<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/NCT03297203</url>
  </required_header>
  <id_info>
    <org_study_id>2017-24</org_study_id>
    <nct_id>NCT03297203</nct_id>
  </id_info>
  <brief_title>Innate Lymphoid Cells in Septic Shock</brief_title>
  <acronym>CriSIs</acronym>
  <official_title>Role of Innate Lymphoid Cells in the Immunosuppression of Septic Shock</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique Hopitaux De Marseille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique Hopitaux De Marseille</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>
      Less than ten years after their intial description, the comprehension of Innate Lymphoid&#xD;
      Cells (ILCs) biology is rapidly improving. They can be classified into four subgroups (ILCs&#xD;
      1, 2, 3 and NK cells) on the basis of their cytokine production and transcription factor&#xD;
      expression.&#xD;
&#xD;
      They seem to be players in infectious diseases in animals but their role in human&#xD;
      anti-bacterial defense remains unknown.&#xD;
&#xD;
      In this prospective work, the investigators will compare ILCs phenotyping in ICU patients&#xD;
      managed for a septic shock, comparing them to ICU patients without any infectious disease on&#xD;
      their inclusion. The investigators will also make a large immune mapping in all patients, to&#xD;
      place ILCs in the global immune depressed state observed in septic patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Septic shock is a major public health problem. Even if mortality is decreasing, it's still&#xD;
      high. Sepsis is a heterogeneous syndrome that encompasses a gamut of immune responses&#xD;
      occurring during the host's response to a serious, life-threatening infection. The immune&#xD;
      phenotype in sepsis ranges from proinflammatory (systemic inflammatory response syndrome and&#xD;
      cytokine storm syndrome) to anti-inflammatory (immune depressed state). In order to apprehend&#xD;
      septic shock as a whole, investigators should made a whole immune mapping in each patient.&#xD;
      Within immune mapping of septic shock patients, innate lymphoid cells (ILCs) have never been&#xD;
      explored.&#xD;
&#xD;
      ILCs include natural killer (NK) cells and three other main subsets, ILC1, ILC2 and ILC3,&#xD;
      referred as to 'helper-like ILCs'. Since their discovery, ILCs have been shown to contribute&#xD;
      to wound healing and defense against infection, and studies have revealed critical aspects of&#xD;
      their differentiation. They are studied by flow cytometry and much of the role of ILCs&#xD;
      remains to be elucidated, especially in humans. Like T Helper cells, investigators think it&#xD;
      could exist an imbalance of ILCs in the late course of septic shock which could participate&#xD;
      to the immune depressed state and the increase of patients' mortality at this stage.&#xD;
&#xD;
      So, investigators want to realize a whole immune mapping in patients managed for a septic&#xD;
      shock focusing particularly on the innate lymphoid cells. investigators think that ILC1s and&#xD;
      ILC3s could be increased in the patients' blood in the early course of the disease and could&#xD;
      participate to the cytokine storm syndrome. On the contrary, ILC2s could be increased in the&#xD;
      late stage of the septic shock, in correlation with the immune suppressed state.&#xD;
      investigators will compare the blood rates of ILCs in septic shock with the blood rates of&#xD;
      ILCs in patients with a bacterial sepsis but without severity criteria.&#xD;
&#xD;
      investigators will include 30 patients in septic shock (group 1) in the medical intensive&#xD;
      care unit of the Timone Hospital (RUM - Pr Gainnier) and 30 patients with a bacterial sepsis&#xD;
      alone, during a 6 months period. investigatorswill take two kits of blood samples for the&#xD;
      group 1, one during the early stage of the septic shock (48 first hours of care) and one&#xD;
      during the late stage of the disease (between the fourth and the sixth day). investigators'll&#xD;
      take only one kit of blood samples for the group 2. One kit includes one EDTA tube (5 mL) and&#xD;
      five Lithium Heparin tubes (25 mL). The immune mapping will be made by Julien Carvelli, a&#xD;
      gold medalist resident, in the framework of a Master 2. The analyses will be made in the&#xD;
      laboratory of immunology in the Conception Hospital (Pr Vivier's team).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2, 2017</start_date>
  <completion_date type="Actual">August 9, 2023</completion_date>
  <primary_completion_date type="Actual">August 31, 2019</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Secondary infections</measure>
    <time_frame>7 days</time_frame>
    <description>Any secondary infection diagnosed in ICU</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Septic Shock</condition>
  <arm_group>
    <arm_group_label>groupe1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients in septic shock (group 1) in the medical intensive care unit of the Timone Hospital.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>groupe 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patients with a bacterial sepsis alone, during a 6 months period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Blood sample</intervention_name>
    <description>The investigators will take two kits of blood samples for the group 1, one during the early stage of the septic shock (48 first hours of care) and one during the late stage of the disease (between the fourth and the sixth day). We'll take only one kit of blood samples for the group 2. One kit includes one EDTA tube (5 mL) and five Lithium Heparin tubes (25 mL). The immune mapping will be made by Julien Carvelli, a gold medalist resident, in the framework of a Master 2. The analyses will be made in the laboratory of immunology in the Conception Hospital (Pr Vivier's team).</description>
    <arm_group_label>groupe 2</arm_group_label>
    <arm_group_label>groupe1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Major patient&#xD;
&#xD;
          -  patient admitted to resuscitation for septic shock&#xD;
&#xD;
          -  patient admitted to intensive care for a serious condition and with no progressive&#xD;
             infection at the time of collection&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Minor patient&#xD;
&#xD;
          -  Patient with therepeutic limitations&#xD;
&#xD;
          -  Bone marrow failure&#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>Arnaud VANNESTE</last_name>
    <role>Study Director</role>
    <affiliation>Assistance Publisque Hôpitaux de Marseille</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital de la Timone Assistance Publique Hôpitaux de Marseille</name>
      <address>
        <city>Marseille</city>
        <zip>13354</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>September 26, 2017</study_first_submitted>
  <study_first_submitted_qc>September 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>August 9, 2023</last_update_submitted>
  <last_update_submitted_qc>August 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 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>Shock, Septic</mesh_term>
    <mesh_term>Shock</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/NCT03297203
org study id: 2017-24
nct id: NCT03297203
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Less than ten years after their intial description, the comprehension of Innate Lymphoid
      Cells (ILCs) biology is rapidly improving. They can be classified into four subgroups (ILCs
      1, 2, 3 and NK cells) on the basis of their cytokine production and transcription factor
      expression.

