clinical and / or virological markers
           to predict the clinical course of influenza infection. This study will define biomarkers
           of the respiratory microbiome to discriminate patients who will develop a severe
           influenza from those who will develop a moderate influenza. These prognostic biomarkers
           could be used to rapidly refer patients at risk to intensive care units, thus improving
           patient management and care. Moreover, at the fundamental level, this study will specify
           the role of the microbiome in the severity of influenza infection.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Definition and evaluation of a microbial signature discriminating patients developing severe influenza from those developing moderate influenza
time frame: Day 30
description: On nasopharyngeal specimen collected at inclusion, a microbial signature will be defined as a limited number of bacterial genomic groups (OTU Operational Taxonomic Unit), that will help discriminate the 2 groups of patients (evolution toward a severe or a moderate influenza, evaluated at hospital discharge).
measure: sequencing the hypervariable regions of the 16S RNA on the longitudinal respiratory specimens
time frame: Day 1
description: We will analyze the different dynamics of the composition of the microbiome associated with different influenza evolutions. The qualitative and quantitative evolution of the microbial species present in the respiratory specimens will be evaluated by sequencing the hypervariable regions of the 16S RNA on the longitudinal respiratory specimens performed on Day 1.
measure: sequencing the hypervariable regions of the 16S RNA on the longitudinal respiratory specimens
time frame: Day 2
description: We will analyze the different dynamics of the composition of the microbiome associated with different influenza evolutions. The qualitative and quantitative evolution of the microbial species present in the respiratory specimens will be evaluated by sequencing the hypervariable regions of the 16S RNA on the longitudinal respiratory specimens performed on day 2
measure: sequencing the hypervariable regions of the 16S RNA on the longitudinal respiratory specimens
time frame: Day 5
description: We will analyze the different dynamics of the composition of the microbiome associated with different influenza evolutions. The qualitative and quantitative evolution of the microbial species present in the respiratory specimens will be evaluated by sequencing the hypervariable regions of the 16S RNA on the longitudinal respiratory specimens performed on day 5
arm group label: Respiratory microbiome biomarkers
arm group type: Experimental
intervention type: Biological
intervention name: Collection of nasopharyngeal specimen collected at D0, D1, D2 and D5.
description: Analyses will be performed on nasopharyngeal specimen collected at D0, D1, D2 and D5.
Definition and validation of nasopharyngeal microbiome biomarkers (bacterial, viral, transcriptomic signature)
arm group label: Respiratory microbiome biomarkers
criteria: 
gender: All
minimum age: N/A
maximum age: 5 Years
healthy volunteers: No
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Influenza, Human