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/NCT06021743</url>
    </required_header>
    <id_info>
      <org_study_id>UHID-08</org_study_id>
      <nct_id>NCT06021743</nct_id>
    </id_info>
    <brief_title>The Role of Immune Semaphorins in Steatotic Liver Disease and Sepsis</brief_title>
    <acronym>SepsisFAT</acronym>
    <official_title>The Role of Immune Semaphorins in Steatotic Liver Disease and Sepsis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital for Infectious Diseases, Croatia</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Croatian Science Foundation</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University Hospital for Infectious Diseases, Croatia</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>
        The impact of the complex liver immunological network on sepsis outcome is largely unknown.&#xD;
        Steatotic liver disease (SLD) is the most common chronic liver disease with prevalence of 25%&#xD;
        in European countries. The question remains whether patients with SLD are more prone to&#xD;
        bacterial infections and what is the impact of persistent liver inflammation to the systemic&#xD;
        response to infection, sepsis course and outcomes. Semaphorins are a large family of secreted&#xD;
        and membrane-bound biological response modifiers present in many organ systems that are&#xD;
        associated with SLD and development of fibrosis, but also might regulate systemic immune&#xD;
        responses in sepsis. This study will investigate the association of semaphorins with sepsis&#xD;
        outcomes in patients with SLD.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The liver, with its ability to produce acute phase proteins, complement and cytokines, plays&#xD;
        a central role in regulating inflammation. A balanced pro- and anti-inflammatory liver&#xD;
        response results in bacterial clearance and resolution of inflammation. Steatotic liver&#xD;
        disease (SLD) is the most common chronic liver disease associated with systemic changes in&#xD;
        immune response. Although there are numerous immunological links between sepsis and SLD,&#xD;
        there is a significant gap in knowledge regarding the role of SLD in sepsis. Semaphorins were&#xD;
        recently recognized as one of the key regulators of immune responses; while some suppress&#xD;
        immune cells activation, proliferation and production of inflammatory cytokines, others&#xD;
        stimulate immune responses. Semaphorins were recently shown to be associated with&#xD;
        pathogenesis of viral hepatitis, SLD and progression of fibrosis. However, their role in&#xD;
        sepsis is unknown. The hypothesis of this project is that semaphorins are regulators of&#xD;
        inflammation in patients with SLD that have impact on sepsis outcome.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">January 1, 2022</start_date>
    <completion_date type="Anticipated">March 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">February 28, 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>Detection of semaphorins in patients with sepsis and SLD</measure>
      <time_frame>24 months</time_frame>
      <description>Measurement of semaphorins concentration in serum of patients with SLD and sepsis by enzyme-linked immunosorbent assay (ELISA)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Impact of SLD on sepsis outcomes</measure>
      <time_frame>24 months</time_frame>
      <description>Analysis of the impact of SLD and steatosis grade (grade 1 - mild steatosis, 2 - moderate, 3 - severe steatosis) on sepsis complications and outcomes.</description>
    </primary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">160</enrollment>
    <condition>Steatosis of Liver</condition>
    <condition>Sepsis</condition>
    <condition>Immune Response</condition>
    <arm_group>
      <arm_group_label>Sepsis</arm_group_label>
      <description>Patients hospitalized due to the sepsis</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Evaluation of the degree of steatosis</intervention_name>
      <description>The degree of steatosis will be estimated using the ultrasound and a method for grading steatosis will be measuring the degree of ultrasound attenuation by hepatic fat using a process based on simultaneous transient elastography (TE) which measures the degree of steatosis.</description>
      <arm_group_label>Sepsis</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Screening for the components of metabolic syndrome</intervention_name>
      <description>Anthropometric measures including height, weight, waist circumference and hip circumference will be measured in all patients. Results of the routine laboratory tests as part of the standard diagnostic procedure will be collected: CRP, leukocyte count, ratio neutrophils and lymphocytes, hemoglobin, platelet count, urea, creatinine, bilirubin, AST, ALT, GGT, ALP, albumins, fasting glucose.</description>
      <arm_group_label>Sepsis</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Measurement of serum semaphorin concentrations</intervention_name>
      <description>Semaphorin concentration will be measured in patient sera by ELISA.</description>
      <arm_group_label>Sepsis</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Measurement of inflammatory cytokines</intervention_name>
      <description>A panel of pro- and anti-inflammatory markers will be determined by flow cytometer microsphere-based assay.</description>
      <arm_group_label>Sepsis</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          All adult patients admitted at three clinical departments at UHID that meet inclusion&#xD;
          criteria will be offered to participate in the study during a 24-month period.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  2 or more SIRS (Systemic Inflammatory Response Syndrome) criteria (1. Hyperthermia&#xD;
               &gt;38.3°C or Hypothermia &lt;36°C; 2. Tachycardia &gt;90 bpm; 3. Tachypnea &gt;20 bpm; 3.&#xD;
               Leukocytosis (&gt;12,000 μL-1) or Leukopenia (&lt;4,000 μL-1))&#xD;
  &#xD;
            -  clinical suspicion of sepsis&#xD;
  &#xD;
            -  enrolled within 24 hours of hospital admission&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  no consent&#xD;
  &#xD;
            -  immunosuppression&#xD;
  &#xD;
            -  malignancies&#xD;
  &#xD;
            -  immune diseases&#xD;
  &#xD;
            -  pregnancy&#xD;
  &#xD;
            -  HIV infection&#xD;
  &#xD;
            -  presence of chronic liver disease&#xD;
  &#xD;
            -  consumption of alcohol &gt; 20 g/day&#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>Neven Papic, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>School of Medicine, University of Zagreb</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Nina Vrsaljko, MD</last_name>
      <phone>+385914012018</phone>
      <email>nvrsaljko@bfm.hr</email>
    </overall_contact>
    <location>
      <facility>
        <name>University Hospital for Infectious Diseases Zagreb</name>
        <address>
          <city>Zagreb</city>
          <zip>10000</zip>
          <country>Croatia</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Neven Papic, MD, PhD</last_name>
        <phone>+38512826222</phone>
        <email>npapic@bfm.hr</email>
      </contact>
      <investigator>
        <last_name>Neven Papic, MD, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Branimir Gjurasin, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Juraj Krznaric, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Nina Vrsaljko, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Lara Samadan</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Croatia</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 27, 2023</study_first_submitted>
    <study_first_submitted_qc>August 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 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>Sepsis</mesh_term>
      <mesh_term>Toxemia</mesh_term>
      <mesh_term>Liver Diseases</mesh_term>
      <mesh_term>Fatty Liver</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/NCT06021743
  org study id: UHID-08
  nct id: NCT06021743
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The impact of the complex liver immunological network on sepsis outcome is largely unknown.
