Biomarkers in SCOTland CardiomyopatHy Registry (Bio-SCOTCH)

Recruiting

• Conditions: Cardiomyopathies; Cardiomyopathy, Primary; Genetic Predisposition
• Interventions: Diagnostic Test: Plasma biomarker levels

• Registration Number: NCT06446271
• Lead Sponsor: NHS Greater Glasgow and Clyde

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.

Study Timeline

• Study First Submitted: 2024-05-31
• Study First Submitted QC: 2024-05-31
• Study First Posted: 2024-06-06
• Study Start: 2024-06-26
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-01
• Last Update Posted: 2024-07-03
• Primary Completion: 2027-03-19
• Study Completion: 2027-03-19

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 750

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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Gene negative controls (family history of TTN, MYBPC3, LMNA, FLNC or DSP gene variant)	Plasma biomarker levels	Expected recruitment of 50 patients.
Gene positive participants (personal history of TTN, MYBPC3, LMNA, FLNC or DSP gene variant)	Plasma biomarker levels	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

Primary Outcome Measures

Name	Time	Method
Biomarker performance	3 years	Diagnostic performance of existing and novel biomarkers across the spectrum of disease in patients with pathogenic/ likely pathogenic TTN, MYBPC3, LMNA, FLNC or DSP gene variants.

Secondary Outcome Measures

Name	Time	Method
Natural history of genetic cardiomyopathies	3 years with long-term data linkage	Investigate the natural history of genetic cardiomyopathy due to variants in TTN, MYBPC3, LMNA, FLNC and DSP genes.
Biomarker correlation	3 years	Correlation of biomarkers with cardiac imaging measures of inflammation and myocardial fibrosis in genetic cardiomyopathies.
Prediction of cardiomyopathy progression	3 years with long-term data linkage	Investigation of biomarkers that can predict which patients (who are gene positive with cardiomyopathy) will have progressive cardiomyopathy, heart failure, arrhythmia, or die.
Prediction of cardiomyopathy development	3 years with long-term data linkage	Investigation of biomarkers that can predict which patients (who are gene positive without cardiomyopathy) will develop cardiomyopathy, heart failure, arrhythmia, or die

Trial Locations

Locations (1)

Queen Elizabeth University Hospital; 🇬🇧 Glasgow, United Kingdom