xml: <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/NCT05972213</url>
    </required_header>
    <id_info>
      <org_study_id>APHP230345</org_study_id>
      <nct_id>NCT05972213</nct_id>
    </id_info>
    <brief_title>Phenotypic and Functional Characterization of Neutrophils and Eosinophils in Severe Asthma Treated With Biotherapy</brief_title>
    <acronym>CaPHe</acronym>
    <official_title>Phenotypic and Functional Characterization of Neutrophils and Eosinophils in Severe Asthma Treated With Biotherapy</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        Neutrophils and eosinophils can have different functions. Depending on their environment,&#xD;
        they can be more or less active, with more or less inflammatory activity.&#xD;
  &#xD;
        Biotherapies can reduce the number of inflammatory cells in the blood and bronchi. However,&#xD;
        it is not known whether they have the ability to modify the functions of the remaining cells.&#xD;
  &#xD;
        The aim of this study is to better understand the functioning of eosinophilic and neutrophil&#xD;
        polynuclear drugs involved in the response to biotherapies in severe asthma. The hypothesis&#xD;
        is that biotherapies modify the inflammatory functions of polynuclear cells, which would&#xD;
        contribute to the effect of the drug on asthma.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Between 3 and 10% of adult asthmatics have a severe form of the disease. The pathophysiology&#xD;
        of asthma is dominated by chronic bronchial inflammation of type &quot;T2&quot;&quot; with eosinophil&#xD;
        infiltration whose role in bronchial reshuffling, hyperresponsiveness and maintenance of&#xD;
        inflammation has been well documented. They are specifically targeted by monoclonal&#xD;
        antibodies to IL (inter leukin)-5, IL-5R and IL-4/13.&#xD;
  &#xD;
        There is a population of severe asthmatics called &quot;non-T2&quot; characterized by Th17&#xD;
        inflammation, production of IL-6, IL-8, IL-11, GM-CSF (Granulocyte-macrophage&#xD;
        colony-stimulating factor) and IL-17 and preponderant bronchial recruitment of neutrophils,&#xD;
        resulting in greater clinical severity and decreased sensitivity to corticosteroids.&#xD;
        Neutrophils, not specifically targeted by the current therapies used, release reactive forms&#xD;
        of oxygen, proteases, neutrophil extracellular traps (NETs) contributing to airway&#xD;
        inflammation. The phenotypic heterogeneity, functional heterogeneity and plasticity of&#xD;
        neutrophils has been studied in other pathologies but not specifically in asthma.&#xD;
  &#xD;
        The response to biotherapies is not always optimal with a significant number of failures or&#xD;
        escapes in clinical practice.&#xD;
  &#xD;
        There are limited data on these eosinophilic and neutrophil leukocyte subpopulations in&#xD;
        asthma, including phenotypic changes under biotherapies. Cellular functions have not been&#xD;
        studied under treatment and clinical response is unknown. In addition, neutrophils and&#xD;
        eosinophils are most often studied separately, while both cell types contribute to&#xD;
        inflammation and can regulate each other.&#xD;
  &#xD;
        This study hypothesize an impact of severe asthma biotherapies on the subpopulations and&#xD;
        functionality of polynuclear drugs, contributing to the observed therapeutic effect.&#xD;
  &#xD;
        This work could lead to a better understanding of the mechanisms of response to biotherapies.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 1, 2023</start_date>
    <completion_date type="Anticipated">May 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">May 1, 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Measurement of the difference between the studied parameters of polynuclear cells measured at 6 months compared to those measured at the start of biotherapy.</measure>
      <time_frame>3 months for the longitudinal group and 9 months for the cross-sectional group</time_frame>
      <description>The main objective will be to characterize the longitudinal evolution of markers measured at 6 months after initiation of biotherapy.&#xD;
  These parameters will be studied on a fresh blood sample collected peripherally on a 7 mL EDTA (Ethylenediaminetetraacetic acid) tube and 5 mL dry tube on the day of inclusion at the time of day hospital or pulmonology consultation, before initiation and during a follow-up pneumology consultation/day hospital at 6 months post-initiation.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Measure the level of asthma control 6 months after the start of treatment, defined by the ACT score</measure>
      <time_frame>3 months for the longitudinal group and 9 months for the cross-sectional group</time_frame>
