Defining the Genetics, Biomarkers and Outcomes for Dilated Cardiomyopathy

NCT ID: NCT03843255

Last Updated: 2022-03-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

2000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-01-09

Study Completion Date

2027-07-22

Brief Summary

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Finding new ways to diagnose and treat Dilated Cardiomyopathy (DCM) could improve the health and well-being of patients with this condition. The main aim of this research study is to help develop better ways of diagnosing and treating patients with DCM. The information that is collected may help develop tailored treatments for patients with this disease in the future. This research study will recruit patients with DCM from a number of centres across England and follow their health over a period of years. Patients will give some blood samples for a type of genetic test called whole genome sequencing (WGS) to look for genetic changes. Patients will also have a magnetic resonance imaging (MRI) scan of their heart to look for any changes in the heart such as scarring, and check their heart function. The aim of this study is to discover if using WGS and MRI can improve the diagnosis of DCM. Another aim of the study is to look at how genetic changes and scarring in the heart may affect the progress of the disease.

Studying patients with DCM may also help the investigators learn more about diagnosing and treating other diseases of the heart. The second aim of this study is to see whether using WGS and MRI scanning can also be useful in other types of heart diseases which might be affected by genetic changes or scarring in the heart.

Detailed Description

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This study will recruit patients from a number of hospitals in England and study them over a number of years. The study will be divided in 2 parts. Part 1 will recruit patients with a diagnosis of DCM, Part 2 will recruit patients diagnosed with other heritable cardiovascular disorders. Family members of patients may be invited to take part in the study. Children may also be approached to take part in the study.

Patients will attend for a baseline visit for a cardiovascular magnetic resonance (CMR) scan, completion of quality of life questionnaires, collection of blood samples for whole genome sequencing and biomarker analysis, and collection of clinical data. Collection of health information via national registries including Office of National Statistics (ONS) and Hospital Episodes Statistics (HES) will be continued over the patients's lifetime. This will not require any direct contact with the participant.

Recruitment will take place over a 3 year period, with annual completion of questionnaires at patients scheduled hospital visits. If the patient is not scheduled to attend the hospital for regular follow up, then patients may complete the questionnaires via an online system or over the telephone. Patients will be asked to complete questionnaires annually for 5 years. Sub-sets of patients may be invited for additional tests including exercise testing, and stress perfusion scans. These tests will not form part of the core tests for the study, and patients may choose not to have them. Separate informed consent will be obtained from participants for any additional tests.

If patients are having clinical diagnostic tests that involve the removal of tissue, they may be asked to donate any surplus tissue sample, or be asked to provide their consent to collect an additional tissue sample. Separate informed consent will be obtained from participants for donation of additional tissue samples.

Where patients are scheduled to have a CMR scan as part of their routine clinical care, an additional CMR scan for research purposes may not be required.

Children will not be asked to complete any annual questionnaires, health information will be collected via ONS and HES.

Family members of patients who take part in the study will only be asked to donate a blood or saliva sample, and provide consent to collection of their health information via ONS and HES records. They will not have any clinical tests such as CMR.

Conditions

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Dilated Cardiomyopathy Cardiovascular Diseases

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

OTHER

Study Groups

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Part 1: Dilated Cardiomyopathy patients

Approximately 1200 patients recruited prospectively from participating sites with a diagnosis of Dilated Cardiomyopathy (DCM). Will also include approximately 800 retrospective patients diagnosed with DCM currently biobanked by the lead site.

Part 1: DCM Cohort

Intervention Type OTHER

Patients with a confirmed diagnosis of DCM will have samples that undergo whole genome sequencing and biomarker analysis

Part 2: Heritable Cardiovascular Disease

Patients may be recruited with other diagnosed heritable cardiovascular disorders. Family members of patients may be invited to take part in the study. Children may also be approached to take part in the study.

Part 2: Heritable CV Diseases and Family Members

Intervention Type OTHER

Biomarker analysis will be undertaken on samples

Interventions

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Part 1: DCM Cohort

Patients with a confirmed diagnosis of DCM will have samples that undergo whole genome sequencing and biomarker analysis

Intervention Type OTHER

Part 2: Heritable CV Diseases and Family Members

Biomarker analysis will be undertaken on samples

Intervention Type OTHER

Other Intervention Names

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Whole genome sequencing and biomarker analysis Biomarker analysis

Eligibility Criteria

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Inclusion Criteria

* Male or female participants of any age
* Capacity to provide informed consent
* Patients with a confirmed diagnosis of DCM
* Affected family members of patients meeting diagnostic criteria for DCM


* Males or females of any age
* Capacity to provide informed consent
* Patients with hypokinetic non-dilated cardiomyopathy, or
* Family members of DCM patients with possible or probable DCM or
* Patients with a confirmed diagnosis of heritable cardiovascular disease or
* Family members of patients with heritable cardiovascular disease, both affected and unaffected

Exclusion Criteria

* DCM attributed to chemotoxicity (from chemotherapeutic agents, drugs of abuse)
* DCM attributed to systemic inflammatory myopathies (eg sarcoid, systemic lupus erythematosus)
* Patients who lack capacity to consent for themselves
* Patients with a confirmed history of coronary artery disease, assessed using standard UK clinical practice guidelines, defined as one or more of the following:-

* \>50% narrowing, any major epicardial coronary artery on invasive or computed tomography coronary angiography
* CMR suggestive of previous myocardial infarction of ≥2 segments of ≥50% infarction of the LV wall
* Previous percutaneous coronary intervention or coronary bypass surgery
* History of primary valvular heart disease or congenital heart disease
* Severe, untreated or untreatable hypertension (systolic blood pressures routinely \>180 mm Hg and/or diastolic blood pressures \>120 mm Hg)

PART 2


* Patients who lack capacity to consent for themselves
* Patients with a confirmed history of coronary artery disease, assessed using standard UK clinical practice guidelines, defined as one or more of the following:-

* \>50% narrowing, any major epicardial coronary artery on invasive or computed tomography coronary angiography
* CMR suggestive of previous myocardial infarction of ≥2 segments of ≥50% infarction of the LV wall
* Previous percutaneous coronary intervention or coronary bypass surgery
* History of primary valvular heart disease or congenital heart disease
* Severe, untreated or untreatable hypertension (systolic blood pressures routinely \>180 mm Hg and/or diastolic blood pressures \>120 mm Hg)
Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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British Heart Foundation

OTHER

Sponsor Role collaborator

Royal Brompton & Harefield NHS Foundation Trust

OTHER

Sponsor Role collaborator

Imperial College London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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James Ware

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

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Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Site Status RECRUITING

Glenfield Hospital

Leicester, , United Kingdom

Site Status RECRUITING

Liverpool Heart and Chest Hospital NHS Foundation Trust

Liverpool, , United Kingdom

Site Status RECRUITING

Royal Brompton & Harefield NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Oxford University Hospitals NHS Foundation Trust

Oxford, , United Kingdom

Site Status RECRUITING

Southampton General Hospital

Southampton, , United Kingdom

Site Status NOT_YET_RECRUITING

Countries

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United Kingdom

Central Contacts

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James Ware

Role: CONTACT

0330 128 2294

Chief Investigator

Role: CONTACT

0330 128 2294

Facility Contacts

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Dr John Greenwood

Role: primary

Prof Gerry McCann

Role: primary

Dr David Wright

Role: primary

Dr Sanjay Prasad

Role: primary

Dr Masliza Mahmod

Role: primary

Dr Charles Peebles

Role: primary

Other Identifiers

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18IC4391

Identifier Type: -

Identifier Source: org_study_id

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