<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/NCT02188862</url>
  </required_header>
  <id_info>
    <org_study_id>PACIFICRHDGEN</org_study_id>
    <nct_id>NCT02188862</nct_id>
  </id_info>
  <brief_title>Genetic Susceptibility to Rheumatic Heart Disease in the Pacific Region</brief_title>
  <official_title>Genome-wide Association Study of Susceptibility to Rheumatic Heart Disease in Fiji and New Caledonia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Health, Fiji</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fiji National University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut Necker Enfants Malades</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Centre Hospitalier Territorial de Nouvelle-Calédonie</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Melbourne</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Oxford</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate whether there are genetic differences between&#xD;
      patients with rheumatic heart disease and members of the general population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators will micro-array genotype approximately 300,000 single nucleotide&#xD;
      polymorphisms (SNP) using DNA samples from patients with rheumatic heart disease (cases) from&#xD;
      New Caledonia and Fiji, and members of the general population (controls) from New Caledonia,&#xD;
      Vanuatu and Fiji. The investigators will perform standard quality control checks on the SNP&#xD;
      data using measures such as call rate, heterozygosity, duplication and relatedness, and&#xD;
      exclude variants on the basis of deviation from Hardy-Weinberg equilibrium and minor allele&#xD;
      frequency. We will also impute variants not present on the micro-array with reference to the&#xD;
      latest release of 1000 Genomes data and whole-genome sequence data from sixty Melanesian&#xD;
      individuals from New Caledonia from the phenotypic extremes in this study.&#xD;
&#xD;
      The investigators will conduct a discovery analysis in using a genome-wide association study&#xD;
      approach focusing on Oceanic cases and controls from the Francophone nations of New Caledonia&#xD;
      and Vanuatu. This analysis will be corrected for bias due to population stratification using&#xD;
      the Linear Mixed Model (LMM) and consider additive, dominant and recessive genetic models.&#xD;
      The investigators will then perform LMM association testing for variants with P-value in the&#xD;
      discovery analysis less than 1x10^-5 in Oceanic cases and controls from Fiji and combine the&#xD;
      association statistics by fixed-effects meta-analysis. The investigators will consider&#xD;
      variants with significant effects in the same direction in discovery and replication analyses&#xD;
      with combined P-value less than 1x10^-8 to have replicated. Unless there is clear evidence&#xD;
      that associated variants are specific to Oceanic populations, further replication analyses&#xD;
      for associated variants in cases and controls of Indian Descent from Fiji, as well as&#xD;
      individuals of other and admixed ethnicities from both Fiji and New Caledonia.&#xD;
&#xD;
      Recruitment completed in December 2013. After receipt of funding from the British Heart&#xD;
      Foundation, genotyping and analysis will begin in July 2014.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Rheumatic heart disease diagnosis</measure>
    <time_frame>At enrolment</time_frame>
    <description>Diagnosis of rheumatic heart disease as layout in enrolment criteria for cases.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mitral stenosis diagnosis</measure>
    <time_frame>At enrolment</time_frame>
    <description>History or echocardiographic diagnosis of mitral stenosis</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">2372</enrollment>
  <condition>Rheumatic Heart Disease</condition>
  <condition>Mitral Stenosis</condition>
  <arm_group>
    <arm_group_label>Rheumatic heart disease cases</arm_group_label>
    <description>Patients with rheumatic heart disease as defined in the case criteria</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Population controls</arm_group_label>
    <description>Individuals from the general population divided into new controls (recruited specifically for this study) and existing controls (recruited to previous population genetics studies in the region)</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood collected from all participants for extraction of DNA&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Cases:&#xD;
&#xD;
          -  Prevalent and incident cases of rheumatic heart disease ascertained from disease&#xD;
             registers, primary care clinics and hospital services.&#xD;
&#xD;
        New Controls:&#xD;
&#xD;
          -  Individuals volunteering from communities where cases were identified.&#xD;
&#xD;
        Existing Controls:&#xD;
&#xD;
          -  Individuals from this region who have previously been recruited to population genetics&#xD;
             research studies.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        1. Cases&#xD;
&#xD;
               1. Inclusion Criteria:&#xD;
&#xD;
                    -  Diagnosis of rheumatic heart disease based on one of:&#xD;
&#xD;
                         -  World Heart Federation definite echocardiographic criteria&#xD;
&#xD;
                         -  World Heart Federation borderline echocardiographic criteria and&#xD;
                            history of acute rheumatic fever&#xD;
&#xD;
                         -  Mitral stenosis with valve area less than 2.0 cm2&#xD;
&#xD;
                         -  Previous surgery for rheumatic heart disease&#xD;
&#xD;
               2. Exclusion Criteria:&#xD;
&#xD;
                    -  Age less than five years&#xD;
&#xD;
                    -  Inability to give consent&#xD;
&#xD;
          2. New Controls&#xD;
&#xD;
               1. Inclusion criteria:&#xD;
&#xD;
                    -  Healthy individual living in a community where cases were identified&#xD;
&#xD;
               2. Exclusion Criteria:&#xD;
&#xD;
                    -  Past medical history or systems suggestive of rheumatic heart disease, acute&#xD;
                       rheumatic fever or other valvular heart disease&#xD;
&#xD;
                    -  Age less than five years&#xD;
&#xD;
