<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/NCT03761875</url>
  </required_header>
  <id_info>
    <org_study_id>87RI18-0021</org_study_id>
    <nct_id>NCT03761875</nct_id>
  </id_info>
  <brief_title>NK Cell Deregulation in HBV Patients</brief_title>
  <acronym>LiNKeB</acronym>
  <official_title>NK Cell Deregulation in HBV Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Limoges</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Limoges</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>
      Natural Killer (NK) cells play a large role in the innate immune response as they are&#xD;
      equipped to kill infected or tumor cells. They express a panel of activating and inhibitory&#xD;
      receptors that regulate the destruction of the target cell. Many reports have shown that NK&#xD;
      cell function is suppressed in CHB patients. Exhaustion occurs when activating receptors&#xD;
      become over stimulated leading to the loss of NK function. The investigators hypothesize that&#xD;
      NK cells are rendered dysfunctional/ exhausted by HBV. The primary objective is to determined&#xD;
      the phenotypical modifications and mechanisms associated to NK cell dysfunction, during&#xD;
      different phases of CHB infection, in not treated patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Using a previous cohort from the Limoges Hospital, the investigators have identified by&#xD;
      multi-parametric flow cytometry phenotypic, cytokine and signaling molecules that are altered&#xD;
      in NK cells from CHB patients during the inactive phase. Phenotypic changes observed include&#xD;
      the downregulation of CD160, NKp30, CD16 and Tim-3. The expansion of 'adaptive' NK cells&#xD;
      (FCεRg- NKG2C+ or CD57hi), and the upregulation of CD107a (steady state), NKG2D and 41BB.&#xD;
      Functional changes include the decrease in the levels of IFNγ, TNFα and MIP1β. Cellular&#xD;
      metabolism is now recognized to regulate functional properties of immune cells such as T or&#xD;
      NK cells. The mammalian target of rapamycin (mTOR) kinase is a key regulator of cellular&#xD;
      metabolism, integrating environmental cues to control downstream metabolic pathways. mTOR is&#xD;
      the catalytic subunit of two different complexes: mTORC1 and mTORC2, the activity of which&#xD;
      can be measured by measuring the level of phosphorylation of the proteins S6 and Akt&#xD;
      respectively. The lab has previously shown that the mTOR pathway regulates NK cell&#xD;
      development and activation 2. The investigators have observed that pS6 and pAkt are also&#xD;
      decreased in CHB patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 11, 2018</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>Using a multiparameter flow cytometry approach, we will assess the mean fluorescence intensity (MFI) of the listed molecules expressed on Natural Killer cells</measure>
    <time_frame>At inclusion, day 0</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Hepatitis B Virus</condition>
  <arm_group>
    <arm_group_label>CHB patients</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>a blood sample is done during a follow-up visit</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>a blood sample</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>blood sample CHB patients</intervention_name>
    <description>During a boold sample at only one follow up visit:&#xD;
3 tubes EDTA 10 ml per patient&#xD;
1 tube &quot;Paxgene&quot; 1ml&#xD;
1 dry tube per patient</description>
    <arm_group_label>CHB patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>boold sample Control group</intervention_name>
    <description>2 tubes EDTA ideally age and sex matched to CHB patient.&#xD;
1 tube &quot;Paxgene&quot; 1ml&#xD;
1 dry tube</description>
    <arm_group_label>Control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients must meet all of the following inclusion criteria to be eligible for participation&#xD;
        in this study:&#xD;
&#xD;
          -  Male or female, age ≥18 years&#xD;
&#xD;
          -  HBV infection or chronic HBV infection&#xD;
&#xD;
          -  Willing and able to provide written informed consent&#xD;
&#xD;
        Healthy donors must meet all of the following inclusion criteria to be eligible for&#xD;
        participation in this study:&#xD;
&#xD;
          -  Male or female, age between 18 and 50 years&#xD;
&#xD;
          -  Willing and able to provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who meet any of the following exclusion criteria are not to be enrolled in&#xD;
             this study:&#xD;
&#xD;
          -  Infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Chronic liver disease of a non-HBV etiology&#xD;
&#xD;
          -  Immune or cancerous disease&#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_official>
