<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/NCT04494308</url>
  </required_header>
  <id_info>
    <org_study_id>RP 06/18</org_study_id>
    <nct_id>NCT04494308</nct_id>
  </id_info>
  <brief_title>Evaluation of Eosinophil Phenotype in COPD Patients</brief_title>
  <acronym>V-FEO</acronym>
  <official_title>Pilot Study for Evaluation of Eosinophils Phenotype and Activation Status in COPD Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>IRCCS San Raffaele</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>IRCCS San Raffaele</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This is a pilot non pharmacological observational study. Aim of the study is to analyze the&#xD;
      immunophenotype of circulating eosinophils in chronic obstructive pulmonary disease (COPD)&#xD;
      patients, and to correlate results with clinical status of patients (stable versus&#xD;
      exacerbated patients, response to therapy). In about 30% of COPD patients there is an&#xD;
      increase in the number of circulating eosinophils, which associates with an increased risk&#xD;
      for exacerbation. However, no data is available on the role of eosinophils in this disease,&#xD;
      on their activation status and their response to chemotactic factors. By multicolor flow&#xD;
      cytometry the investigators will analyze membrane molecules and intracellular cytokines&#xD;
      associated to chemotaxis, degranulation and inflammation. The study will enroll 30 patients&#xD;
      (15 stable and 15 with exacerbation). Results will be analyzed taking into account clinical&#xD;
      status,disease progression and response to treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In about 30% of COPD patients there is an increased number of circulating eosinophils. On&#xD;
      their membrane, eosinophils express several molecules, also related to their physiology,&#xD;
      namely major histocompatibility complex (MHC) class II, needed for antigen presentation;&#xD;
      CCR3, receptor for a variety of chemokines, including eotaxin (CCL11), eotaxin-3 (CCL26),&#xD;
      monocyte chemotactict protein (MCP)-3 (CCL7), MCP-4 (CCL13), and RANTES (CCL5); cluster of&#xD;
      differentiation (CD)125, which binds IL-5 and stimulates eosinophils proliferation; CD63, a&#xD;
      marker that is upregulated after eosinophils degranulation; and CD294 (CRTH2) which is the&#xD;
      prostaglandin D2 receptor, and is associated to allergy and inflammation . The hypothesis for&#xD;
      the present trial is that different clinical phenotypes of COPD patients could be associated&#xD;
      to different activation statuses of eosinophils, that can be evaluated analyzing by flow&#xD;
      cytometry the membrane expression of the above mentioned molecules. In particular, the&#xD;
      investigators hypothesize that membrane molecules may be modulated in different stages of the&#xD;
      diseases, and may change after medical and rehabilitative therapies.&#xD;
&#xD;
      The investigators will analyze phenotype of eosinophils from blood samples of patients with&#xD;
      COPD, admitted to the hospital after an episode of exacerbation, or for routine controls. In&#xD;
      this way, the association between a particular pattern of molecules expressed on eosinophils&#xD;
      membrane and the severity of COPD will be defined. Moreover, for hospitalized patients,&#xD;
      eosinophils phenotype also on discharge day will be analyzed. In this way the effect of&#xD;
      therapies on eosinophils activation will be assessed. Clinical status of patients will be&#xD;
      assessed by standard tests such as St George Respiratory Questionnaire (SGRQ), BODE index,&#xD;
      COPD Assessment Test (CAT), Six min. Walking Test (6'WT), Pulmonary Function Tests (PFT).&#xD;
&#xD;
      Eosinophils phenotype and in vitro cytokines production will be analyzed by multicolor flow&#xD;
      cytometry. To minimize the effect of manipulation, staining of membrane molecules will be&#xD;
      performed on whole blood samples, followed by lysis of erythrocytes. The following molecules&#xD;
      will be analyzed: CD45, CD16, CD15, CD63, CCR3, CD125, CD294, Siglec-8. After in vitro&#xD;
      stimulation with lipopolysaccharide (LPS) or CCL11, the production of interleukine (IL)-4,&#xD;
      TGFbeta and IL-2 will be analyzed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 19, 2019</start_date>
  <completion_date type="Anticipated">July 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Association of eosinophils phenotype with clinical status in COPD patients</measure>
    <time_frame>one year</time_frame>