        Steatotic liver disease (SLD) is the most common chronic liver disease with prevalence of 25%
        in European countries. The question remains whether patients with SLD are more prone to
        bacterial infections and what is the impact of persistent liver inflammation to the systemic
        response to infection, sepsis course and outcomes. Semaphorins are a large family of secreted
        and membrane-bound biological response modifiers present in many organ systems that are
        associated with SLD and development of fibrosis, but also might regulate systemic immune
        responses in sepsis. This study will investigate the association of semaphorins with sepsis
        outcomes in patients with SLD.
  The liver, with its ability to produce acute phase proteins, complement and cytokines, plays
        a central role in regulating inflammation. A balanced pro- and anti-inflammatory liver
        response results in bacterial clearance and resolution of inflammation. Steatotic liver
        disease (SLD) is the most common chronic liver disease associated with systemic changes in
        immune response. Although there are numerous immunological links between sepsis and SLD,
        there is a significant gap in knowledge regarding the role of SLD in sepsis. Semaphorins were
        recently recognized as one of the key regulators of immune responses; while some suppress
        immune cells activation, proliferation and production of inflammatory cytokines, others
        stimulate immune responses. Semaphorins were recently shown to be associated with
        pathogenesis of viral hepatitis, SLD and progression of fibrosis. However, their role in
        sepsis is unknown. The hypothesis of this project is that semaphorins are regulators of
        inflammation in patients with SLD that have impact on sepsis outcome.
  observational model: Cohort
  time perspective: Prospective
  measure: Detection of semaphorins in patients with sepsis and SLD
  time frame: 24 months
  description: Measurement of semaphorins concentration in serum of patients with SLD and sepsis by enzyme-linked immunosorbent assay (ELISA)
  measure: Impact of SLD on sepsis outcomes
  time frame: 24 months
  description: Analysis of the impact of SLD and steatosis grade (grade 1 - mild steatosis, 2 - moderate, 3 - severe steatosis) on sepsis complications and outcomes.
  arm group label: Sepsis
  description: Patients hospitalized due to the sepsis
  intervention type: Diagnostic Test
  intervention name: Evaluation of the degree of steatosis
  description: The degree of steatosis will be estimated using the ultrasound and a method for grading steatosis will be measuring the degree of ultrasound attenuation by hepatic fat using a process based on simultaneous transient elastography (TE) which measures the degree of steatosis.
  arm group label: Sepsis
  intervention type: Diagnostic Test
  intervention name: Screening for the components of metabolic syndrome
  description: Anthropometric measures including height, weight, waist circumference and hip circumference will be measured in all patients. Results of the routine laboratory tests as part of the standard diagnostic procedure will be collected: CRP, leukocyte count, ratio neutrophils and lymphocytes, hemoglobin, platelet count, urea, creatinine, bilirubin, AST, ALT, GGT, ALP, albumins, fasting glucose.
  arm group label: Sepsis
  intervention type: Diagnostic Test
  intervention name: Measurement of serum semaphorin concentrations
  description: Semaphorin concentration will be measured in patient sera by ELISA.
  arm group label: Sepsis
  intervention type: Diagnostic Test
  intervention name: Measurement of inflammatory cytokines
  description: A panel of pro- and anti-inflammatory markers will be determined by flow cytometer microsphere-based assay.
  arm group label: Sepsis
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Neven Papic, MD, PhD
  role: Principal Investigator
  affiliation: School of Medicine, University of Zagreb
  last name: Nina Vrsaljko, MD
  phone: +385914012018
  email: nvrsaljko@bfm.hr
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  country: Croatia
  responsible party type: Sponsor
  mesh term: Sepsis
  mesh term: Toxemia
  mesh term: Liver Diseases
  mesh term: Fatty Liver
  sharing ipd: No