Defining the Genetics, Biomarkers and Outcomes for Dilated Cardiomyopathy

NCT03843255 | Active Not Recruiting

• 1 other identifier: 18IC4391
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Cardiovascular Diseases; Dilated Cardiomyopathy

Outcome Measures

Primary Outcomes (2)

• The incidence of major adverse cardiovascular events over 5 years

  The incidence of major adverse cardiovascular events over 5 years,defined as:- 1. Cardiovascular death 2. Major arrhythmic events (ventricular fibrillation, unstable sustained ventricular tachycardia, appropriate implantable cardioverter-defibrillator delivered shock, and aborted sudden cardiac death) 3. Major heart failure events (heart transplantation, left ventricular assist device implantation, unplanned heart failure hospitalisation) We will recruit a group of patients that could be asked to take part in future research projects to evaluate personalised treatments for DCM and other cardiovascular diseases.

  5 years

• Incidence of novel gene variants as assessed using whole genome sequencing

  Identifying the gene variants contributing to DCM and specifically the incidence of these variants in the target population.

  5 years

Study Arms (2)

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.

Other: Part 1: DCM Cohort

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.

Other: Part 2: Heritable CV Diseases and Family Members

Interventions

Part 1: DCM Cohort OTHER

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

Also known as: Whole genome sequencing and biomarker analysis

Part 1: Dilated Cardiomyopathy patients

Part 2: Heritable CV Diseases and Family Members OTHER

Biomarker analysis will be undertaken on samples

Also known as: Biomarker analysis

Part 2: Heritable Cardiovascular Disease

Eligibility Criteria

• Age: Up to 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* Patients of any age with diagnosed DCM (part 1), and * Their family members with other heritable cardiovasacular disease (affected and unaffected), or other eligible patients with hypokinetic non-dilated cardiomyopathy (part 2)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Imperial College London: lead
• British Heart Foundation: collaborator
• Royal Brompton & Harefield NHS Foundation Trust: collaborator

Study Sites (6)

Leeds Teaching Hospitals NHS Trust

Leeds, LS1 3EX, United Kingdom

Location

Glenfield Hospital

Leicester, LE3 9QP, United Kingdom

Location

Liverpool Heart and Chest Hospital NHS Foundation Trust

Liverpool, L14 3PE, United Kingdom

Location

Royal Brompton & Harefield NHS Foundation Trust

London, SW3 6NP, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

1. Blood- plasma and serum 2. Saliva 3. Collection of additional tissue samples (myocardial, skeletal, skin) from planned clinical procedures (where applicable)

MeSH Terms

Conditions

Cardiomyopathy, Dilated; Cardiovascular Diseases

Interventions

Whole Genome Sequencing

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• James Ware

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2019
• First Posted: February 18, 2019
• Study Start: January 9, 2020
• Primary Completion (Estimated): July 22, 2027
• Study Completion (Estimated): June 16, 2029
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: During planning (January 2018) and throughout the study recruitment and follow-up period (Dec 2022)
• Access Criteria: Provided through secure data transfer mechanisms approved by Imperial College London and secure email

Locations

GB (6)