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Genetic Susceptibility to Rheumatic Heart Disease in the Pacific Region

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ClinicalTrials.gov Identifier: NCT02188862
Recruitment Status : Completed
First Posted : July 14, 2014
Last Update Posted : July 15, 2014
Sponsor:
Collaborators:
Ministry of Health, Fiji
Fiji National University
Institut National de la Santé Et de la Recherche Médicale, France
Institut Necker Enfants Malades
Centre Hospitalier Territorial de Nouvelle-Calédonie
University of Melbourne
Information provided by (Responsible Party):
University of Oxford

Tracking Information
First Submitted Date July 10, 2014
First Posted Date July 14, 2014
Last Update Posted Date July 15, 2014
Study Start Date September 2012
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 11, 2014)
Rheumatic heart disease diagnosis [ Time Frame: At enrolment ]
Diagnosis of rheumatic heart disease as layout in enrolment criteria for cases.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: July 11, 2014)
Mitral stenosis diagnosis [ Time Frame: At enrolment ]
History or echocardiographic diagnosis of mitral stenosis
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Genetic Susceptibility to Rheumatic Heart Disease in the Pacific Region
Official Title Genome-wide Association Study of Susceptibility to Rheumatic Heart Disease in Fiji and New Caledonia
Brief Summary 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.
Detailed Description

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.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Retrospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Blood collected from all participants for extraction of DNA
Sampling Method Non-Probability Sample
Study Population

Cases:

  • Prevalent and incident cases of rheumatic heart disease ascertained from disease registers, primary care clinics and hospital services.

New Controls:

  • Individuals volunteering from communities where cases were identified.

Existing Controls:

  • Individuals from this region who have previously been recruited to population genetics research studies.
Condition
  • Rheumatic Heart Disease
  • Mitral Stenosis
Intervention Not Provided
Study Groups/Cohorts
  • Rheumatic heart disease cases
    Patients with rheumatic heart disease as defined in the case criteria
  • Population controls
    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)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: July 11, 2014)
2372
Original Actual Enrollment Same as current
Actual Study Completion Date December 2013
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria
  1. Cases

    1. Inclusion Criteria:

      • Diagnosis of rheumatic heart disease based on one of:

        • World Heart Federation definite echocardiographic criteria
        • World Heart Federation borderline echocardiographic criteria and history of acute rheumatic fever
        • Mitral stenosis with valve area less than 2.0 cm2
        • Previous surgery for rheumatic heart disease
    2. Exclusion Criteria:

      • Age less than five years
      • Inability to give consent
  2. New Controls

    1. Inclusion criteria:

      • Healthy individual living in a community where cases were identified
    2. Exclusion Criteria:

      • Past medical history or systems suggestive of rheumatic heart disease, acute rheumatic fever or other valvular heart disease
      • Age less than five years
      • Inability to give consent
Sex/Gender
Sexes Eligible for Study: All
Ages 5 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Fiji,   New Caledonia,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT02188862
Other Study ID Numbers PACIFICRHDGEN
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party University of Oxford
Study Sponsor University of Oxford
Collaborators
  • Ministry of Health, Fiji
  • Fiji National University
  • Institut National de la Santé Et de la Recherche Médicale, France
  • Institut Necker Enfants Malades
  • Centre Hospitalier Territorial de Nouvelle-Calédonie
  • University of Melbourne
Investigators
Principal Investigator: Tom Parks, MRCP DTM&H University of Oxford
Principal Investigator: Mariana Mirabel, MD Institut National de la Santé Et de la Recherche Médicale, France
Principal Investigator: Andrew C Steer, FRACP PhD University of Melbourne
Study Chair: Adrian VS Hill, DPhil DM University of Oxford
PRS Account University of Oxford
Verification Date July 2014