Cardiac Arrhythmias in Dravet Syndrome

• ClinicalTrials.gov Identifier: NCT02415686
• Recruitment Status: Completed
• First Posted: April 14, 2015
• Last Update Posted: September 7, 2018
• Sponsor: Stichting Epilepsie Instellingen Nederland
• Collaborator: Epilepsiefonds
• Information provided by (Responsible Party): Stichting Epilepsie Instellingen Nederland

Study Description

Brief 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:

Not applicable

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.

Condition or disease
Epilepsy

Study Design

• Study Type: Observational
• Actual Enrollment: 59 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Cardiac Arrhythmias in Dravet Syndrome: an Observational, International, Multicentre Study
• Actual Study Start Date: June 2015
• Actual Primary Completion Date: August 29, 2018
• Actual Study Completion Date: August 29, 2018

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Ictal asystole (sinus arrest ≥ 3 s) or ictal bradycardia (< 2nd heart rate percentile for age) [ Time Frame: We will record heart rate patterns during seizures with miniaturized wearable EKG-monitors for 2 periods of 10 days ]

Secondary Outcome Measures :

1. Ictal QT lengthening or shortening [ Time Frame: We will record heart rate patterns during seizures with miniaturized wearable EKG-monitors for 2 periods of 10 days ]

Eligibility Criteria

• Ages Eligible for Study: 6 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

the Netherlands (coordinating centre: SEIN). Procedure: The UMCU Medical Genetics department is the key referral centre in the Netherlands for DS (Brilstra, UMCU). Cases will be recruited from the UMCU database. Prior to inclusion, a panel (Gunning, Brilstra, Thijs) will review clinical data to ensure diagnostic consistency.

Additional DS subjects will be recruited from the local DS databases at Universität Bonn (25 subjects; 4 adults; local coordinator R Surges) and UCL (100 subjects; 15 adults; local coordinator S Sisodiya).

We will select historical controls (subjects with epilepsy without DS) from the video-EEG databases of the participating centres.

Criteria

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

Contacts and Locations

Locations

Germany

Universität Bonn

Bonn, North Rhine-Westphalia, Germany, 53113

Netherlands

Stichting Epilepsie Instellingen Nederland (SEIN)

Heemstede, Achterweg 5, Netherlands, 2103 SW

United Kingdom

Great Ormond Street Hospital

London, South East, United Kingdom, WC1N 3JH

Sponsors and Collaborators

Stichting Epilepsie Instellingen Nederland

Epilepsiefonds

Investigators

• Principal Investigator: Roland Thijs, Dr.; Stichting Epilepsie Instellingen Nederland (S.E.I.N.)

More Information

• Responsible Party: Stichting Epilepsie Instellingen Nederland
• ClinicalTrials.gov Identifier: NCT02415686
• Other Study ID Numbers: NL48765.058.15
• First Posted: April 14, 2015
• Last Update Posted: September 7, 2018
• Last Verified: November 2017

Keywords provided by Stichting Epilepsie Instellingen Nederland:

Dravet syndrome; Sudden Unexpected Death in Epilepsy (SUDEP); Arrhythmias

Additional relevant MeSH terms:

Epilepsy; Epilepsies, Myoclonic; Arrhythmias, Cardiac; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Heart Diseases; Cardiovascular Diseases; Epilepsy, Generalized; Epileptic Syndromes