Clinical trial NCT02601066: Cardiac Arrhythmias and Sudden Death in Patients Affected With Laminopathies
Official title: Identification of Predictors of Cardiac Arrhythmias and Sudden Death in Pediatric Patients Affected With Laminopathies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cardiomyopathy Associated With Myopathy and Sudden Death
Keywords: LMNA
Sudden Death
Neuromuscular
Lead sponsor: Hospital Sant Joan de Deu
Sponsor class: OTHER
Collaborators: name: Marcio Andres Foundation
First posted: 2015-11-10
Enrollment: 40
Sex: ALL
Minimum age (years): 1
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Ejection Fraction (%)
timeFrame: 4 years
measure: Strain (%)
timeFrame: 4 years
measure: Strain Rate (%/s)
timeFrame: 4 years
measure: Presence of arrhythmias (yes/no)
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Esplugues
country: Spain
facility: Pediatric Arrhythmia Unit, Hospital Sant Joan de Déu
state: Barcelona
Study officials:
affiliation: Hospital Sant Joan de Deu
name: Georgia Sarquella-Brugada, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: