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Refractory Localization-related EpilepsyNCT02207673

A New Method for Delineation of Epileptic Brian Tissue During Epilepsy Surgery (The HFO Study)

A study testing Tailoring of the resection based on biomarker in aEcoG during epilepsy surgery in people with Refractory Localization-related Epilepsy, run by UMC Utrecht at 2 sites in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Any age
Conditions the study is for
Refractory Localization-related Epilepsy
What is being tested?
Tailoring of the resection based on biomarker in aEcoG during epilepsy surgery
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
2 sitesNetherlands
Study dates
Nov 2014to Jun 2021
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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.

Trial locations and contacts

2 sites in 1 country.

Netherlands2 sites

  • VU University medical center

    Amsterdam, 1081 HV

  • University Medical Center Utrecht

    Utrecht, 3584 CG

Other trials in Netherlands

About this study

Official title: Intra-operative Detection and Localisation of High Frequency Oscillations in the ECoG to Guide Epilepsy Surgery

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.

Read more

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).

Being tested
Tailoring of the resection based on biomarker in aEcoG during epilepsy surgery
Keywords
epilepsy surgery, biomarker, high frequency oscillations (HFOs), acute electrocorticography (aECoG)
Medical subject headings
Epilepsies, Partial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tailoring of the resection based on biomarker in aEcoG during epilepsy surgeryProcedure or surgery

Study groups in NCT02207673
Study groupRoleWhat they receive
Spikes as biomarkerActive comparatorIn arm " spikes" the resection of epileptogenic tissue is guided by epileptiform spikes in the aECoG (current standard). (Independent of the randomisation ictiform spike patterns will always be resected.)
Receives: Procedure: Tailoring of the resection based on biomarker in aEcoG during epilepsy surgery
HFOs as biomarkerExperimentalIn arm "HFOs" resection of epileptogenic tissue is guided by HFOs in the aECoG (new). (Independent of the randomisation ictiform spike patterns will always be resected.)
Receives: Procedure: Tailoring of the resection based on biomarker in aEcoG during epilepsy surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Post-surgical outcome

    To simplify analysis outcome scores will be dichotomized in two categories, total seizure freedom (Engel Ia+Ib) versus seizure recurrence (Engel Ic-IV).To enable interim analysis of the outcome in terms of seizures, we will determine preliminary post-surgical outcomes at 6-8 weeks and 6 months. A final outcome will be determined after 12 months. This will require the patients to fill in an additional short questionnaire on their seizure frequency at pre-surgical baseline (after singing informed consent), at 6-8 weeks, 6 and 12 months post- operatively (by telephone/email).

    So called 'running down' seizures, seizures that occur in the first 2 weeks after surgery are not considered as seizure recurrence.

    Measured: 12 months after surgery

Secondary outcomes (6)

  1. Volume of resected tissue

    With HFOs being a more specific and sensitive biomarker for epileptogenic tissue than spikes, potentially the resection size could become smaller or larger. Therefore, the volume of resected tissue (in cm3) is investigated as a secondary parameter. The amount of resected tissue is determined by voxel-based volumetrics of the pre- and post-surgical MRI using Curryscan7 Neuroimaging Suite (Compumedics Neuroscan, Hamburg, GER).

    Measured: 3 months after surgery a post-resection MRI is made

  2. Neurological deficits

    Neurological changes (e.g visual field defects, hemiparesis, word finding difficulties) can be divided into pre-existing, aggravated /improved, or new deficits, and can be anticipated or unexpected. The neurological changes and severity will be assessed by the doctor in charge/neurologist before surgery and prior to discharge out of hospital. In case of deficits they will be classified/quantified using the National Institutes of Health Stroke Scale (NIHSS) . This will be repeated by the doctor in charge/neurologist/neurosurgeon after 6 months and 12 months in case of initial neurological changes/deficits. The patient's total NIHSS scores is calculated by summation of all scores (NIHSS score range 0-42). A difference of 1 point on the NIHSS scale between 2 tests is considered clinical relevant in our population of epilepsy patients.

    Measured: baseline + post operative before discharge, 6-8 weeks, 6 and 12 months

  3. Cognitive functioning

    Comparison of test results of pre- and post-operative (6 or 12 months) neurophysiological 695 investigation (NPO). This routine neurophysiological investigation includes testing of IQ (verbal and performal), working memory and processing speed. All tests conform to the age of the patient, but report on the same domains. Per domain individual patients' results will be dichotomized into negative/no/positive change compared to pre-surgical performance. This enables comparison of all patients, independent from age, at group level.

    Measured: pre- vs. post surgery (6 or 12 months)

  4. Health related Quality of life (HRQOL)

    Health related quality of life (HRQOL; QUOLI89 for adults and an age adapted comparable list for children) will be determined pre-and post-operatively (6 or 12 months) during routine neurophysiological investigation (NPO). Interim assessment of HRQol will be enabled by a visual analogue scale (VAS) on overall self-perceived health (including their epilepsy) included in the baseline and follow-up questionnaire. This VAS scale is also part of the HRQoL tests.

    Measured: pre- vs. post-operative (6 or 12 months)

  5. Procedure duration

    Post-hoc analysis of duration of surgery (minutes) and aECoG recording time (minutes).

    Measured: intraoperative

  6. Complications related to study procedures

    Complications related to study procedures Accounts are kept of the number of (post-)operative complications, such as bleeding, infection, unexpected or aggravated neurological deficits. These events will also be reported as (Serious) Adverse Events ((S)AEs). Monitoring and interim analysis by the DMC will be based on these numbers , as well as end-point determination.

    Measured: during 12 months of post-opertive follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2014 (estimated)
  2. Study startNov 2014
  3. Primary completionFeb 2021 (estimated)
  4. Study completionJun 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02207673
Sponsor's protocol ID
NL44527.041.13
Other IDs
13-389, 2012-4
Status last verified
Nov 2020
First submitted
31 Jul 2014
Last updated
4 Nov 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 26399310

  • 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.

    PubMed 36270309

Questions about this trial

What is this clinical trial studying?

A study testing Tailoring of the resection based on biomarker in aEcoG during epilepsy surgery in people with Refractory Localization-related Epilepsy, run by UMC Utrecht at 2 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 4 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Post-surgical outcome (time frame: 12 months after surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02207673, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2020.

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