      <description>Secondary objectives will be to measure an association of markers</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Measure the number of exacerbations in the previous 6 months</measure>
      <time_frame>3 months for the longitudinal group and 9 months for the cross-sectional group</time_frame>
      <description>Secondary objectives will be to measure an association of markers</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Measure the type of biotherapy used</measure>
      <time_frame>3 months for the longitudinal group and 9 months for the cross-sectional group</time_frame>
      <description>Secondary objectives will be to measure an association of markers</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">105</enrollment>
    <condition>Asthma</condition>
    <arm_group>
      <arm_group_label>Longitudinal group</arm_group_label>
      <description>25 patients anticipated. Patients with :&#xD;
  Uncontrolled asthma: ACT score &lt; 20 and/or at least one exacerbation in the last 6 months&#xD;
  Naïve biotherapy&#xD;
  Indication for initiation of biotherapy according to the referring pulmonologist (omalizumab, mepolizumab, benralizumab, dupilumab)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cross-sectional group</arm_group_label>
      <description>80 patients anticipated.&#xD;
  Patient on biotherapy (omalizumab, mepolizumab, benralizumab, dupilumab) for at least 6 months.&#xD;
  Controlled asthma (ACT &gt; 20 and no exacerbation for 6 months) or uncontrolled asthma (ACT &lt; 20 and/or at least 1 exacerbation for 6 months).</description>
    </arm_group>
    <biospec_retention>Samples Without DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        1 ml of serum&#xD;
  &#xD;
        1ml of plasma&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Severe asthmatic patients followed in the Pneumology A department at Bichat Hospital.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  18 years ≤ Age &lt; 85 years&#xD;
  &#xD;
            -  Severe asthma as defined by ERS/ATS (European Respiratory Society/American Thoracic&#xD;
               Society) 2014: asthma requiring high doses of ICS (inhaled corticosteroid) combined&#xD;
               with another control therapy (such as long-acting bronchodilators), whether or not&#xD;
               patients are controlled&#xD;
  &#xD;
          Longitudinal group:&#xD;
  &#xD;
            -  Uncontrolled asthma: ACT score &lt; 20 and/or at least one exacerbation in the last 6&#xD;
               months&#xD;
  &#xD;
            -  Naïve about biotherapy&#xD;
  &#xD;
            -  Indication for the initiation of biotherapy according to the referring pulmonologist&#xD;
               (omalizumab, mepolizumab, benralizumab, dupilumab)&#xD;
  &#xD;
          Cross-sectional group:&#xD;
  &#xD;
            -  Patient on biotherapy (omalizumab, mepolizumab, benralizumab, dupilumab) for at least&#xD;
               6 months.&#xD;
  &#xD;
            -  Controlled asthma (ACT &gt; 20 and no exacerbation for 6 months) or uncontrolled asthma&#xD;
               (ACT &lt; 20 and/or at least 1 exacerbation for 6 months).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Refusal to participate or opposition to data processing&#xD;
  &#xD;
            -  Patient under guardianship or with curators&#xD;
  &#xD;
            -  Patient on immunosuppressant (other than corticosteroids)&#xD;
  &#xD;
            -  Treatment with biotherapy for another indication&#xD;
  &#xD;
            -  Patient not affiliated to a social security scheme or state medical aid&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>85 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Camille Taillé, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Camille Taillé, MD, PhD</last_name>
      <phone>01 40 25 68 63</phone>
      <email>camille.taille@aphp.fr</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Luc De Chaisemartin, MD</last_name>
      <phone>01 40 25 85 21</phone>
      <email>luc.de-chaisemartin@aphp.fr</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Hôpital Bichat-Claude Bernard</name>
        <address>
          <city>Paris</city>
          <zip>75018</zip>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Camille Taillé, MD, PhD</last_name>
        <phone>01 40 25 68 63</phone>
        <email>camille.taille@aphp.fr</email>
      </contact>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 4, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>July 25, 2023</last_update_submitted>
    <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 2, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>severe asthma</keyword>
    <keyword>biotherapies</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Asthma</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05972213
  org study id: APHP230345
  nct id: NCT05972213
  lead sponsor: 
  has dmc: No
  Neutrophils and eosinophils can have different functions. Depending on their environment,
        they can be more or less active, with more or less inflammatory activity.
  
