The Deep Phenotype of Lamin A/C Cardiomyopathy

Lamin A/C Gene Mutation Clinical Trial

Official title:

The Deep Phenotype of Lamin A/C Cardiomyopathy - A Proof-of-principle Relax-omic Pipeline

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03860454
• Other study ID #: 16/0661
• Secondary ID: 17/LO/0167
• Status: Recruiting
• Start date: March 7, 2019
• Est. completion date: February 1, 2025

Study information

• Verified date: October 2019
• Source: University College, London
• Contact: Prof. James C Moon, Professor of Cardiology
• Phone: +44 (0)2034566020
• Email: j.moon[@]ucl.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: February 1, 2025
• Est. primary completion date: February 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Dilated Cardiomyopathy, Familial
• Lamin A/C Gene Mutation

Locations

Country	Name	City	State
United Kingdom	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	Royal Free Hospital NHS Trust (RFH)	London
United Kingdom	University College London Hospital NHS Trust (UCLH)	London
United Kingdom	Papworth Hopsital NHS Trust	Papworth Everard

Sponsors (3)

Lead Sponsor	Collaborator
University College, London	Barts Cardiovascular registry, NIHR Rare Diseases Translational Research Collaboration

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Positive and negative predictive value of imaging-omics test for diagnosing LMNA-related heart muscle disease.		3-4 years