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/NCT05981378</url>
    </required_header>
    <id_info>
      <org_study_id>210828</org_study_id>
      <nct_id>NCT05981378</nct_id>
    </id_info>
    <brief_title>Genomic Approaches to Dissect Human Host-pathogen Interactions in the Amazonian Rainforest</brief_title>
    <acronym>PATHO-NAT</acronym>
    <official_title>Genomic Approaches to Dissect Human Host-pathogen Interactions in the Amazonian Rainforest</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Universidad Peruana Cayetano Heredia</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Institut Pasteur</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Universidad Peruana Cayetano Heredia</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>
        This observational study, aims to characterize with a multi-omic approach, the impact of host&#xD;
        genetics and the pathogenic environment on immune response variation in Native Amazonians in&#xD;
        comparison with Mestizo Amazonian, a severely underrepresented population in genomic studies.&#xD;
  &#xD;
        Various samples will be taken from the participants, including blood, urine, saliva, etc.&#xD;
        From the blood sample, peripheral blood mononuclear cells will be obtained and will give us&#xD;
        information about the differences between immune response variation of Amazonian population.&#xD;
        From the other samples we will be able to obtain additional information on the risk factors&#xD;
        related to the difference in the immune response of the participants.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The Amazon rainforest is characterized by adverse climatic conditions and a great diversity&#xD;
        of pathogenic microorganisms that, consequently, would generate a selective pressure on the&#xD;
        human immune response with a high impact on mortality. Some of the best characterized&#xD;
        examples of human genetic adaptation have been related to infections; for example, the&#xD;
        alleles causing sickle cell anemia, thalassemia and malaria. In addition, the introduction of&#xD;
        infectious diseases from the &quot;old world&quot; during Spanish colonization in the 15th century and&#xD;
        the urbanization of the last few centuries in the Amazon has also generated rapid adaptation&#xD;
        that could drive variation in immune response. However, the evolutionary mechanisms that&#xD;
        contributed to the adaptation of human defense against the aforementioned phenomena and&#xD;
        events in this region are poorly understood. For this reason, studying these human genetic&#xD;
        mechanisms in native populations would allow us to identify new genes that would be&#xD;
        associated with resistance to infections, and also to explore the signs of rapid adaptation&#xD;
        to the environment to which Amazonian populations have been exposed throughout their history.&#xD;
  &#xD;
        We propose to study the variation of the immune system in Amazonian populations, studying&#xD;
        together the degree of diversity with different approaches: genomic, epi-genomic and&#xD;
        transcriptomic of the host and viral exposome, taking into consideration sociodemographic&#xD;
        characteristics and comorbidities, which may shape the immune response. This study will&#xD;
        provide new insights into variants in the human genome that affect the immune response,&#xD;
        thereby increasing our understanding of the etiology and susceptibility to immune-related&#xD;
        diseases, mainly tropical infectious diseases. Because human genetic studies are&#xD;
        underrepresented in Native American populations, the knowledge gained would reduce the&#xD;
        existing inequality in health knowledge between Native and non-Native populations.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 20, 2023</start_date>
    <completion_date type="Anticipated">January 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">November 20, 2023</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Other</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Genes showing different transcriptional profiles and methylation pattern according environment, genetic ancestry and past viral exposure</measure>
      <time_frame>Baseline</time_frame>
      <description>We will measure genome-wide expression profiles in peripheral blood mononuclear cells after stimulation for 6 hours with: (i) dengue virus, a major public health burden in the region, (ii) gardiquimod, an imidazoquinoxaline compound that activates toll like receptor 7/toll like receptor 8, able to sense viruses and intracellular pathogens; and (iii) lipopolysaccharide, a toll like receptor 4 agonist, to obtain a general view of responses to viruses and bacteria.&#xD;
  Gene expression profiles will be measured using RNA-seq.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Genetic and epigenetic diversity of amazonian population</measure>
      <time_frame>Baseline</time_frame>