                    -  Inability to give consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tom Parks, MRCP DTM&amp;H</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Oxford</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mariana Mirabel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut National de la Santé Et de la Recherche Médicale, France</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Andrew C Steer, FRACP PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Melbourne</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Adrian VS Hill, DPhil DM</last_name>
    <role>Study Chair</role>
    <affiliation>University of Oxford</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Colonial War Memorial Hospital</name>
      <address>
        <city>Suva</city>
        <country>Fiji</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Territorial de Nouvelle Caledonie</name>
      <address>
        <city>Noumea</city>
        <country>New Caledonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellcome Trust Centre for Human Genetics, University of Oxford</name>
      <address>
        <city>Oxford</city>
        <zip>OX3 7BN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Fiji</country>
    <country>New Caledonia</country>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://users.ox.ac.uk/~clme1250/rhd_consortium/pacific.html</url>
    <description>Link to study documents and protocols</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 10, 2014</study_first_submitted>
  <study_first_submitted_qc>July 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 14, 2014</study_first_posted>
  <last_update_submitted>July 14, 2014</last_update_submitted>
  <last_update_submitted_qc>July 14, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 15, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rheumatic heart disease</keyword>
  <keyword>Acute rheumatic fever</keyword>
  <keyword>Group A streptococcal disease</keyword>
  <keyword>Streptococcus pyogenes</keyword>
  <keyword>Genetics</keyword>
  <keyword>Oceania</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rheumatic Heart Disease</mesh_term>
    <mesh_term>Rheumatic Diseases</mesh_term>
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Mitral Valve Stenosis</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>May 17, 2018</submitted>
    <returned>December 7, 2018</returned>
    <submitted>April 16, 2019</submitted>
    <returned>July 9, 2019</returned>
  </pending_results>
  <!-- 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/NCT02188862
org study id: PACIFICRHDGEN
nct id: NCT02188862
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to investigate whether there are genetic differences between
      patients with rheumatic heart disease and members of the general population.
The investigators will micro-array genotype approximately 300,000 single nucleotide
      polymorphisms (SNP) using DNA samples from patients with rheumatic heart disease (cases) from
      New Caledonia and Fiji, and members of the general population (controls) from New Caledonia,
      Vanuatu and Fiji. The investigators will perform standard quality control checks on the SNP
      data using measures such as call rate, heterozygosity, duplication and relatedness, and
      exclude variants on the basis of deviation from Hardy-Weinberg equilibrium and minor allele
      frequency. We will also impute variants not present on the micro-array with reference to the
      latest release of 1000 Genomes data and whole-genome sequence data from sixty Melanesian
      individuals from New Caledonia from the phenotypic extremes in this study.

      The investigators will conduct a discovery analysis in using a genome-wide association study
      approach focusing on Oceanic cases and controls from the Francophone nations of New Caledonia
      and Vanuatu. This analysis will be corrected for bias due to population stratification using
      the Linear Mixed Model (LMM) and consider additive, dominant and recessive genetic models.
      The investigators will then perform LMM association testing for variants with P-value in the
      discovery analysis less than 1x10^-5 in Oceanic cases and controls from Fiji and combine the
      association statistics by fixed-effects meta-analysis. The investigators will consider
      variants with significant effects in the same direction in discovery and replication analyses
      with combined P-value less than 1x10^-8 to have replicated. Unless there is clear evidence
      that associated variants are specific to Oceanic populations, further replication analyses
      for associated variants in cases and controls of Indian Descent from Fiji, as well as
      individuals of other and admixed ethnicities from both Fiji and New Caledonia.

      Recruitment completed in December 2013. After receipt of funding from the British Heart
      Foundation, genotyping and analysis will begin in July 2014.
observational model: Case-Control
time perspective: Retrospective
measure: Rheumatic heart disease diagnosis
time frame: At enrolment
description: Diagnosis of rheumatic heart disease as layout in enrolment criteria for cases.
measure: Mitral stenosis diagnosis
time frame: At enrolment
description: History or echocardiographic diagnosis of mitral stenosis
arm group label: Rheumatic heart disease cases
description: Patients with rheumatic heart disease as defined in the case criteria
arm group label: Population controls
description: Individuals from the general population divided into new controls (recruited specifically for this study) and existing controls (recruited to previous population genetics studies in the region)
Blood collected from all participants for extraction of DNA
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 5 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Tom Parks, MRCP DTM&H
role: Principal Investigator
affiliation: University of Oxford
last name: Mariana Mirabel, MD
role: Principal Investigator
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
last name: Andrew C Steer, FRACP PhD
role: Principal Investigator
affiliation: University of Melbourne
last name: Adrian VS Hill, DPhil DM
role: Study Chair
affiliation: University of Oxford
facility: 
facility: 
facility: 
country: Fiji
country: New Caledonia
country: United Kingdom
url: http://users.ox.ac.uk/~clme1250/rhd_consortium/pacific.html
description: Link to study documents and protocols
responsible party type: Sponsor
mesh term: Rheumatic Heart Disease
mesh term: Rheumatic Diseases
mesh term: Heart Diseases
mesh term: Mitral Valve Stenosis
submitted: May 17, 2018
returned: December 7, 2018
submitted: April 16, 2019
returned: July 9, 2019