    <description>We expect to identify different patterns of expression of molecules on eosinophils membrane that are associated with different clinical phenotypes of COPD patients. We will also associate eosinophils phenotype to the response to medical and rehabilitation therapy. The definition of these patterns will provide a diagnostic tool to rapidly identify patients that will benefit from a specific therapy</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">30</enrollment>
  <condition>COPD</condition>
  <condition>COPD Exacerbation</condition>
  <arm_group>
    <arm_group_label>exacerbated</arm_group_label>
    <description>COPD patients admitted to the hospital for an exacerbation occurred within the past 10 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>stable</arm_group_label>
    <description>COPD stable patients with no exacerbations in the past 3 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>biomarker identification</intervention_name>
    <description>flow cytometric analysis of eosinophils membrane molecules</description>
    <arm_group_label>exacerbated</arm_group_label>
    <arm_group_label>stable</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        30 COPD patients, of which 15 will be COPD patients admitted to the Pulmonary&#xD;
        Rehabilitation Unit of IRCCS San Raffaele Pisana hospital for an exacerbation occurred&#xD;
        within the past 10 days (exacerbated cohort); the other 15 will be stable patients, (no&#xD;
        exacerbations in the past 3 months- stable cohort), affering to the hospital as outpatients&#xD;
        for routine controls&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  COPD&#xD;
&#xD;
          -  percentage of eosinophils &gt;0%&#xD;
&#xD;
          -  episode of exacerbation in the previous 10 days (for exacerbated cohort)&#xD;
&#xD;
          -  no exacerbation in the previous 3 months (for stable cohort)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  percentage of eosinophils =0%&#xD;
&#xD;
          -  history of allergic diseases&#xD;
&#xD;
          -  patients that are currently enrolled in other clinical trials involving new drugs or&#xD;
             treatments&#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>Laura Vitiello, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>IRCCS San Raffaele Pisana, Roma</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Vittorio Cardaci, MD</last_name>
    <phone>+39 0666052336</phone>
    <email>vittorio.cardaci@sanraffaele.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Laura Vitiello, PhD</last_name>
    <phone>+39 0652253440</phone>
    <email>laura.vitiello@sanraffaele.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>IRCCS San Raffaele Pisana</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00166</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vittorio Cardaci, MD</last_name>
      <phone>+39 0666052336</phone>
      <email>vittorio.cardaci@sanraffaele.it</email>
    </contact>
    <contact_backup>
      <last_name>laura Vitiello, PhD</last_name>
      <phone>+39 06 52253440</phone>
      <email>laura.vitiello@sanraffaele.it</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>February 15, 2021</last_update_submitted>
  <last_update_submitted_qc>February 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>IRCCS San Raffaele</investigator_affiliation>
    <investigator_full_name>Laura Vitiello, PhD</investigator_full_name>
    <investigator_title>Head of Cytofluorimeter unit</investigator_title>
  </responsible_party>
  <keyword>eosinophils</keyword>
  <keyword>immunophenotype</keyword>
  <keyword>inflammation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04494308
org study id: RP 06/18
nct id: NCT04494308
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a pilot non pharmacological observational study. Aim of the study is to analyze the
      immunophenotype of circulating eosinophils in chronic obstructive pulmonary disease (COPD)
      patients, and to correlate results with clinical status of patients (stable versus
      exacerbated patients, response to therapy). In about 30% of COPD patients there is an
      increase in the number of circulating eosinophils, which associates with an increased risk
      for exacerbation. However, no data is available on the role of eosinophils in this disease,
      on their activation status and their response to chemotactic factors. By multicolor flow
      cytometry the investigators will analyze membrane molecules and intracellular cytokines
      associated to chemotaxis, degranulation and inflammation. The study will enroll 30 patients
      (15 stable and 15 with exacerbation). Results will be analyzed taking into account clinical
      status,disease progression and response to treatment.
