Rheumatic Heart DiseaseNCT02188862
Genetic Susceptibility to Rheumatic Heart Disease in the Pacific Region
An observational study of Rheumatic Heart Disease and Mitral Stenosis, run by University of Oxford at 3 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 years and olderHealthy volunteers can take part
- Conditions the study is for
- Rheumatic Heart Disease, Mitral Stenosis
- How many people
- 2,372 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Sep 2012to Dec 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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.
- Cases
- 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
- Exclusion Criteria:
- Age less than five years
- Inability to give consent
- New Controls
- Inclusion criteria:
- Healthy individual living in a community where cases were identified
- 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
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
Fiji1 site
Colonial War Memorial Hospital
Suva
New Caledonia1 site
Centre Hospitalier Territorial de Nouvelle Caledonie
Noumea
United Kingdom1 site
Wellcome Trust Centre for Human Genetics, University of Oxford
Oxford, OX3 7BN
About this study
Official title: Genome-wide Association Study of Susceptibility to Rheumatic Heart Disease in Fiji and New Caledonia
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.
Read the 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.
- Conditions
- Rheumatic Heart Disease, Mitral Stenosis
- Keywords
- Rheumatic heart disease, Acute rheumatic fever, Group A streptococcal disease, Streptococcus pyogenes, Genetics, Oceania
- Medical subject headings
- Rheumatic Heart Disease, Mitral Valve Stenosis, Rheumatic Fever, Streptococcal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rheumatic heart disease diagnosis
Diagnosis of rheumatic heart disease as layout in enrolment criteria for cases.
Measured: At enrolment
Secondary outcomes (1)
Mitral stenosis diagnosis
History or echocardiographic diagnosis of mitral stenosis
Measured: At enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2014 (estimated)
- Study startSep 2012
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatic Heart DiseaseStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 2,372 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Sponsor
- Investigators
- Tom Parks, MRCP DTM&H, Principal investigator, University of OxfordMariana Mirabel, MD, Principal investigator, Institut National de la Santé Et de la Recherche Médicale, FranceAndrew C Steer, FRACP PhD, Principal investigator, University of MelbourneAdrian VS Hill, DPhil DM, Study chair, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02188862
- Sponsor's protocol ID
- PACIFICRHDGEN
- Status last verified
- Jul 2014
- First submitted
- 10 Jul 2014
- Last updated
- 15 Jul 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genome-wide Association Study of Susceptibility to Rheumatic Heart Disease in Fiji and New Caledonia
- ClinicalTrials.gov ID
- NCT02188862
- Acronym / sponsor ID
- PACIFICRHDGEN
- Conditions
- Rheumatic Heart Disease, Mitral Stenosis
- Keywords
- Rheumatic heart disease, Acute rheumatic fever, Group A streptococcal disease, Streptococcus pyogenes, Genetics, Oceania
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,372 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- 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
- Study start
- Sep 2012
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 14 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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) |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Rheumatic heart disease diagnosis
Time frame: At enrolment
Diagnosis of rheumatic heart disease as layout in enrolment criteria for cases.
1 secondary outcome
Mitral stenosis diagnosis
Time frame: At enrolment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2014.
- Link to study documents and protocolsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tom Parks, MRCP DTM&H principal investigator
University of Oxford
Mariana Mirabel, MD principal investigator
Institut National de la Santé Et de la Recherche Médicale, France
Andrew C Steer, FRACP PhD principal investigator
University of Melbourne
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rheumatic Heart Disease and Mitral Stenosis, run by University of Oxford at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Fiji, New Caledonia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rheumatic heart disease diagnosis (time frame: At enrolment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2014.