Biomarkers in SCOTland CardiomyopatHy Registry (Bio-SCOTCH)

Cardiomyopathies Clinical Trial

Official title:

Biomarkers in SCOTland CardiomyopatHy Registry

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06446271
• Other study ID #: GN23CA296
• Status: Not yet recruiting
• Start date: June 11, 2024
• Est. completion date: March 19, 2027

Study information

• Verified date: May 2024
• Source: NHS Greater Glasgow and Clyde
• Contact: Caroline J Coats, MBBS, PhD
• Phone: 0141 451 6121
• Email: Caroline.Coats[@]glasgow.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 750
• Est. completion date: March 19, 2027
• Est. primary completion date: March 19, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cardiomyopathies
• Genetic Predisposition
• Genetic Predisposition to Disease

Intervention

Diagnostic Test:
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
NHS Greater Glasgow and Clyde	Roche Diagnostics GmbH, University of Glasgow

Outcome

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