Cardiac Arrhythmias in Dravet Syndrome

NCT02415686 | Completed

• 1 other identifier: NL48765.058.15
• Study Type: observational
• Target: 59
• Locations: 3 countries
• Sites: 3

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.

Conditions

Epilepsy

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Ictal QT lengthening or shortening

  We will record heart rate patterns during seizures with miniaturized wearable EKG-monitors for 2 periods of 10 days

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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: 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Stichting Epilepsie Instellingen Nederland: lead
• Epilepsiefonds: collaborator

Study Sites (3)

Universität Bonn

Bonn, North Rhine-Westphalia, 53113, Germany

Location

Stichting Epilepsie Instellingen Nederland (SEIN)

Heemstede, Achterweg 5, 2103 SW, Netherlands

Location

Great Ormond Street Hospital

London, South East, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Epilepsy; Epilepsies, Myoclonic; Sudden Unexpected Death in Epilepsy; Arrhythmias, Cardiac

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases

Study Officials

• Roland Thijs, Dr.

  Stichting Epilepsie Instellingen Nederland (S.E.I.N.)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2015
• First Posted: April 14, 2015
• Study Start: June 1, 2015
• Primary Completion: August 29, 2018
• Study Completion: August 29, 2018
• Last Updated: September 7, 2018

Record last verified: 2017-11

Locations

GB (1); NL (1); DE (1)