Cardiac Arrhythmias and Sudden Death in Patients Affected With Laminopathies

Cardiomyopathy Associated With Myopathy and Sudden Death Clinical Trial

Official title:

Identification of Predictors of Cardiac Arrhythmias and Sudden Death in Pediatric Patients Affected With Laminopathies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02601066
• Other study ID #: CARDIO-2015-01 LMNA
• Status: Recruiting
• Phase: N/A
• First received: October 26, 2015
• Last updated: April 5, 2016
• Start date: September 2015
• Est. completion date: September 2019

Study information

• Verified date: April 2016
• Source: Hospital Sant Joan de Deu
• Contact: Georgia Sarquella-Brugada, MD, PhD
• Email: georgia[@]brugada.org
• Is FDA regulated: No
• Health authority: Spain: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This research study includes patients ages 1 to 25 years old with Lamin A/C related muscular dystrophy (LMNA-MD). The goal of this study is to evaluate how the heart is affected in children and teens with LMNA-MD. The evaluation includes an echocardiogram, an electrocardiogram, an electrophysiological study and the implantation of a subcutaneous ECG holter monitor.

Description:

The LMNA related muscular dystrophies are monogenic progressive neuromuscular disorders. Affected pediatric patients can present at birth or in childhood and are classified as either congenital muscular dystrophy (LMNA-CMD), congenital onset Limb-girdle muscular dystrophy type 1B (LGMD1B) or childhood onset Emery Dreifuss muscular dystrophy (EDMD). These distinct clinical presentations all involve variants in the LMNA gene and can be distinguished by method of inheritance. Those with LMNA-CMD have new mutations in the LMNA gene not carried by either parent, while those with LGMD1B and EDMD will have a parent who may or not have symptoms with the same variant (change in the LMNA gene). There is no current cure or treatment for LMNA-MD.

While heart involvement has been studied for the adult forms of LMNA muscular dystrophy. These studies have identified an increased risk for arrhythmia (abnormal heart rhythms), conduction defects, cardiomyopathy and sudden cardiac death. To date there has been no study evaluating the age of onset of heart involvement, the type of heart involvement, the rate of heart disease progression and the risk of sudden cardiac death in children affected with LMNA-MD. The investigators' research aims to evaluate heart involvement in children and teens affected by LMNA-MD.

This is a prospective interventional natural history study. The intervention consists of 3 steps: 1) High complexity echocardiography, 2) Electrophysiological Study, 3) subcutaneous ECG holter monitor implantation.

The duration of the active protocol will last 3 years. Potential subjects will be identified through the Spanish muscular dystrophy network and the Congenital Muscle Disease International Registry. The study will involve one on-site visit at Sant Joan de Déu Hospital in Barcelona, Spain; and a yearly follow-up that will be arrange individually (either a second visit to Barcelona or doctors will travel to see the patient).

At Visit 1, subjects will have their baseline assessments, including an echocardiogram, an electrocardiogram, a electrophysiological study and medication review and the subcutaneous ECG holter monitor implantation.

The second study visit will occur 12-14 months after the first study visit. Remote monitoring through the holter device will continue for 36 months after placement of the device.

For those individuals traveling from outside Spain, travel arrangements will be eased by Andres Marcio Foundation

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 25 Years

Eligibility

Inclusion Criteria:

• Age of onset of muscle weakness between birth and 5 years of age

• Confirmed LMNA related muscular dystrophy by gene mutation AND clinical history

Exclusion Criteria:

• ny neuromuscular disorder other than LMNA related muscular dystrophy

• unable to comply with an echocardiogram or an electrophysiologic study

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Cardiomyopathies
• Cardiomyopathy Associated With Myopathy and Sudden Death
• Death
• Death, Sudden

Intervention

Device:
• Electrophysiological Study and ECG holter monitor
Electrophysiological Study and ECG holter monitor implantation

Locations

Country	Name	City	State
Spain	Pediatric Arrhythmia Unit, Hospital Sant Joan de Déu	Esplugues	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Sant Joan de Deu	Marcio Andres Foundation

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ejection Fraction (%)	Heart involvement has been studies for the adult forms of LMNA muscular dystrophy. These studies have identified an increased risk for arrhythmia (abnormal heart rhythms), conduction defects, cardiomyopathy and sudden cardiac death. To date there has been no study evaluating the age of onset of heart involvement, the type of heart involvement, the rate of heart disease progression and the risk of sudden cardiac death in children affected with LMNA-MD.; Outcome Measures: Ejection Fraction%, Strain Rate, time of arrhythmia in 24 hours, type of arrhythmia.	4 years	No
Primary	Strain (%)	Myocardial deformation (strain) can be obtained based on Tissue Doppler Imaging (TDI) or on bidimensional images (speckle tracking). TDI allows better time definition and can be also used in case of poor echocardiographic windows. Analyses from bidimensional images allow assessment of radial and circumferencial strain, as well as apical and basal rotation, needed to calculate ventricular torsion. Normal values of longitudinal LV deformation are between -20 to -25 %.	4 years	No
Primary	Strain Rate (%/s)	Rate of myocardial deformation in time. Diastolic myocardial deformation can be assessed more clearly in this way. Normal values of longitudinal LV deformation are 1 - 1.5/s or higher.	4 years	No
Primary	Presence of arrhythmias (yes/no)	By inserting the Holter monitoring system, presence or absence of arrhythmias can be assessed.	3 years	No