<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/NCT03303898</url>
  </required_header>
  <id_info>
    <org_study_id>17-AOI-04</org_study_id>
    <nct_id>NCT03303898</nct_id>
  </id_info>
  <brief_title>ASYMPTOMATIC CARRIER OF LEISHMANIA INFANTUM, MEDISERRANEAN VISCERAL LEISHMANIOSIS AGENT: STUDY OF IMMUNE RESPONSE -</brief_title>
  <acronym>Asymptoleish</acronym>
  <official_title>ASYMPTOMATIC CARRIER OF LEISHMANIA INFANTUM, MEDISERRANEAN VISCERAL LEISHMANIOSIS AGENT: STUDY OF IMMUNE RESPONSE - POSTULATE PRIOR TO HUMAN VACCINAL TRIALS Immune Response of Asymptomatic Carriers to L. Infantum</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire de Nice</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier Universitaire de Nice</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>
      Leishmaniasis is considered by the WHO as emerging and uncontrolled diseases. They are the&#xD;
      second leading cause of death and the fourth leading cause of morbidity in tropical diseases.&#xD;
      Leishmaniasis is parasitic reticulo-endotheliosis, the pathogenic agent of which is a&#xD;
      flagellated protozoan belonging to the genus Leishmania. It is estimated that there are about&#xD;
      2 million new cases per year. Effective treatments against visceral leishmaniasis are few and&#xD;
      resistance problems appear. To date, only a canine vaccine is available protecting dogs from&#xD;
      the development of canine leishmaniasis to L. infantum. In man, in parallel clinical cases,&#xD;
      leishmaniasis is characterized by a large number of asymptomatic carriers. This is the case&#xD;
      in the Alpes-Maritimes where 50% of the inhabitants of the hinterland of Nice are carriers of&#xD;
      the parasite.&#xD;
&#xD;
      the investigators wish to study the protective immune response to the parasite and more&#xD;
      particularly to the asymptomatic carriers. Indeed, these patients were infected with the&#xD;
      parasite and did not develop the disease. Understanding the protective immune response in&#xD;
      these patients against the parasite is therefore paramount in the development of a human&#xD;
      leishmaniasis vaccine.&#xD;
&#xD;
      For this purpose, the investigator wants to make an ex vivo study of the immune response of&#xD;
      lymphocytes coming from asymptomatic carriers after stimulation by Leishmania vaccine&#xD;
      peptides. It also wants to describe the immune response, after stimulation by these peptides,&#xD;
      in the lymphocytes of subjects asymptomatic carriers and lymphocytes from subjects not&#xD;
      infected with the parasite and comparing them. This study is unicentric and non-randomized.&#xD;
      It wishes to recruit 20 asymptomatic carriers of L. Infantum and 10 uninfected subjects. They&#xD;
      will be selected from our database. A simple blood sample will be taken. After verification&#xD;
      by quantitative PCR and western blotting of their status towards leishmaniasis, the team will&#xD;
      divide them into two groups (asymptomatic or healthy). Then the blood samples will be sent to&#xD;
      the team of Jean Loup Lemesre of the Laboratory INTERTRYP - UMR177 of the IRD in Montpellier.&#xD;
      ELISPOT analysis and assay of cytokines and proteases to describe the immune response of the&#xD;
      two groups and to compare them. In addition, cell typing will be performed by flow cytometry&#xD;
      to determine the type of lymphocytes involved in the immune response against Leishmania&#xD;
      peptides. HLA typing will also be performed to validate the HLA coverage of the peptides&#xD;
      tested. Finally, an analysis of the transcryptome will be carried out, which will allow to&#xD;
      identify the differential expression of genes and metabolic pathways involved in the immune&#xD;
      response and thus to understand how asymptomatic people can control the infection.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 10, 2017</start_date>
  <completion_date type="Actual">September 1, 2021</completion_date>
  <primary_completion_date type="Actual">November 10, 2017</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>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>immune response of lymphocytes from asymptomatic carriers</measure>
    <time_frame>15 months</time_frame>
    <description>decription of immune response of lymphocytes from asymptomatic carriers after stimulation by Leishmania vaccine peptides in ex vivo ELIPSPOT: Presence or absence of immune response.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Leishmaniasis, Cutaneous</condition>
  <arm_group>
    <arm_group_label>asymptomatic carriers</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>uninfected patient</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood sampling</intervention_name>
    <description>sampling of 7 blood tubes</description>
    <arm_group_label>asymptomatic carriers</arm_group_label>
    <arm_group_label>uninfected patient</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria for asymptomatic careers&#xD;
&#xD;
          -  Male and Female&#xD;
&#xD;
          -  Age between 18 and 80 years&#xD;
&#xD;
          -  PCR and western blot positive to L. Infantum (these exams will be redone as part of&#xD;
             the study).&#xD;
&#xD;
          -  Signature of informed consent&#xD;
&#xD;
          -  Affiliation to a social security scheme&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of known immunosuppression or immunosuppressive therapy. -HIV-positive people&#xD;
             will be excluded because of the immunosuppressive action of HIV on the immune system.&#xD;
             HIV status will be determined by interrogation.&#xD;
&#xD;
          -  Pregnant women will be excluded. A urinary pregnancy test (taken from the inclusion&#xD;
