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/NCT06015256</url>
    </required_header>
    <id_info>
      <org_study_id>C21-75</org_study_id>
      <secondary_id>2022-A00651- 42</secondary_id>
      <nct_id>NCT06015256</nct_id>
    </id_info>
    <brief_title>NK Cells in Severe Asthma</brief_title>
    <acronym>NKAS</acronym>
    <official_title>Characterization of Natural Killer Cells in Severe Asthma Patients in Comparison With Control Subjects: Identification of Biomarkers, Response During Virus-induced Exacerbations, and Interaction With Bronchial Epithelial Cells</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Institut National de la Santé Et de la Recherche Médicale, France</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Asthma is a common chronic bronchial disease affecting 300 million people worldwide. The&#xD;
        disease can be severe when it is not managed properly or when it is not controlled by&#xD;
        treatments. Asthma is characterized by bronchial inflammation, bronchial hyperreactivity and&#xD;
        tissue remodeling. Symptoms include episodes of coughing, dyspnoea and wheezing in relation&#xD;
        with bronchial obstruction. The evolution is marked by the occurrence of exacerbations&#xD;
        (increase of symptoms), most often triggered by viral infections, mostly due to rhinoviruses.&#xD;
        The treatment of asthma is based on inhaled corticosteroid therapy sometimes combined with&#xD;
        other treatments that help control the majority of asthma. However, about 10% of patients&#xD;
        suffer from persistent symptoms despite these treatments.&#xD;
  &#xD;
        Natural killer (NK) cells are important actors of the antiviral innate immune response and&#xD;
        are present in high numbers in the lungs. However, their role in severe asthma and its&#xD;
        virus-induced exacerbations is unknown.&#xD;
  &#xD;
        The purpose of this work is to characterize NK cells in severe asthma in order to identify&#xD;
        molecules expressed differently from control subjects. The goal is to assess whether these&#xD;
        molecules could be potential biomarkers of a severe asthma subtype, also known as the&#xD;
        endotype, and/or be the molecular control for exacerbation. The advantage of identifying&#xD;
        biomarkers for inflammatory diseases lies in their usefulness in establishing a correct&#xD;
        diagnosis, monitoring the progress of the disease and the effectiveness of treatments. The&#xD;
        secondary objectives are to characterize the activation of NK cells in response to in vitro&#xD;
        rhinovirus infection of different types, in monoculture or in a model of interaction with a&#xD;
        bronchial epithelium, and identify one or more molecules involved in the interaction between&#xD;
        bronchial epithelial cells and NK cells.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2030</completion_date>
    <primary_completion_date type="Anticipated">September 2028</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>Changes in expression of one or more molecules on the surface of NK cells</measure>
      <time_frame>day 1 to day 2555</time_frame>
      <description>Rationale for choice of primary endpoint: Our aim is to phenotype NK cells in different groups of severe asthma patients compared with control subjects, in order to identify at least one marker of disease discrimination on these cells. We are therefore looking for previously unknown changes in the expression of one or more molecules.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Measurement of NK cell activation</measure>
      <time_frame>day 1 to day 2555</time_frame>
      <description>Change From Baseline in the expression of CD107, CD69 and interferon-ɣ.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Measurement of NK cell-induced epithelial cell activation and viability</measure>
      <time_frame>day 1 to day 2555</time_frame>
      <description>Change From Baseline in epithelial cell cohesion, mucin and cytokine (IL-8, type I interferon, IL-33 and TSLP) production</description>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">448</enrollment>
    <condition>Asthma Acute</condition>
    <arm_group>
      <arm_group_label>Severe uncontrolled asthma in exacerbation</arm_group_label>
      <arm_group_type>Other</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Severe uncontrolled asthma excluding exacerbation</arm_group_label>
      <arm_group_type>Other</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Severe controlled asthma</arm_group_label>
      <arm_group_type>Other</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Healthy volunteers (control group)</arm_group_label>
      <arm_group_type>Other</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>blood sample</intervention_name>
      <description>Blood sample (56mL) taken in a heparin tube</description>
      <arm_group_label>Healthy volunteers (control group)</arm_group_label>
      <arm_group_label>Severe controlled asthma</arm_group_label>
      <arm_group_label>Severe uncontrolled asthma excluding exacerbation</arm_group_label>
      <arm_group_label>Severe uncontrolled asthma in exacerbation</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Cases asthma controlled, uncontrolled excluding exacerbation, uncontrolled asthma&#xD;
          exacerbation, and healthy volunteers:&#xD;
  &#xD;
            -  Consent form read, understood, approved and signed before any study procedure&#xD;
  &#xD;
            -  Membership of a social security scheme or beneficiary of such a scheme&#xD;
  &#xD;
            -  Patient aged over 18&#xD;
  &#xD;
          Cases asthma controlled, uncontrolled excluding exacerbation, uncontrolled exacerbation:&#xD;
  &#xD;
          - Diagnosis of severe asthma confirmed by a respirologist at an expert centre&#xD;
  &#xD;
          Case asthma controlled:&#xD;
  &#xD;
          - Asthma control confirmed by a lung specialist from an expert centre&#xD;
  &#xD;
          Case uncontrolled asthma excluding exacerbation:&#xD;
  &#xD;
          - Uncontrolled asthma confirmed by a lung specialist from an expert centre&#xD;
  &#xD;
          Case uncontrolled asthma with exacerbation:&#xD;
  &#xD;
          - Current exacerbation&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          Cases asthma controlled, uncontrolled excluding exacerbation, uncontrolled asthma&#xD;
          exacerbation, and healthy volunteers:&#xD;
  &#xD;
            -  Person subject to a legal protection measure&#xD;
  &#xD;
            -  Vulnerable population: minors, persons under guardianship or trusteeship or persons&#xD;
               deprived of their rights to liberty by court order.&#xD;
  &#xD;
            -  women with a known pregnancy&#xD;
  &#xD;
            -  Inability or refusal to comply with research requirements&#xD;
  &#xD;
            -  Active or weaned smoker &gt; 15 PA&#xD;
  &#xD;
            -  Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or opioids in the 10&#xD;
               days prior to inclusion&#xD;
  &#xD;
          Case patient with asthma:&#xD;
  &#xD;
          - Coexistence of a chronic inflammatory disease other than asthma&#xD;
  &#xD;
          Case healthy volunteers:&#xD;
  &#xD;
          - Coexistence of an inflammatory pathology&#xD;
  &#xD;
          Exclusion criteria:&#xD;
  &#xD;
          Cases asthma: Pregnancy during follow-up Cases healthy volunteers: Total IgE level greater&#xD;
          than 100 kU/L (measured on the study sample)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Pascal Chanez, PU-PH</last_name>
      <phone>+334.91.96.58.64</phone>
      <email>pascal.chanez@univ-amu.fr</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Catherine Duez, CRCN</last_name>
      <phone>+334.91.32.42.74</phone>
      <email>catherine.duez@inserm.fr</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Hôpital NORD - AP-HM, Clinique des bronches, de l'allergie et du sommeil</name>
        <address>
          <city>Marseille</city>
          <zip>13915</zip>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Pascal CHANEZ, PU-PH</last_name>
        <phone>+334.91.96.58.64</phone>
        <email>pascal.chanez@univ-amu.fr</email>
      </contact>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 10, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</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>Asthma</mesh_term>
    </condition_browse>
    <!-- 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/NCT06015256
  org study id: C21-75
  secondary id: 2022-A00651- 42
  nct id: NCT06015256
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Asthma is a common chronic bronchial disease affecting 300 million people worldwide. The
        disease can be severe when it is not managed properly or when it is not controlled by
        treatments. Asthma is characterized by bronchial inflammation, bronchial hyperreactivity and
        tissue remodeling. Symptoms include episodes of coughing, dyspnoea and wheezing in relation
        with bronchial obstruction. The evolution is marked by the occurrence of exacerbations
        (increase of symptoms), most often triggered by viral infections, mostly due to rhinoviruses.
        The treatment of asthma is based on inhaled corticosteroid therapy sometimes combined with
        other treatments that help control the majority of asthma. However, about 10% of patients
        suffer from persistent symptoms despite these treatments.
  
        Natural killer (NK) cells are important actors of the antiviral innate immune response and
        are present in high numbers in the lungs. However, their role in severe asthma and its
        virus-induced exacerbations is unknown.
  
        The purpose of this work is to characterize NK cells in severe asthma in order to identify
        molecules expressed differently from control subjects. The goal is to assess whether these
        molecules could be potential biomarkers of a severe asthma subtype, also known as the
        endotype, and/or be the molecular control for exacerbation. The advantage of identifying
        biomarkers for inflammatory diseases lies in their usefulness in establishing a correct
        diagnosis, monitoring the progress of the disease and the effectiveness of treatments. The
        secondary objectives are to characterize the activation of NK cells in response to in vitro
        rhinovirus infection of different types, in monoculture or in a model of interaction with a
        bronchial epithelium, and identify one or more molecules involved in the interaction between
        bronchial epithelial cells and NK cells.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Changes in expression of one or more molecules on the surface of NK cells
  time frame: day 1 to day 2555
  description: Rationale for choice of primary endpoint: Our aim is to phenotype NK cells in different groups of severe asthma patients compared with control subjects, in order to identify at least one marker of disease discrimination on these cells. We are therefore looking for previously unknown changes in the expression of one or more molecules.
  measure: Measurement of NK cell activation
  time frame: day 1 to day 2555
  description: Change From Baseline in the expression of CD107, CD69 and interferon-ɣ.
  measure: Measurement of NK cell-induced epithelial cell activation and viability
  time frame: day 1 to day 2555
  description: Change From Baseline in epithelial cell cohesion, mucin and cytokine (IL-8, type I interferon, IL-33 and TSLP) production
  arm group label: Severe uncontrolled asthma in exacerbation
  arm group type: Other
  arm group label: Severe uncontrolled asthma excluding exacerbation
  arm group type: Other
  arm group label: Severe controlled asthma
  arm group type: Other
  arm group label: Healthy volunteers (control group)
  arm group type: Other
  intervention type: Biological
  intervention name: blood sample
  description: Blood sample (56mL) taken in a heparin tube
  arm group label: Healthy volunteers (control group)
  arm group label: Severe controlled asthma
  arm group label: Severe uncontrolled asthma excluding exacerbation
  arm group label: Severe uncontrolled asthma in exacerbation
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Pascal Chanez, PU-PH
  phone: +334.91.96.58.64
  email: pascal.chanez@univ-amu.fr
  last name: Catherine Duez, CRCN
  phone: +334.91.32.42.74
  email: catherine.duez@inserm.fr
  facility: 
  contact: 
  country: France
  responsible party type: Sponsor
  mesh term: Asthma