        Biotherapies can reduce the number of inflammatory cells in the blood and bronchi. However,
        it is not known whether they have the ability to modify the functions of the remaining cells.
  
        The aim of this study is to better understand the functioning of eosinophilic and neutrophil
        polynuclear drugs involved in the response to biotherapies in severe asthma. The hypothesis
        is that biotherapies modify the inflammatory functions of polynuclear cells, which would
        contribute to the effect of the drug on asthma.
  Between 3 and 10% of adult asthmatics have a severe form of the disease. The pathophysiology
        of asthma is dominated by chronic bronchial inflammation of type "T2"" with eosinophil
        infiltration whose role in bronchial reshuffling, hyperresponsiveness and maintenance of
        inflammation has been well documented. They are specifically targeted by monoclonal
        antibodies to IL (inter leukin)-5, IL-5R and IL-4/13.
  
        There is a population of severe asthmatics called "non-T2" characterized by Th17
        inflammation, production of IL-6, IL-8, IL-11, GM-CSF (Granulocyte-macrophage
        colony-stimulating factor) and IL-17 and preponderant bronchial recruitment of neutrophils,
        resulting in greater clinical severity and decreased sensitivity to corticosteroids.
        Neutrophils, not specifically targeted by the current therapies used, release reactive forms
        of oxygen, proteases, neutrophil extracellular traps (NETs) contributing to airway
        inflammation. The phenotypic heterogeneity, functional heterogeneity and plasticity of
        neutrophils has been studied in other pathologies but not specifically in asthma.
  
        The response to biotherapies is not always optimal with a significant number of failures or
        escapes in clinical practice.
  
        There are limited data on these eosinophilic and neutrophil leukocyte subpopulations in
        asthma, including phenotypic changes under biotherapies. Cellular functions have not been
        studied under treatment and clinical response is unknown. In addition, neutrophils and
        eosinophils are most often studied separately, while both cell types contribute to
        inflammation and can regulate each other.
  
        This study hypothesize an impact of severe asthma biotherapies on the subpopulations and
        functionality of polynuclear drugs, contributing to the observed therapeutic effect.
  
        This work could lead to a better understanding of the mechanisms of response to biotherapies.
  observational model: Cohort
  time perspective: Prospective
  measure: Measurement of the difference between the studied parameters of polynuclear cells measured at 6 months compared to those measured at the start of biotherapy.
  time frame: 3 months for the longitudinal group and 9 months for the cross-sectional group
  description: The main objective will be to characterize the longitudinal evolution of markers measured at 6 months after initiation of biotherapy.
  These parameters will be studied on a fresh blood sample collected peripherally on a 7 mL EDTA (Ethylenediaminetetraacetic acid) tube and 5 mL dry tube on the day of inclusion at the time of day hospital or pulmonology consultation, before initiation and during a follow-up pneumology consultation/day hospital at 6 months post-initiation.
  measure: Measure the level of asthma control 6 months after the start of treatment, defined by the ACT score
  time frame: 3 months for the longitudinal group and 9 months for the cross-sectional group
  description: Secondary objectives will be to measure an association of markers
  measure: Measure the number of exacerbations in the previous 6 months
  time frame: 3 months for the longitudinal group and 9 months for the cross-sectional group
  description: Secondary objectives will be to measure an association of markers
  measure: Measure the type of biotherapy used
  time frame: 3 months for the longitudinal group and 9 months for the cross-sectional group
  description: Secondary objectives will be to measure an association of markers
  arm group label: Longitudinal group
  description: 25 patients anticipated. Patients with :
  Uncontrolled asthma: ACT score < 20 and/or at least one exacerbation in the last 6 months
  Naïve biotherapy
  Indication for initiation of biotherapy according to the referring pulmonologist (omalizumab, mepolizumab, benralizumab, dupilumab)
  arm group label: Cross-sectional group
  description: 80 patients anticipated.
  Patient on biotherapy (omalizumab, mepolizumab, benralizumab, dupilumab) for at least 6 months.
  Controlled asthma (ACT > 20 and no exacerbation for 6 months) or uncontrolled asthma (ACT < 20 and/or at least 1 exacerbation for 6 months).
  1 ml of serum
  
        1ml of plasma
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 85 Years
  healthy volunteers: No
  last name: Camille Taillé, MD, PhD
  role: Principal Investigator
  affiliation: Assistance Publique - Hôpitaux de Paris
  last name: Camille Taillé, MD, PhD
  phone: 01 40 25 68 63
  email: camille.taille@aphp.fr
  last name: Luc De Chaisemartin, MD
  phone: 01 40 25 85 21
  email: luc.de-chaisemartin@aphp.fr
  facility: 
  contact: 
  country: France
  responsible party type: Sponsor
  mesh term: Asthma
  sharing ipd: No