<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/NCT03013673</url>
  </required_header>
  <id_info>
    <org_study_id>ITM0915</org_study_id>
    <nct_id>NCT03013673</nct_id>
  </id_info>
  <brief_title>Predicting Visceral Leishmaniasis in HIV Infected Patients</brief_title>
  <acronym>PreLeisH</acronym>
  <official_title>Predicting Visceral Leishmaniasis in HIV Infected Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Tropical Medicine, Belgium</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Gondar, Gondar, Ethiopia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medecins Sans Frontieres, Netherlands</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bureau of Health, Abdurafi, Ethiopia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institute of Tropical Medicine, Belgium</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this cohort study, the investigators will study the asymptomatic period preceding the&#xD;
      onset of active Visceral Leishmaniasis (VL) in HIV-infected individuals from VL endemic&#xD;
      regions in Ethiopia as an avenue to develop an evidence-based screen and treat strategy to&#xD;
      prevent progression to active VL.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      HIV co-infection drastically increases the risk of developing active VL. Clinical outcomes&#xD;
      are dire in immune-compromised patients even with the best available treatment, and relapse&#xD;
      is frequent. The incubation period may provide an important window of opportunity for a&#xD;
      pre-emptive &quot;screen an treat&quot; approach in HIV co-infected patients to prevent progression&#xD;
      from infection to the active disease. However, no recommendations exist to date due to lack&#xD;
      of solid evidence.&#xD;
&#xD;
      It is not known which patients are at highest risk of disease progression, which role&#xD;
      parasite/host/HIV factors play in the asymptomatic infection phase, and what the diagnostic&#xD;
      values of existing Leishmania infection markers are. Such information is needed to develop a&#xD;
      prognostic clinical tool for the detection of HIV patients at high risk of developing active&#xD;
      VL.&#xD;
&#xD;
      Therefore, the aim is to study the asymptomatic period preceding the onset of active VL in&#xD;
      HIV-infected individuals from VL endemic regions in Ethiopia as an avenue to develop an&#xD;
      evidence-based screen and treat strategy to prevent progression to active VL. This will be a&#xD;
      prospective cohort study with one year of follow-up for patients who remain VL free. Patients&#xD;
      developing active VL during the study period will be followed until the end of the study&#xD;
      duration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to the ongoing conflict in the Tigray region&#xD;
  </why_stopped>
  <start_date type="Actual">October 11, 2017</start_date>
  <completion_date type="Actual">May 31, 2021</completion_date>
  <primary_completion_date type="Actual">May 31, 2021</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>Prevalence of asymptomatic Leishmania infection</measure>
    <time_frame>January 2018</time_frame>
    <description>The proportion of individuals with asymptomatic Leishmania infection at enrolment, among all enrolled participants</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence rate of asymptomatic Leishmania infection</measure>
    <time_frame>January 2020</time_frame>
    <description>The number of individuals with newly diagnosed asymptomatic Leishmania infection per person-years at risk during follow-up, among participants without Leishmania infection at enrolment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evolution of Leishmania infection markers</measure>
    <time_frame>January 2020</time_frame>
    <description>The proportions of individuals with positive test results for the different Leishmania infection markers at each follow-up visit</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence rate of active VL</measure>
    <time_frame>January 2020</time_frame>
    <description>The number of individuals who develop active VL per person-years at risk during follow-up, among all enrolled participants</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Risk factors for active VL</measure>
    <time_frame>January 2020</time_frame>
    <description>The association between the risk to develop active VL during follow-up and demographic/clinical characteristics as well as HIV/host immunity/Leishmania infection markers from baseline onwards</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Prognostic tool for active VL</measure>
    <time_frame>January 2021</time_frame>
    <description>A clinical decision algorithm, prioritizing and integrating identified risk factors, that is able to most efficiently predict the risk of developing active VL within 12 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patterns in host immune markers for asymptomatic Leishmania infection</measure>
    <time_frame>January 2020</time_frame>
    <description>The association between asymptomatic Leishmania infection and the levels of the different host immune markers, among participants tested for host immune markers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of host immune markers</measure>
    <time_frame>January 2020</time_frame>
    <description>The average levels of the different host immune markers at each follow-up visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patterns in host immune markers for VL treatment failure</measure>
    <time_frame>January 2021</time_frame>
    <description>The association between the risk of VL treatment failure and the levels and evolution of the different host immune markers, among participants who develop active VL and receive VL treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patterns in host immune markers for VL relapse</measure>
    <time_frame>January 2021</time_frame>
    <description>The association between the risk of VL relapse and the levels and evolution of the different host immune markers, among participants who develop active VL</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">566</enrollment>
  <condition>Leishmaniasis, Visceral</condition>
  <arm_group>
    <arm_group_label>HIV</arm_group_label>
    <description>HIV infected individuals residing in VL-endemic areas in Northern Ethiopia</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No intervention</intervention_name>
    <description>No intervention</description>
    <arm_group_label>HIV</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      All samples and sample left-overs (blood and urine) not used during the course of this study&#xD;
      will be stored for 25 years after the end of the study.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        HIV-infected individuals residing in VL-endemic areas in Northern Ethiopia&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed HIV-positive&#xD;
