The Deep Phenotype of Lamin A/C Cardiomyopathy

Recruiting

• Conditions: Lamin A/C Gene Mutation; Dilated Cardiomyopathy, Familial

• Registration Number: NCT03860454
• Lead Sponsor: University College, London

Brief Summary

This study seeks to discover clinically useful tests to improve the diagnosis of a rare and serious heart muscle disease caused by mutations in a gene called 'Lamin'.

Patients born with lamin gene mutations have apparently healthy hearts initially, they begin experiencing symptoms in their twenties or thirties, and by age 45 the majority have undergone a heart transplant, experienced a major cardiac complication, or have died. Sudden heart rhythm abnormalities are a major cause of sudden death so earlier diagnosis can save lives by enabling timely treatment or implantation of specialised pacemakers (defibrillators). In clinical practice, diagnosis of lamin heart disease currently relies on the genetic test. Very little is known about the detailed imaging features of the hearts of patients with lamin heart disease although advanced echocardiography and cardiac MRI now offer the opportunity to study the health of the heart without the need for radiation.

Detailed Description

* Research participants will undergo resting 12-lead ECG, 24-hour ambulatory ECG, baseline echocardiography, exercise echocardiography, cardiac MRI scan.

* Blood samples will be collected in all participants from both centers for immediate laboratory testing.

* Blood and urine samples will be collected in all participants and used for metabolomic, proteomic and lipidomic profiling and for targeted metabolite and enzyme analysis.

* Blood samples will be collected in all participants for future gene code analysis (DNA / RNA).

Study Timeline

• Study First Submitted: 2019-01-15
• Study First Submitted QC: 2019-03-01
• Study First Posted: 2019-03-04
• Study Start: 2019-03-07
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-15
• Last Update Posted: 2019-10-16
• Primary Completion: 2025-02-01
• Study Completion: 2025-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• LMNA+ cases with pathogenic LMNA mutations for LMNA+ and heart myocardial samples from the explanted hearts of LMNA+ patients who are scheduled to undergo clinically indicated heart transplantation at the Papworth Hospital NHS Trust.
• DCMWT cases: patients with heart muscle failure but with wild-type lamin gene. Heart myocardial samples from the explanted hearts of DCMWT patients who are scheduled to undergo clinically indicated heart transplantation at the Papworth Hospital NHS Trust.
• HV (controls): matched to cases.

Exclusion Criteria

• Needle-phobia that would preclude blood-letting
• Participants unwilling to consent
• Patients that have a conventional contraindication for cardiac magnetic resonance imaging (MRI).
• Patients that have had a blood transfusion within the last month and patients having haemodialysis will be excluded.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Positive and negative predictive value of imaging-omics test for diagnosing LMNA-related heart muscle disease.	3-4 years

Trial Locations

Locations (6)

University Hospital Birmingham (UHB); 🇬🇧 Birmingham, United Kingdom

Barts Heart Center, St Bartholomew's Hospital NHS Trust; 🇬🇧 London, United Kingdom

Royal Brompton Hospital NHS Trust (RBHT); 🇬🇧 London, United Kingdom

University College London Hospital NHS Trust (UCLH); 🇬🇧 London, United Kingdom

Royal Free Hospital NHS Trust (RFH); 🇬🇧 London, United Kingdom

Papworth Hopsital NHS Trust; 🇬🇧 Papworth Everard, United Kingdom