Biomarkers in SCOTland CardiomyopatHy Registry (Bio-SCOTCH)

Biomarkers in SCOTland CardiomyopatHy Registry

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiomyopathies; Genetic Predisposition; Cardiomyopathy, Primary
• Intervention / Treatment: Diagnostic test: Plasma biomarker levels

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 Type: Observational
• Enrollment (Estimated): 750

Contacts and Locations

• Study Contact: Name: Caroline J Coats, MBBS, PhD; Phone Number: 0141 451 6121; Email: Caroline.Coats@glasgow.ac.uk
• Study Contact Backup: Name: Rachel C Myles, MBBS, PhD; Phone Number: 0141 451 6121; Email: Rachel.Myles@glasgow.ac.uk

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Recruiting
    • Queen Elizabeth University Hospital
    • Contact: Caroline J Coats, MBBS, PhD; Email: Caroline.Coats@glasgow.ac.uk
    • Contact: Fraser C Goldie, MBChB; Email: Fraser.Goldie@glasgow.ac.uk
    • Principal Investigator: Caroline J Coats, MBBS, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

People with a personal or family history of TTN, LMNA, MYBPC3, DSP, or FLNC gene variant who have been referred to the West of Scotland Inherited Cardiac Conditions Service clinic.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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	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.; Other Names: Echocardiogram; Electrocardiogram; Cardiac magnetic resonance imaging; 24-hour Holter monitor; Questionnaires (Kansas City Cardiomyopathy Questionnaire & General Practice Physical Activity Questionnaire); Urine biomarker levels
Gene negative controls (family history of TTN, MYBPC3, LMNA, FLNC or DSP gene variant); Expected recruitment of 50 patients.	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.; Other Names: Echocardiogram; Electrocardiogram; Cardiac magnetic resonance imaging; 24-hour Holter monitor; Questionnaires (Kansas City Cardiomyopathy Questionnaire & General Practice Physical Activity Questionnaire); Urine biomarker levels

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker correlation	Correlation of biomarkers with cardiac imaging measures of inflammation and myocardial fibrosis in genetic cardiomyopathies.	3 years
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
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
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

Collaborators and Investigators

• Sponsor: NHS Greater Glasgow and Clyde
• Collaborators: University of Glasgow; Roche Diagnostics GmbH

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2024
• Primary Completion (Estimated): March 19, 2027
• Study Completion (Estimated): March 19, 2027

Study Registration Dates

• First Submitted: May 31, 2024
• First Submitted That Met QC Criteria: May 31, 2024
• First Posted (Actual): June 6, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 1, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Genetic; Cardiomyopathy; Biomarkers
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease Attributes; Disease Susceptibility; Cardiomyopathies; Genetic Predisposition to Disease
• Other Study ID Numbers: GN23CA296

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No