&#xD;
          -  Enrolled in HIV care at the study site&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age under 18 years&#xD;
&#xD;
          -  Diagnosis of active Visceral Leishmaniasis at enrolment&#xD;
&#xD;
          -  Unlikely to seek health care again at this site during the next two years&#xD;
&#xD;
          -  Not able or willing to provide informed consent. For patients not able to provide&#xD;
             informed consent: No guardian available or willing to provide IC&#xD;
&#xD;
          -  Medical emergency, underlying chronic medical condition, or other circumstances that&#xD;
             make adherence to the study unlikely, or participation in the study medically&#xD;
             inadvisable.&#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>Johan van Griensven, MD PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Institute of Tropical Medicine, Antwerp, Belgium</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ermias Diro, MD</last_name>
    <role>Study Director</role>
    <affiliation>College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Abdurafi Health Center</name>
      <address>
        <city>Abderafi</city>
        <state>Amhara</state>
        <country>Ethiopia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ethiopia</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>January 5, 2017</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>September 6, 2022</last_update_submitted>
  <last_update_submitted_qc>September 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>leishmaniasis, visceral, neglected, HIV, co-infection, asymptomatic, Ethiopia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leishmaniasis</mesh_term>
    <mesh_term>Leishmaniasis, Visceral</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/NCT03013673
org study id: ITM0915
nct id: NCT03013673
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
In this cohort study, the investigators will study the asymptomatic period preceding the
      onset of active Visceral Leishmaniasis (VL) in HIV-infected individuals from VL endemic
      regions in Ethiopia as an avenue to develop an evidence-based screen and treat strategy to
      prevent progression to active VL.
HIV co-infection drastically increases the risk of developing active VL. Clinical outcomes
      are dire in immune-compromised patients even with the best available treatment, and relapse
      is frequent. The incubation period may provide an important window of opportunity for a
      pre-emptive "screen an treat" approach in HIV co-infected patients to prevent progression
      from infection to the active disease. However, no recommendations exist to date due to lack
      of solid evidence.

      It is not known which patients are at highest risk of disease progression, which role
      parasite/host/HIV factors play in the asymptomatic infection phase, and what the diagnostic
      values of existing Leishmania infection markers are. Such information is needed to develop a
      prognostic clinical tool for the detection of HIV patients at high risk of developing active
      VL.

      Therefore, the aim is to study the asymptomatic period preceding the onset of active VL in
      HIV-infected individuals from VL endemic regions in Ethiopia as an avenue to develop an
      evidence-based screen and treat strategy to prevent progression to active VL. This will be a
      prospective cohort study with one year of follow-up for patients who remain VL free. Patients
      developing active VL during the study period will be followed until the end of the study
      duration.
observational model: Cohort
time perspective: Prospective
measure: Prevalence of asymptomatic Leishmania infection
time frame: January 2018
description: The proportion of individuals with asymptomatic Leishmania infection at enrolment, among all enrolled participants
measure: Incidence rate of asymptomatic Leishmania infection
time frame: January 2020
description: The number of individuals with newly diagnosed asymptomatic Leishmania infection per person-years at risk during follow-up, among participants without Leishmania infection at enrolment
measure: Evolution of Leishmania infection markers
time frame: January 2020
description: The proportions of individuals with positive test results for the different Leishmania infection markers at each follow-up visit
measure: Incidence rate of active VL
time frame: January 2020
description: The number of individuals who develop active VL per person-years at risk during follow-up, among all enrolled participants
measure: Risk factors for active VL
time frame: January 2020
description: The association between the risk to develop active VL during follow-up and demographic/clinical characteristics as well as HIV/host immunity/Leishmania infection markers from baseline onwards
measure: Prognostic tool for active VL
time frame: January 2021
description: A clinical decision algorithm, prioritizing and integrating identified risk factors, that is able to most efficiently predict the risk of developing active VL within 12 months
measure: Patterns in host immune markers for asymptomatic Leishmania infection
time frame: January 2020
description: The association between asymptomatic Leishmania infection and the levels of the different host immune markers, among participants tested for host immune markers
measure: Evolution of host immune markers
time frame: January 2020
description: The average levels of the different host immune markers at each follow-up visit
measure: Patterns in host immune markers for VL treatment failure
time frame: January 2021
description: The association between the risk of VL treatment failure and the levels and evolution of the different host immune markers, among participants who develop active VL and receive VL treatment
measure: Patterns in host immune markers for VL relapse
time frame: January 2021
description: The association between the risk of VL relapse and the levels and evolution of the different host immune markers, among participants who develop active VL
arm group label: HIV
description: HIV infected individuals residing in VL-endemic areas in Northern Ethiopia
intervention type: Other
intervention name: No intervention
description: No intervention
arm group label: HIV
All samples and sample left-overs (blood and urine) not used during the course of this study
      will be stored for 25 years after the end of the study.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Johan van Griensven, MD PhD
role: Study Chair
affiliation: Institute of Tropical Medicine, Antwerp, Belgium
last name: Ermias Diro, MD
role: Study Director
affiliation: College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
facility: 
country: Ethiopia
responsible party type: Sponsor
mesh term: Leishmaniasis
mesh term: Leishmaniasis, Visceral