      They seem to be players in infectious diseases in animals but their role in human
      anti-bacterial defense remains unknown.

      In this prospective work, the investigators will compare ILCs phenotyping in ICU patients
      managed for a septic shock, comparing them to ICU patients without any infectious disease on
      their inclusion. The investigators will also make a large immune mapping in all patients, to
      place ILCs in the global immune depressed state observed in septic patients.
Septic shock is a major public health problem. Even if mortality is decreasing, it's still
      high. Sepsis is a heterogeneous syndrome that encompasses a gamut of immune responses
      occurring during the host's response to a serious, life-threatening infection. The immune
      phenotype in sepsis ranges from proinflammatory (systemic inflammatory response syndrome and
      cytokine storm syndrome) to anti-inflammatory (immune depressed state). In order to apprehend
      septic shock as a whole, investigators should made a whole immune mapping in each patient.
      Within immune mapping of septic shock patients, innate lymphoid cells (ILCs) have never been
      explored.

      ILCs include natural killer (NK) cells and three other main subsets, ILC1, ILC2 and ILC3,
      referred as to 'helper-like ILCs'. Since their discovery, ILCs have been shown to contribute
      to wound healing and defense against infection, and studies have revealed critical aspects of
      their differentiation. They are studied by flow cytometry and much of the role of ILCs
      remains to be elucidated, especially in humans. Like T Helper cells, investigators think it
      could exist an imbalance of ILCs in the late course of septic shock which could participate
      to the immune depressed state and the increase of patients' mortality at this stage.

      So, investigators want to realize a whole immune mapping in patients managed for a septic
      shock focusing particularly on the innate lymphoid cells. investigators think that ILC1s and
      ILC3s could be increased in the patients' blood in the early course of the disease and could
      participate to the cytokine storm syndrome. On the contrary, ILC2s could be increased in the
      late stage of the septic shock, in correlation with the immune suppressed state.
      investigators will compare the blood rates of ILCs in septic shock with the blood rates of
      ILCs in patients with a bacterial sepsis but without severity criteria.

      investigators will include 30 patients in septic shock (group 1) in the medical intensive
      care unit of the Timone Hospital (RUM - Pr Gainnier) and 30 patients with a bacterial sepsis
      alone, during a 6 months period. investigatorswill take two kits of blood samples for the
      group 1, one during the early stage of the septic shock (48 first hours of care) and one
      during the late stage of the disease (between the fourth and the sixth day). investigators'll
      take only one kit of blood samples for the group 2. One kit includes one EDTA tube (5 mL) and
      five Lithium Heparin tubes (25 mL). The immune mapping will be made by Julien Carvelli, a
      gold medalist resident, in the framework of a Master 2. The analyses will be made in the
      laboratory of immunology in the Conception Hospital (Pr Vivier's team).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Secondary infections
time frame: 7 days
description: Any secondary infection diagnosed in ICU
arm group label: groupe1
arm group type: Experimental
description: patients in septic shock (group 1) in the medical intensive care unit of the Timone Hospital.
arm group label: groupe 2
arm group type: Active Comparator
description: patients with a bacterial sepsis alone, during a 6 months period.
intervention type: Behavioral
intervention name: Blood sample
description: The investigators will take two kits of blood samples for the group 1, one during the early stage of the septic shock (48 first hours of care) and one during the late stage of the disease (between the fourth and the sixth day). We'll take only one kit of blood samples for the group 2. One kit includes one EDTA tube (5 mL) and five Lithium Heparin tubes (25 mL). The immune mapping will be made by Julien Carvelli, a gold medalist resident, in the framework of a Master 2. The analyses will be made in the laboratory of immunology in the Conception Hospital (Pr Vivier's team).
arm group label: groupe 2
arm group label: groupe1
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Arnaud VANNESTE
role: Study Director
affiliation: Assistance Publisque Hôpitaux de Marseille
facility: 
country: France
responsible party type: Sponsor
mesh term: Shock, Septic
mesh term: Shock