Cardiac Arrhythmias and Sudden Death in Patients Affected With Laminopathies

April 5, 2016 updated by: Georgia Sarquella Brugada, MD PhD, Hospital Sant Joan de Deu

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Barcelona
      • Esplugues, Barcelona, Spain, 08950
        • Recruiting
        • Pediatric Arrhythmia Unit, Hospital Sant Joan de Déu
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EPS and ECG holter monitor
Electrophysiological study (EPS) and ECG holter monitor implantation
Device: Electrophysiological Study and ECG holter monitor
Electrophysiological Study and ECG holter monitor implantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ejection Fraction (%)
Time Frame: 4 years

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
Strain (%)
Time Frame: 4 years
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
Strain Rate (%/s)
Time Frame: 4 years
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
Presence of arrhythmias (yes/no)
Time Frame: 3 years
By inserting the Holter monitoring system, presence or absence of arrhythmias can be assessed.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Sant Joan de Deu

Collaborators

Marcio Andres Foundation

Investigators

  • Principal Investigator: Georgia Sarquella-Brugada, MD, PhD, Hospital Sant Joan de Déu

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2015

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

September 1, 2019

Study Registration Dates

First Submitted

October 26, 2015

First Submitted That Met QC Criteria

November 7, 2015

First Posted (Estimate)

November 10, 2015

Study Record Updates

Last Update Posted (Estimate)

April 6, 2016

Last Update Submitted That Met QC Criteria

April 5, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CARDIO-2015-01 LMNA

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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