<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/NCT03837730</url>
  </required_header>
  <id_info>
    <org_study_id>P/2018/353</org_study_id>
    <nct_id>NCT03837730</nct_id>
  </id_info>
  <brief_title>Citrulline and Arginase Activity in Severe Sepsis and Septic Shock</brief_title>
  <acronym>CARS</acronym>
  <official_title>Activity and Expression of Plasma Arginase in Patients With Severe Sepsis or Septic Shock as Prognostic Value</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire de Besancon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier Universitaire de Besancon</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>
      Sepsis is an acute pathology defined as an inappropriate response of the host to infection,&#xD;
      resulting in the onset of organ failure (Quick SOFA ≥2, or SOFA ≥2). Septic shock is a sepsis&#xD;
      associated with an elevation of lactate ≥ 2 mmol / l and an arterial hypotension requiring&#xD;
      vasoactive drugs. Several studies highlighted that sepsis is associated with a plasma&#xD;
      L-arginine deficiency. This deficiency induces a lower availability of L-arginine for&#xD;
      multiple metabolic pathways including those involved in the synthesis of nitric oxide (NO) in&#xD;
      the vascular endothelium via NO synthase. NO is the main endogenous vasodilator mediator, a&#xD;
      lower synthesis induces a vascular and endothelial dysfunction that can promote the&#xD;
      occurrence of an organic dysfunction during sepsis. Decrease in available NO was confirmed in&#xD;
      patients with sepsis and appears correlated with severity.&#xD;
&#xD;
      L-arginine deficiency can have multiple origins:&#xD;
&#xD;
        -  L-arginine deficiency resulting from a decrease in endogenous production from citrulline&#xD;
           synthesized by the enterocytes. Such enterocyte dysfunction has been confirmed in&#xD;
           patients with sepsis and is characterized biologically by elevated plasma levels of&#xD;
           I-FABP (intestinal fatty acid binding protein - enterocyte-specific protein, cytolysis&#xD;
           marker) and lower than that of citrulline (hypocitrullinemia, marker of lower activity).&#xD;
&#xD;
        -  L-arginine deficiency may also result from a catabolism increase via arginase activity&#xD;
           increased. This ubiquitous enzyme, having 2 isoforms (Arg1 and Arg2), allows the&#xD;
           synthesis of urea and ornithine from L-arginine. An increase in arginase activity would&#xD;
           decrease the available reserves of L-arginine for NO synthesis.&#xD;
&#xD;
      The objectives of this work is to evaluate, in patients with severe sepsis or septic shock,&#xD;
      the prognostic value of the plasma arginase activity and the plasma expression of 2 isoforms&#xD;
      Arg1 and Arg2, their kinetics, and the link between activity / expression of arginase and&#xD;
      enterocyte dysfunction.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">February 10, 2019</start_date>
  <completion_date type="Anticipated">August 10, 2019</completion_date>
  <primary_completion_date type="Anticipated">May 10, 2019</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>prognostic value of plasma arginase activity and expression at ICU admission in patients with severe sepsis or septic shock</measure>
    <time_frame>28 days</time_frame>
    <description>activity / expression of plasma arginase at ICU admission and 28-day mortality rate from admission to intensive care</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>activity / expression kinetic of plasma arginase</measure>
    <time_frame>during the first 7 days of ICU admission</time_frame>
    <description>3 points kinetic : admission, day 3 and day 7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>prognostic value of enterocyte damage</measure>
    <time_frame>28 days</time_frame>
    <description>at ICU admission and 28-day mortality rate from admission to intensive care</description>
  </secondary_outcome>
  <enrollment type="Anticipated">118</enrollment>
  <condition>Intensive Care Units</condition>
  <condition>Infection</condition>
  <condition>Biomarkers</condition>
  <condition>Sepsis</condition>
  <condition>Septic Shock</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood sample at ICU admission, day 3 and day 7 biomarkers analysis: arginase activity,&#xD;
      citrulline and IFABP&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        patients admitted to the ICU for severe sepsis or septic shock&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years old or older&#xD;
&#xD;
          -  Patient admitted to ICU&#xD;
&#xD;
          -  Diagnosis, suspected or confirmed, of severe sepsis or septic shock&#xD;
&#xD;
          -  Expected ICU stay of at least 2 days&#xD;
&#xD;
          -  Affiliation to a social security system or recipient of a such system&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Chronic intestinal pathology&#xD;
&#xD;
          -  Chronic renal failure defined by creatinine clearance &lt;50 ml / min / 1.73m2 (CKD-EPI)&#xD;
&#xD;
          -  Severe hepatic insufficiency (Child-Pugh stage C score)&#xD;
&#xD;
          -  Legal incapacity or limited legal capacity&#xD;
&#xD;
          -  Subject unlikely to cooperate with the study and / or weak cooperation anticipated by&#xD;
             the investigator&#xD;
&#xD;
          -  Patient within the exclusion period of another study or planned by the &quot;national file&#xD;
             of volunteers&quot;&#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>Gaël PITON, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU de Besancon</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gaël PITON, MD</last_name>
    <phone>381668127</phone>
    <phone_ext>+33</phone_ext>
    <email>gpiton@chu-besancon.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lucie VETTORETTI</last_name>
    <phone>381218378</phone>
    <phone_ext>+33</phone_ext>
    <email>lvettoretti@chu-besancon.fr</email>
  </overall_contact_backup>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>February 8, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>February 8, 2019</last_update_submitted>
  <last_update_submitted_qc>February 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ICU, sepsis, septic shok, arginase, citrulline</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
    <mesh_term>Shock, Septic</mesh_term>
    <mesh_term>Shock</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03837730
org study id: P/2018/353
nct id: NCT03837730
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Sepsis is an acute pathology defined as an inappropriate response of the host to infection,
      resulting in the onset of organ failure (Quick SOFA ≥2, or SOFA ≥2). Septic shock is a sepsis
      associated with an elevation of lactate ≥ 2 mmol / l and an arterial hypotension requiring
      vasoactive drugs. Several studies highlighted that sepsis is associated with a plasma
      L-arginine deficiency. This deficiency induces a lower availability of L-arginine for
      multiple metabolic pathways including those involved in the synthesis of nitric oxide (NO) in
      the vascular endothelium via NO synthase. NO is the main endogenous vasodilator mediator, a
      lower synthesis induces a vascular and endothelial dysfunction that can promote the
      occurrence of an organic dysfunction during sepsis. Decrease in available NO was confirmed in
      patients with sepsis and appears correlated with severity.