    <last_name>Véronique LOUSTAUD-RATTI, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Limoges Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Uzma HASAN</last_name>
    <role>Study Director</role>
    <affiliation>Inserm U1111, Lyon</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Véronique LOUSTAUD-RATTI, MD</last_name>
    <phone>+33 5 55 05 66 84</phone>
    <email>veronique.loustaud-ratti@unilim.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sophie ALAIN, MD</last_name>
    <phone>05 55 05 67 28</phone>
    <email>sophie.alain@unilim.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Limoges Hospital</name>
      <address>
        <city>Limoges</city>
        <zip>87 042</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Véronique LOUSTAUD-RATTI, MD</last_name>
      <phone>+33 5 55 05 66 84</phone>
      <email>veronique.loustaud-ratti@unilim.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 12, 2018</study_first_submitted>
  <study_first_submitted_qc>November 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 3, 2018</study_first_posted>
  <last_update_submitted>May 4, 2023</last_update_submitted>
  <last_update_submitted_qc>May 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatitis B Virus - Natural Killer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis</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/NCT03761875
org study id: 87RI18-0021
nct id: NCT03761875
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Natural Killer (NK) cells play a large role in the innate immune response as they are
      equipped to kill infected or tumor cells. They express a panel of activating and inhibitory
      receptors that regulate the destruction of the target cell. Many reports have shown that NK
      cell function is suppressed in CHB patients. Exhaustion occurs when activating receptors
      become over stimulated leading to the loss of NK function. The investigators hypothesize that
      NK cells are rendered dysfunctional/ exhausted by HBV. The primary objective is to determined
      the phenotypical modifications and mechanisms associated to NK cell dysfunction, during
      different phases of CHB infection, in not treated patients.
Using a previous cohort from the Limoges Hospital, the investigators have identified by
      multi-parametric flow cytometry phenotypic, cytokine and signaling molecules that are altered
      in NK cells from CHB patients during the inactive phase. Phenotypic changes observed include
      the downregulation of CD160, NKp30, CD16 and Tim-3. The expansion of 'adaptive' NK cells
      (FCεRg- NKG2C+ or CD57hi), and the upregulation of CD107a (steady state), NKG2D and 41BB.
      Functional changes include the decrease in the levels of IFNγ, TNFα and MIP1β. Cellular
      metabolism is now recognized to regulate functional properties of immune cells such as T or
      NK cells. The mammalian target of rapamycin (mTOR) kinase is a key regulator of cellular
      metabolism, integrating environmental cues to control downstream metabolic pathways. mTOR is
      the catalytic subunit of two different complexes: mTORC1 and mTORC2, the activity of which
      can be measured by measuring the level of phosphorylation of the proteins S6 and Akt
      respectively. The lab has previously shown that the mTOR pathway regulates NK cell
      development and activation 2. The investigators have observed that pS6 and pAkt are also
      decreased in CHB patients.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Using a multiparameter flow cytometry approach, we will assess the mean fluorescence intensity (MFI) of the listed molecules expressed on Natural Killer cells
time frame: At inclusion, day 0
arm group label: CHB patients
arm group type: Other
description: a blood sample is done during a follow-up visit
arm group label: Control group
arm group type: Other
description: a blood sample
intervention type: Other
intervention name: blood sample CHB patients
description: During a boold sample at only one follow up visit:
3 tubes EDTA 10 ml per patient
1 tube "Paxgene" 1ml
1 dry tube per patient
arm group label: CHB patients
intervention type: Other
intervention name: boold sample Control group
description: 2 tubes EDTA ideally age and sex matched to CHB patient.
1 tube "Paxgene" 1ml
1 dry tube
arm group label: Control group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Véronique LOUSTAUD-RATTI, MD
role: Principal Investigator
affiliation: Limoges Hospital
last name: Uzma HASAN
role: Study Director
affiliation: Inserm U1111, Lyon
last name: Véronique LOUSTAUD-RATTI, MD
phone: +33 5 55 05 66 84
email: veronique.loustaud-ratti@unilim.fr
last name: Sophie ALAIN, MD
phone: 05 55 05 67 28
email: sophie.alain@unilim.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Hepatitis B
mesh term: Hepatitis