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Genetic Susceptibility to Rheumatic Heart Disease in the Pacific Region

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Study Description
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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.

Condition or disease
Rheumatic Heart Disease Mitral Stenosis

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 Design
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Study Type : Observational
Actual Enrollment : 2372 participants
Observational Model: Case-Control
Time Perspective: Retrospective
Official Title: Genome-wide Association Study of Susceptibility to Rheumatic Heart Disease in Fiji and New Caledonia
Study Start Date : September 2012
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Diseases

Groups and Cohorts
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Group/Cohort
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)


Outcome Measures
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Primary Outcome Measures :
  1. Rheumatic heart disease diagnosis [ Time Frame: At enrolment ]
    Diagnosis of rheumatic heart disease as layout in enrolment criteria for cases.


Secondary Outcome Measures :
  1. Mitral stenosis diagnosis [ Time Frame: At enrolment ]
    History or echocardiographic diagnosis of mitral stenosis


Biospecimen Retention:   Samples With DNA
Blood collected from all participants for extraction of DNA

Eligibility Criteria
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Ages Eligible for Study:   5 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02188862


Locations
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Fiji
Colonial War Memorial Hospital
Suva, Fiji
New Caledonia
Centre Hospitalier Territorial de Nouvelle Caledonie
Noumea, New Caledonia
United Kingdom
Wellcome Trust Centre for Human Genetics, University of Oxford
Oxford, United Kingdom, OX3 7BN
Sponsors and Collaborators
University of Oxford
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
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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
More Information
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Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT02188862    
Other Study ID Numbers: PACIFICRHDGEN
First Posted: July 14, 2014    Key Record Dates
Last Update Posted: July 15, 2014
Last Verified: July 2014
Keywords provided by University of Oxford:
Rheumatic heart disease
Acute rheumatic fever
Group A streptococcal disease
 Streptococcus pyogenes
Genetics
Oceania
Additional relevant MeSH terms:
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Rheumatic Heart Disease
Rheumatic Diseases
Heart Diseases
Mitral Valve Stenosis
Cardiovascular Diseases
Musculoskeletal Diseases
Connective Tissue Diseases
 Rheumatic Fever
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
Heart Valve Diseases