             proposal) will be performed for women of child-bearing age. The results will be&#xD;
             communicated to the patient by a doctor of her choice.&#xD;
&#xD;
          -  Persons under guardianship&#xD;
&#xD;
        Inclusion Criteria for healthy patient&#xD;
&#xD;
          -  Male or Female&#xD;
&#xD;
          -  Age between 18 and 80 years&#xD;
&#xD;
          -  PCR and western blot negative Leishmania (these exams will be redone as part of the&#xD;
             study).&#xD;
&#xD;
          -  Signature of informed consent&#xD;
&#xD;
          -  Affiliation to a social security scheme&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of known immunosuppression or immunosuppressive therapy. -HIV-positive people&#xD;
             will be excluded because of the immunosuppressive action of HIV on the immune system.&#xD;
             HIV status will be determined by interrogation.&#xD;
&#xD;
          -  Pregnant women will be excluded. A urinary pregnancy test (taken from the inclusion&#xD;
             proposal) will be performed for women of child-bearing age. The results will be&#xD;
             communicated to the patient by a doctor of her choice.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Nice Hospital</name>
      <address>
        <city>Nice</city>
        <zip>06000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>October 3, 2017</study_first_submitted>
  <study_first_submitted_qc>October 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <last_update_submitted>March 17, 2022</last_update_submitted>
  <last_update_submitted_qc>March 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 18, 2022</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>Leishmaniasis</mesh_term>
    <mesh_term>Leishmaniasis, Visceral</mesh_term>
    <mesh_term>Leishmaniasis, Cutaneous</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/NCT03303898
org study id: 17-AOI-04
nct id: NCT03303898
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Leishmaniasis is considered by the WHO as emerging and uncontrolled diseases. They are the
      second leading cause of death and the fourth leading cause of morbidity in tropical diseases.
      Leishmaniasis is parasitic reticulo-endotheliosis, the pathogenic agent of which is a
      flagellated protozoan belonging to the genus Leishmania. It is estimated that there are about
      2 million new cases per year. Effective treatments against visceral leishmaniasis are few and
      resistance problems appear. To date, only a canine vaccine is available protecting dogs from
      the development of canine leishmaniasis to L. infantum. In man, in parallel clinical cases,
      leishmaniasis is characterized by a large number of asymptomatic carriers. This is the case
      in the Alpes-Maritimes where 50% of the inhabitants of the hinterland of Nice are carriers of
      the parasite.

      the investigators wish to study the protective immune response to the parasite and more
      particularly to the asymptomatic carriers. Indeed, these patients were infected with the
      parasite and did not develop the disease. Understanding the protective immune response in
      these patients against the parasite is therefore paramount in the development of a human
      leishmaniasis vaccine.

      For this purpose, the investigator wants to make an ex vivo study of the immune response of
      lymphocytes coming from asymptomatic carriers after stimulation by Leishmania vaccine
      peptides. It also wants to describe the immune response, after stimulation by these peptides,
      in the lymphocytes of subjects asymptomatic carriers and lymphocytes from subjects not
      infected with the parasite and comparing them. This study is unicentric and non-randomized.
      It wishes to recruit 20 asymptomatic carriers of L. Infantum and 10 uninfected subjects. They
      will be selected from our database. A simple blood sample will be taken. After verification
      by quantitative PCR and western blotting of their status towards leishmaniasis, the team will
      divide them into two groups (asymptomatic or healthy). Then the blood samples will be sent to
      the team of Jean Loup Lemesre of the Laboratory INTERTRYP - UMR177 of the IRD in Montpellier.
      ELISPOT analysis and assay of cytokines and proteases to describe the immune response of the
      two groups and to compare them. In addition, cell typing will be performed by flow cytometry
      to determine the type of lymphocytes involved in the immune response against Leishmania
      peptides. HLA typing will also be performed to validate the HLA coverage of the peptides
      tested. Finally, an analysis of the transcryptome will be carried out, which will allow to
      identify the differential expression of genes and metabolic pathways involved in the immune
      response and thus to understand how asymptomatic people can control the infection.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: immune response of lymphocytes from asymptomatic carriers
time frame: 15 months
description: decription of immune response of lymphocytes from asymptomatic carriers after stimulation by Leishmania vaccine peptides in ex vivo ELIPSPOT: Presence or absence of immune response.
arm group label: asymptomatic carriers
arm group type: Other
arm group label: uninfected patient
arm group type: Other
intervention type: Procedure
intervention name: Blood sampling
description: sampling of 7 blood tubes
arm group label: asymptomatic carriers
arm group label: uninfected patient
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: France
responsible party type: Sponsor
mesh term: Leishmaniasis
mesh term: Leishmaniasis, Visceral
mesh term: Leishmaniasis, Cutaneous