      L-arginine deficiency can have multiple origins:

        -  L-arginine deficiency resulting from a decrease in endogenous production from citrulline
           synthesized by the enterocytes. Such enterocyte dysfunction has been confirmed in
           patients with sepsis and is characterized biologically by elevated plasma levels of
           I-FABP (intestinal fatty acid binding protein - enterocyte-specific protein, cytolysis
           marker) and lower than that of citrulline (hypocitrullinemia, marker of lower activity).

        -  L-arginine deficiency may also result from a catabolism increase via arginase activity
           increased. This ubiquitous enzyme, having 2 isoforms (Arg1 and Arg2), allows the
           synthesis of urea and ornithine from L-arginine. An increase in arginase activity would
           decrease the available reserves of L-arginine for NO synthesis.

      The objectives of this work is to evaluate, in patients with severe sepsis or septic shock,
      the prognostic value of the plasma arginase activity and the plasma expression of 2 isoforms
      Arg1 and Arg2, their kinetics, and the link between activity / expression of arginase and
      enterocyte dysfunction.
observational model: Cohort
time perspective: Prospective
measure: prognostic value of plasma arginase activity and expression at ICU admission in patients with severe sepsis or septic shock
time frame: 28 days
description: activity / expression of plasma arginase at ICU admission and 28-day mortality rate from admission to intensive care
measure: activity / expression kinetic of plasma arginase
time frame: during the first 7 days of ICU admission
description: 3 points kinetic : admission, day 3 and day 7
measure: prognostic value of enterocyte damage
time frame: 28 days
description: at ICU admission and 28-day mortality rate from admission to intensive care
blood sample at ICU admission, day 3 and day 7 biomarkers analysis: arginase activity,
      citrulline and IFABP
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gaël PITON, MD
role: Principal Investigator
affiliation: CHU de Besancon
last name: Gaël PITON, MD
phone: 381668127
phone ext: +33
email: gpiton@chu-besancon.fr
last name: Lucie VETTORETTI
phone: 381218378
phone ext: +33
email: lvettoretti@chu-besancon.fr
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Toxemia
mesh term: Shock, Septic
mesh term: Shock
sharing ipd: Undecided