Clinical trial NCT02954107: Longitudinal Early Epilepsy Study
Official title: Longitudinal Early Epilepsy Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Absence Epilepsy
Epilepsy, Absence
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Epilepsiecentrum Kempenhaeghe
First posted: 2016-11-03
Enrollment: 60
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1. Children aged 6-12 years of age primarily presenting with episodes of brief loss of consciousness (absences) in an otherwise normal child in the previous 2 years. With an EEG showing 3 Hz (2.5-4.5 Hz) generalized rhythmic spike-and-wave complexes with a discharge duration of at least 3 seconds on a present or former EEG.
2. Overall healthy children aged 6-12 years of age following a regular school without major problems.

Brief summary: This longitudinal study will focus on the cognitive and brain development of children with absence epilepsy. In addition, the investigators aim to identify prognostic factors for cognitive deterioration and/or poor seizure control in these children.

Detailed description: The aim is to study the cognitive and brain development of children with absence epilepsy. In addition, this study aims to identify prognostic factors for cognitive deterioration and/or poor seizure control.

Objective:

1. To study the development of cognition in children with absence epilepsy and the functional brain organization over time.
2. To find prognostic factors in terms of clinical, 24h-video-EEG or/and MRI characteristics for cognitive deterioration and/or poor seizure control in patients with absence epilepsy.

Study design:

2 year prospective longitudinal, controlled, comparative, clinical, follow up.

Study population:

60 children with recently diagnosed (\<2 years) absence epilepsy, aged 6 to 12 years. In addition, this study includes a control group of 15 age and gender matched healthy volunteers.

Main study parameters/endpoints:

Endpoints are the development of clinical parameters (semiology, 24h-video-EEG and seizure control), neuropsychological/behavioural outcomes, structural/functional MRI parameters, and educational performance.

Eligibility criteria: Inclusion Criteria:

1. Primarily presented with daily occurring episodes of brief loss of consciousness (absences) in an otherwise normal child in the previous 2 years.
2. An EEG showing 3 Hz (2.5-4.5 Hz) generalized rhythmic spike-and-wave complexes with a discharge duration of at least 3 seconds on a present or former EEG(58).
3. Early absence epilepsy , defined as a confirmed diagnosis or seizures within 2 years.
4. Aged 6-12 years
5. Permitted accompanying factors:

   * A few generalized tonic-clonic seizures (assessed individually according to International League Against Epilepsy \[ILAE\] statements;
   * Mild myoclonic eye(lid) movements
   * Co-morbidities: Attention deficiency/concentration disorders, autism, dyslexia and anxiety. These do not form exclusion criteria as this is frequently seen in children with absence seizures and it might be uncertain if the co-morbidity is a manifestation of the absence epilepsy.

Exclusion Criteria:

* A potential subject (both for the control and patient group) who meets any of the following criteria will be excluded from participation in this study:

  * A diagnosis according to ILAE criteria of the following epilepsy syndromes: Juvenile Absence Epilepsy; Eyelid myoclonia with absences; Dravet syndrome; Epilepsy with myoclonic-atonic seizures; Epilepsy with Myoclonic Absences; Lennox-Gastaut syndrome; Frontal Lobe Epilepsy or other focal epilepsy.
  * A confirmed diagnosis of epilepsy/seizures for more than 2 years (59).
  * Recent hospitalizations in the last months or a history which might limit participation in or completion of the study protocol.
  * Behavioural characteristics which might hamper the gathering of useful MRI data.
  * Intellectual disability or other diseases/causes that may underlie cognitive impairment (i.e. neurodegenerative diseases).
  * History of major head trauma or head/brain surgery.
  * MRI lesions on (previous) structural brain MRI- or CT-scans or symptomatic epilepsies (e.g. epilepsy related to tumours, vascular abnormalities, congenital dysgenesia).
  * MRI contra-indications: claustrophobia, anxiety for an MRI scan, or presence of metallic objects (e.g. prostheses, pacemakers, metal clips on blood vessels, metal parts in the eye). Dental braces are no exclusion criterion for absence patients.
  * Regularly using drugs of abuse (asked during screening session).
  * Parents or participants (aged≥12 years) not willing to provide informed consent.
  * Parents or participants (aged≥12 years) who do not want to get informed whenever structural abnormalities are found during imaging.

Primary outcomes:
measure: Change of multimodal MRI parameters on brain connectivity
timeFrame: Baseline; first year; second year
measure: Change of cognition measured by a battery of neuropsychological tests
timeFrame: Baseline; first year; second year
measure: Time in months since start of medication till seizure control is attained, as assessed by anamnesis and a confirmatory routine-EEG.
timeFrame: Within 2 years
Secondary outcomes:
measure: Age in months at which seizures began (age of onset) assessed by interview at the baseline measurment
timeFrame: Baseline
measure: Seizure semiology assessed by anamnesis and video-EEG
timeFrame: Baseline; first year; second year
measure: Epileptiform activity assessed by a 24h-EEG
timeFrame: Baseline; first year; second year
Other outcomes:
Locations:
city: Heeze
country: Netherlands
facility: Kempenhaeghe
state: Limburg
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
Study officials:
affiliation: Maastricht University Medical Center
name: Johan SH Vles, MD, PHD
role: STUDY_DIRECTOR
References: