Cardiac Arrhythmias in Dravet Syndrome

Epilepsy Clinical Trial

Official title:

Cardiac Arrhythmias in Dravet Syndrome: an Observational, International, Multicentre Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02415686
• Other study ID #: NL48765.058.15
• Status: Completed
• Start date: June 2015
• Est. completion date: August 29, 2018

Study information

• Verified date: November 2017
• Source: Stichting Epilepsie Instellingen Nederland
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

SUMMARY

Rationale:

People with Dravet Syndrome (DS), a rare epilepsy syndrome, have a high risk of Sudden Unexpected Death in Epilepsy (SUDEP). Mouse models indicated that the responsible sodium channel mutation (SCN1A) not only alters cortical excitability but also increases the propensity to arrhythmias. Little is known yet about the prevalence of seizure-induced arrhythmias in human DS subjects.

Objective:

To assess the prevalence of cardiac arrhythmias in DS and to compare the prevalence of cardiac arrhythmias between DS subjects and subjects with other types of epilepsy.

Study design:

Observational study.

Study population:

Subjects with Dravet syndrome and a known pathogenic SCN1A mutation, seizure frequency ≥ 1/week (all seizure types except for absences or myoclonias), age ≥ 6 years and no signs of self-harm. Each case will be matched to two historical controls (age +/- 5 years) from the EEG databases of the participating centres. Only those controls with two or more recorded seizures will be matched to the cases.

Intervention:

Main study parameters/endpoints:

Ictal asystole Ictal bradycardia Ictal QT-shortening/lengthening

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Participation does not carry risks. The sensor is wearable and miniaturised, thus minimising discomfort. If this nevertheless may occur, the study can be terminated. This study provides specific tools to investigate the seizure-related heart rate response. Subjects may thus benefit from participation by identification of otherwise unknown arrhythmias. The rationale of the study (the high SUDEP risk and the evidence in animal studies for arrhythmic cause of sudden death) specifically applies to DS, a rare epileptic syndrome including minors and incapacitated persons. The investigators believe that the lack of risks, the potential diagnostic benefit, the minimal intervention with novel and wearable sensors and the possibility to terminate the study in case of discomfort, justifies the study in this patient group.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: August 29, 2018
• Est. primary completion date: August 29, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

Criteria:

Cases must meet all of the following criteria:

1. DS with a known pathogenic SCN1A mutation

2. seizure frequency = 1/week (all seizure types expect for absences or myoclonias)

3. no self-harm

4. age = 6 years

Each case will be matched to two historical controls (age +/- 5 years). Controls will meet the following criteria:

1. definite diagnosis of epilepsy

2. no clinical suspicion of DS

3. at least two seizures recorded (all seizure types expect for absences or myoclonias) during video-EEG registration.

4. age = 6 years

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Epilepsies, Myoclonic
• Epilepsy

Locations

Country	Name	City	State
Germany	Universität Bonn	Bonn	North Rhine-Westphalia
Netherlands	Stichting Epilepsie Instellingen Nederland (SEIN)	Heemstede	Achterweg 5
United Kingdom	Great Ormond Street Hospital	London	South East

Sponsors (2)

Lead Sponsor	Collaborator
Stichting Epilepsie Instellingen Nederland	Epilepsiefonds

Countries where clinical trial is conducted

Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ictal asystole (sinus arrest = 3 s) or ictal bradycardia (< 2nd heart rate percentile for age)		We will record heart rate patterns during seizures with miniaturized wearable EKG-monitors for 2 periods of 10 days
Secondary	Ictal QT lengthening or shortening		We will record heart rate patterns during seizures with miniaturized wearable EKG-monitors for 2 periods of 10 days