In about 30% of COPD patients there is an increased number of circulating eosinophils. On
      their membrane, eosinophils express several molecules, also related to their physiology,
      namely major histocompatibility complex (MHC) class II, needed for antigen presentation;
      CCR3, receptor for a variety of chemokines, including eotaxin (CCL11), eotaxin-3 (CCL26),
      monocyte chemotactict protein (MCP)-3 (CCL7), MCP-4 (CCL13), and RANTES (CCL5); cluster of
      differentiation (CD)125, which binds IL-5 and stimulates eosinophils proliferation; CD63, a
      marker that is upregulated after eosinophils degranulation; and CD294 (CRTH2) which is the
      prostaglandin D2 receptor, and is associated to allergy and inflammation . The hypothesis for
      the present trial is that different clinical phenotypes of COPD patients could be associated
      to different activation statuses of eosinophils, that can be evaluated analyzing by flow
      cytometry the membrane expression of the above mentioned molecules. In particular, the
      investigators hypothesize that membrane molecules may be modulated in different stages of the
      diseases, and may change after medical and rehabilitative therapies.

      The investigators will analyze phenotype of eosinophils from blood samples of patients with
      COPD, admitted to the hospital after an episode of exacerbation, or for routine controls. In
      this way, the association between a particular pattern of molecules expressed on eosinophils
      membrane and the severity of COPD will be defined. Moreover, for hospitalized patients,
      eosinophils phenotype also on discharge day will be analyzed. In this way the effect of
      therapies on eosinophils activation will be assessed. Clinical status of patients will be
      assessed by standard tests such as St George Respiratory Questionnaire (SGRQ), BODE index,
      COPD Assessment Test (CAT), Six min. Walking Test (6'WT), Pulmonary Function Tests (PFT).

      Eosinophils phenotype and in vitro cytokines production will be analyzed by multicolor flow
      cytometry. To minimize the effect of manipulation, staining of membrane molecules will be
      performed on whole blood samples, followed by lysis of erythrocytes. The following molecules
      will be analyzed: CD45, CD16, CD15, CD63, CCR3, CD125, CD294, Siglec-8. After in vitro
      stimulation with lipopolysaccharide (LPS) or CCL11, the production of interleukine (IL)-4,
      TGFbeta and IL-2 will be analyzed.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Association of eosinophils phenotype with clinical status in COPD patients
time frame: one year
description: We expect to identify different patterns of expression of molecules on eosinophils membrane that are associated with different clinical phenotypes of COPD patients. We will also associate eosinophils phenotype to the response to medical and rehabilitation therapy. The definition of these patterns will provide a diagnostic tool to rapidly identify patients that will benefit from a specific therapy
arm group label: exacerbated
description: COPD patients admitted to the hospital for an exacerbation occurred within the past 10 days.
arm group label: stable
description: COPD stable patients with no exacerbations in the past 3 months
intervention type: Other
intervention name: biomarker identification
description: flow cytometric analysis of eosinophils membrane molecules
arm group label: exacerbated
arm group label: stable
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Laura Vitiello, PhD
role: Principal Investigator
affiliation: IRCCS San Raffaele Pisana, Roma
last name: Vittorio Cardaci, MD
phone: +39 0666052336
email: vittorio.cardaci@sanraffaele.it
last name: Laura Vitiello, PhD
phone: +39 0652253440
email: laura.vitiello@sanraffaele.it
facility: 
status: Recruiting
contact: 
contact backup: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: IRCCS San Raffaele
investigator full name: Laura Vitiello, PhD
investigator title: Head of Cytofluorimeter unit
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: No