Clinical trial NCT02207673: A New Method for Delineation of Epileptic Brian Tissue During Epilepsy Surgery (The HFO Study)
Official title: Intra-operative Detection and Localisation of High Frequency Oscillations in the ECoG to Guide Epilepsy Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Refractory Localization-related Epilepsy
Keywords: epilepsy surgery
biomarker
high frequency oscillations (HFOs)
acute electrocorticography (aECoG)
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Rudolf Magnus Institute - University of Utrecht
First posted: 2014-08-04
Enrollment: 78
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Epilepsy occurs in 0.5-0.7% of the population, of which 25% are children. 30% Of patients with focal epilepsy do not respond well to medication and half of them are eligible for epilepsy surgery. In recent years, the importance of early epilepsy surgery has been stressed, as successful surgery may lead seizure and medication freedom and improved social and cognitive development, especially in children. The current success rate of epilepsy surgery is around 65%; During surgery intracranial electrocorticography (acute ECoG, aECoG) is recorded in some medical centers. The presence of epileptiform brian activity, spikes, identified by clinical neurophysiologists, is used to guide the neurosurgeon in the extent of the brain tissue that needs to be resected. Spikes are considered markers of the presence of epilepsy. High Frequency Oscillations (HFOs, \>80-500Hz) in the ECoG have recently been identified as a new biomarker for epileptogenic tissue. Retrospective research shows that their local presence strongly relates to the seizure onset, and removal of tissue with HFOs could predict a better surgical outcome. The area showing HFOs usually overlaps with, but is smaller than the area with spikes, and HFOs do not tend to propagate to distant sites as spikes do. The identification of HFOs is more objective than of spikes and automatic detection software exists.

A pilot study is performed to test the hypothesis : The intra-operative use of HFOs to delineate the epileptogenic cortex does not yield significantly worse outcome in seizure freedom than the current method based on spikes.

Study design is a single blinded multi-center randomized controlled trial. In two Dutch centers, the VU medical center ( Amsterdam) and University Medical Center Utrecht.

The study population (sample size 78) consists of patients of all ages with refractory epilepsy undergoing epilepsy surgery with aECoG to guide the extent of the resection.

Eligible patients are randomised, after informed consent, into group 1 (HFOs) in whom a resection guided by HFOs in the aECoG (new), or into group 2 (spikes) in whom a resection is guided by epileptiform spikes in the aECoG (current standard). Ictiform spike patterns will always be resected.

Main study endpoint is outcome after epilepsy surgery after 1 year of follow-up dichotomized in total seizure freedom (Engel Ia\&b) vs. seizure recurrence (Engel Ic-IV).


Eligibility criteria: Inclusion Criteria:

Patients of all ages with:

* Refractory Focal Epilepsy; at least ≥2 experienced seizures in the past 24 months, in spite of 2 or more different anti-epileptic drugs tried.
* Planned neurosurgery with aECoG, with the goal of tailoring the resection.
* Command of Dutch language of the patient/parents/legal representatives and capability of completing the questionnaires (by email or phone).

Exclusion Criteria:

* Patients who underwent chronic ECoG monitoring preceding epilepsy surgery (grids). This is a biased population, since the results of the extensive pre-surgical work-up as well as the results of the cECoG monitoring period are included in the final decision making regarding the resection, and a precise seizure onset zone as well as spike and HFO area are known.
* Patients with an occipital focus undergoing aECoG. Currently, it is not possible to discriminate between pathological or physiological occipital HFOs, and thus unsafe to perform HFO guided resections in patients with a presumed occipital focus.

Primary outcomes:
measure: Post-surgical outcome
timeFrame: 12 months after surgery
Secondary outcomes:
measure: Volume of resected tissue
timeFrame: 3 months after surgery a post-resection MRI is made
measure: Neurological deficits
timeFrame: baseline + post operative before discharge, 6-8 weeks, 6 and 12 months
measure: Cognitive functioning
timeFrame: pre- vs. post surgery (6 or 12 months)
measure: Health related Quality of life (HRQOL)
timeFrame: pre- vs. post-operative (6 or 12 months)
measure: Procedure duration
timeFrame: intraoperative
measure: Complications related to study procedures
timeFrame: during 12 months of post-opertive follow-up
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: VU University medical center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: University Medical Center Utrecht, the Netherlands
name: Maeike Zijlmans, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Utrecht, the Netherlands
name: Maryse van 't Klooster, MSc.
role: STUDY_DIRECTOR
References:
citation: van 't Klooster MA, Leijten FS, Huiskamp G, Ronner HE, Baayen JC, van Rijen PC, Eijkemans MJ, Braun KP, Zijlmans M; HFO study group. High frequency oscillations in the intra-operative ECoG to guide epilepsy surgery ("The HFO Trial"): study protocol for a randomized controlled trial. Trials. 2015 Sep 23;16:422. doi: 10.1186/s13063-015-0932-6.
citation: Zweiphenning W, Klooster MAV', van Klink NEC, Leijten FSS, Ferrier CH, Gebbink T, Huiskamp G, van Zandvoort MJE, van Schooneveld MMJ, Bourez M, Goemans S, Straumann S, van Rijen PC, Gosselaar PH, van Eijsden P, Otte WM, van Diessen E, Braun KPJ, Zijlmans M; HFO study group. Intraoperative electrocorticography using high-frequency oscillations or spikes to tailor epilepsy surgery in the Netherlands (the HFO trial): a randomised, single-blind, adaptive non-inferiority trial. Lancet Neurol. 2022 Nov;21(11):982-993. doi: 10.1016/S1474-4422(22)00311-8.