      <description>Using saliva from participants as source of DNA, we will perform whole-genome sequencing (WGS) at 8-10xcoverage.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Impact of microbial exposures on immune response</measure>
      <time_frame>Baseline</time_frame>
      <description>The viral exposome will be characterized in the 300 donors using a new tool call &quot;VirScan&quot;, which identifies antibodies against &gt;600 pathogens and allergens, including viruses (&gt;1,200 viral strains) that are highly prevalent in the Amazonian, such as dengue, hepatitis B/C/D, or Mayaro virus.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Genetic variants associated wit transcriptional response to immune activation and DNA methylation variation</measure>
      <time_frame>Baseline</time_frame>
      <description>We will assess the host genetic factors controlling transcriptional responses and methylated DNA levels by mapping expression and methylation quantitative trait loci (eQTL and methylated eQTLs, respectively).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Demographic and admixture history of amazonian population</measure>
      <time_frame>Baseline</time_frame>
      <description>Using saliva from participants as source of DNA, we will perform whole-genome sequencing (WGS) at 8-10xcoverage.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Natural selection role in shaping immune response variation in Amazonians</measure>
      <time_frame>Baseline</time_frame>
      <description>We will employ an enrichment approach to test whether eQTLs, associated to specific cell-types or conditions, have been preferentially targeted by selection.</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">300</enrollment>
    <condition>Host-Pathogen Interactions</condition>
    <arm_group>
      <arm_group_label>Native Amazonian group</arm_group_label>
      <description>Amazonian people that belongs to a indigenous community located in the Peruvian Amazon</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Urban Amazonian mestizos group</arm_group_label>
      <description>Amazonian mestizo people that lives on a urban district in the Peruvian Amazon</description>
    </arm_group>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Whole Blood, serum, plasma, saliva, feces, peripheral blood mononuclear cells,&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Amazonian Peruvian Native American and Amazonian mestizo population between 2023-2024&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  People over 18 years of age who agree to participate in the study and sign the&#xD;
               informed consent&#xD;
  &#xD;
            -  People whose parents and grandparents were born in the Peruvian Amazon.&#xD;
  &#xD;
            -  For volunteers from native communities, whose parents and grandparents belong to the&#xD;
               same native community.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  People who do not wish to have 40 mL of blood taken&#xD;
  &#xD;
            -  People who are passing through a febrile illness (fever during the last 5 days to the&#xD;
               date of enrollment).&#xD;
  &#xD;
            -  Pregnant women&#xD;
  &#xD;
            -  People over 65 years old&#xD;
  &#xD;
            -  Breastfeeding women.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Meddly Santoalla, PhD</last_name>
      <phone>+51 914068043</phone>
      <email>meddly.santolalla.r@upch.pe</email>
    </overall_contact>
    <link>
      <url>https://investigacion.cayetano.edu.pe/duari/ciei/</url>
      <description>Web page of the ethical review board of Universidad Peruana Cayetano Heredia</description>
    </link>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>July 31, 2023</last_update_submitted>
    <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Tropical Rainforest</keyword>
    <keyword>Genomics</keyword>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <study_docs>
      <study_doc>
        <doc_type>Study Protocol</doc_type>
        <doc_url>https://drive.google.com/drive/folders/1SJk21vz3MOlaF8tSVnwPlwo9sxmmewZp?usp=drive_link</doc_url>
        <doc_comment>Google drive link to visualize the study protocol in Spanish and English</doc_comment>
      </study_doc>
    </study_docs>
    <!-- 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/NCT05981378
  org study id: 210828
  nct id: NCT05981378
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This observational study, aims to characterize with a multi-omic approach, the impact of host
        genetics and the pathogenic environment on immune response variation in Native Amazonians in
        comparison with Mestizo Amazonian, a severely underrepresented population in genomic studies.
  
        Various samples will be taken from the participants, including blood, urine, saliva, etc.
        From the blood sample, peripheral blood mononuclear cells will be obtained and will give us
        information about the differences between immune response variation of Amazonian population.
        From the other samples we will be able to obtain additional information on the risk factors
        related to the difference in the immune response of the participants.
  The Amazon rainforest is characterized by adverse climatic conditions and a great diversity
        of pathogenic microorganisms that, consequently, would generate a selective pressure on the
        human immune response with a high impact on mortality. Some of the best characterized
        examples of human genetic adaptation have been related to infections; for example, the
        alleles causing sickle cell anemia, thalassemia and malaria. In addition, the introduction of
        infectious diseases from the "old world" during Spanish colonization in the 15th century and
        the urbanization of the last few centuries in the Amazon has also generated rapid adaptation
        that could drive variation in immune response. However, the evolutionary mechanisms that
        contributed to the adaptation of human defense against the aforementioned phenomena and
        events in this region are poorly understood. For this reason, studying these human genetic
        mechanisms in native populations would allow us to identify new genes that would be
        associated with resistance to infections, and also to explore the signs of rapid adaptation
        to the environment to which Amazonian populations have been exposed throughout their history.
  
        We propose to study the variation of the immune system in Amazonian populations, studying
        together the degree of diversity with different approaches: genomic, epi-genomic and
        transcriptomic of the host and viral exposome, taking into consideration sociodemographic
        characteristics and comorbidities, which may shape the immune response. This study will
        provide new insights into variants in the human genome that affect the immune response,
        thereby increasing our understanding of the etiology and susceptibility to immune-related
        diseases, mainly tropical infectious diseases. Because human genetic studies are
        underrepresented in Native American populations, the knowledge gained would reduce the
        existing inequality in health knowledge between Native and non-Native populations.
  observational model: Other
  time perspective: Prospective
  measure: Genes showing different transcriptional profiles and methylation pattern according environment, genetic ancestry and past viral exposure
  time frame: Baseline
  description: We will measure genome-wide expression profiles in peripheral blood mononuclear cells after stimulation for 6 hours with: (i) dengue virus, a major public health burden in the region, (ii) gardiquimod, an imidazoquinoxaline compound that activates toll like receptor 7/toll like receptor 8, able to sense viruses and intracellular pathogens; and (iii) lipopolysaccharide, a toll like receptor 4 agonist, to obtain a general view of responses to viruses and bacteria.
  Gene expression profiles will be measured using RNA-seq.
  measure: Genetic and epigenetic diversity of amazonian population
  time frame: Baseline
  description: Using saliva from participants as source of DNA, we will perform whole-genome sequencing (WGS) at 8-10xcoverage.
  measure: Impact of microbial exposures on immune response
  time frame: Baseline
  description: The viral exposome will be characterized in the 300 donors using a new tool call "VirScan", which identifies antibodies against >600 pathogens and allergens, including viruses (>1,200 viral strains) that are highly prevalent in the Amazonian, such as dengue, hepatitis B/C/D, or Mayaro virus.
  measure: Genetic variants associated wit transcriptional response to immune activation and DNA methylation variation
  time frame: Baseline
  description: We will assess the host genetic factors controlling transcriptional responses and methylated DNA levels by mapping expression and methylation quantitative trait loci (eQTL and methylated eQTLs, respectively).
  measure: Demographic and admixture history of amazonian population
  time frame: Baseline
  description: Using saliva from participants as source of DNA, we will perform whole-genome sequencing (WGS) at 8-10xcoverage.
  measure: Natural selection role in shaping immune response variation in Amazonians
  time frame: Baseline
  description: We will employ an enrichment approach to test whether eQTLs, associated to specific cell-types or conditions, have been preferentially targeted by selection.
  arm group label: Native Amazonian group
  description: Amazonian people that belongs to a indigenous community located in the Peruvian Amazon
  arm group label: Urban Amazonian mestizos group
  description: Amazonian mestizo people that lives on a urban district in the Peruvian Amazon
  Whole Blood, serum, plasma, saliva, feces, peripheral blood mononuclear cells,
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Meddly Santoalla, PhD
  phone: +51 914068043
  email: meddly.santolalla.r@upch.pe
  url: https://investigacion.cayetano.edu.pe/duari/ciei/
  description: Web page of the ethical review board of Universidad Peruana Cayetano Heredia
  responsible party type: Sponsor
  sharing ipd: No
  study doc: 