Biomarkers in SCOTland CardiomyopatHy Registry (Bio-SCOTCH)

NCT ID: NCT06446271

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 750 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-06-26
• Study Completion Date: 2027-03-19

Brief Summary

Genetic cardiomyopathy is increasingly recognised and can lead to heart failure, arrhythmia and sudden cardiac death. Some gene positive patients have rapidly progressive disease with high rates of heart failure and cardiac transplantation, while others present with SCD. Other gene positive patients will never develop cardiomyopathy. At present, we cannot distinguish between these groups and rely on expensive and labour-intensive surveillance by electrocardiography, echocardiography and sometimes cardiac magnetic resonance imaging.

This study will investigate existing and novel biomarkers (including blood, urine electrocardiographic and imaging) at various stages of disease in patients with a personal or family history of TTN, MYBPC3, LMNA, FLNC or DSP gene variant, which are known to cause cardiomyopathy.

Detailed Description

There is a growing appreciation for the role that genetics play in the development of cardiomyopathy, which can lead to heart failure, arrhythmia and sudden cardiac death.

Increased use of genetic testing has identified numerous gene variants, which cause cardiomyopathy with dilated, hypertrophic, restrictive, non-dilated left ventricular and arrhythmogenic right ventricular phenotypes described.

Some gene variants cause a rapidly progressive cardiomyopathy with high rates of heart failure and cardiac transplantation, while others present with SCD, meaning that genotype-specific risk stratification and clinical surveillance is urgently needed. Some gene-positive individuals will never develop cardiomyopathy due to variable penetrance. At present, we cannot distinguish between these patients and therefore rely on expensive and labour-intensive surveillance by electrocardiography, echocardiography and sometimes cardiac magnetic resonance imaging. For every gene-positive affected individual with cardiomyopathy, cascade genetic testing will identify other gene-positive family members who are often asymptomatic and may not yet be affected.

A blood or urine-based biomarker that identifies pre-clinical disease or cardiomyopathy would allow for more efficient monitoring of gene positive people and could replace multiple, repeated electrocardiograms, echocardiograms and cardiac magnetic resonance imaging scans. A biomarker that accurately identifies pre-clinical cardiomyopathy could enable targeted early treatment. A biomarker that predicts future disease progression would be of high clinical value.

Conditions

Cardiomyopathies; Genetic Predisposition; Cardiomyopathy, Primary

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Gene positive participants (personal history of TTN, MYBPC3, LMNA, FLNC or DSP gene variant)

Pathogenic and likely pathogenic variants defined by American College of Medical Genetics guidelines.

Expected recruitment of: 300 TTN, 300 MYBPC3, up to 50 LMNA, up to 50 FLNC and up to 50 DSP

Plasma biomarker levels

Intervention Type: DIAGNOSTIC_TEST

This study will investigate existing and novel biomarkers (including blood, urine electrocardiographic and imaging) at various stages of disease in patients with a personal or family history of TTN, MYBPC3, LMNA, FLNC or DSP gene variant, which are known to cause cardiomyopathy.

Cardiomyopathy will be defined per European Society of Cardiology cardiomyopathy guidelines and heart failure stage will be defined per American Heart Associate guidelines.

Gene negative controls (family history of TTN, MYBPC3, LMNA, FLNC or DSP gene variant)

Expected recruitment of 50 patients.

Plasma biomarker levels

Intervention Type: DIAGNOSTIC_TEST

This study will investigate existing and novel biomarkers (including blood, urine electrocardiographic and imaging) at various stages of disease in patients with a personal or family history of TTN, MYBPC3, LMNA, FLNC or DSP gene variant, which are known to cause cardiomyopathy.

Cardiomyopathy will be defined per European Society of Cardiology cardiomyopathy guidelines and heart failure stage will be defined per American Heart Associate guidelines.

Interventions

Plasma biomarker levels

This study will investigate existing and novel biomarkers (including blood, urine electrocardiographic and imaging) at various stages of disease in patients with a personal or family history of TTN, MYBPC3, LMNA, FLNC or DSP gene variant, which are known to cause cardiomyopathy.

Cardiomyopathy will be defined per European Society of Cardiology cardiomyopathy guidelines and heart failure stage will be defined per American Heart Associate guidelines.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Electrocardiogram; Echocardiogram; Cardiac magnetic resonance imaging; 24-hour Holter monitor; Questionnaires (Kansas City Cardiomyopathy Questionnaire & General Practice Physical Activity Questionnaire); Urine biomarker levels

Eligibility Criteria

Inclusion Criteria

• Male or female ≥10 years of age
• Written informed consent / assent
• Pathogenic or likely pathogenic variant in a cardiomyopathy gene (TTN, LMNA, MYBPC3, DSP, FLNC) or undergoing predictive genetic testing (if negative these people would be invited to enter the control arm)

Exclusion Criteria

• Unable to consent.
• Geographical / social reasons preventing attending study centre
• Unable to complete study assessments.
• Severe non-cardiac disease expected to reduce life expectancy < 5 years
• Current participation in a blinded drug interventional trial (or treatment within 4 weeks)

• Minimum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Glasgow

OTHER

Sponsor Role: collaborator

Roche Diagnostics GmbH

INDUSTRY

Sponsor Role: collaborator

NHS Greater Glasgow and Clyde

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Caroline J Coats, MBBS, PhD

Role: CONTACT

Caroline.Coats@glasgow.ac.uk

0141 451 6121

Rachel C Myles, MBBS, PhD

Role: CONTACT

Rachel.Myles@glasgow.ac.uk

0141 451 6121

Facility Contacts

Caroline J Coats, MBBS, PhD

Role: primary

Caroline.Coats@glasgow.ac.uk

Fraser C Goldie, MBChB

Role: backup

Fraser.Goldie@glasgow.ac.uk

Other Identifiers

GN23CA296

Identifier Type: -

Identifier Source: org_study_id