Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02207673
Recruitment Status : Unknown
Verified May 2016 by G.J.M. Zijlmans, UMC Utrecht.
Recruitment status was:  Recruiting
First Posted : August 4, 2014
Last Update Posted : May 12, 2016
Sponsor:
Collaborator:
Rudolf Magnus Institute – University of Utrecht
Information provided by (Responsible Party):
G.J.M. Zijlmans, UMC Utrecht

Tracking Information
First Submitted Date  ICMJE July 31, 2014
First Posted Date  ICMJE August 4, 2014
Last Update Posted Date May 12, 2016
Study Start Date  ICMJE November 2014
Estimated Primary Completion Date April 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 1, 2014)
Post-surgical outcome [ Time Frame: 12 months after surgery ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02207673 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2014)
  • Volume of resected tissue [ Time Frame: 3 months after surgery a post-resection MRI is made ]
    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).
  • Neurological deficits [ Time Frame: baseline + post operative before discharge, 6-8 weeks, 6 and 12 months ]
    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.
  • Cognitive functioning [ Time Frame: pre- vs. post surgery (6 or 12 months) ]
    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.
  • Health related Quality of life (HRQOL) [ Time Frame: pre- vs. post-operative (6 or 12 months) ]
    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.
  • Procedure duration [ Time Frame: intraoperative ]
    Post-hoc analysis of duration of surgery (minutes) and aECoG recording time (minutes).
  • Complications related to study procedures [ Time Frame: during 12 months of post-opertive follow-up ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A New Method for Delineation of Epileptic Brian Tissue During Epilepsy Surgery (The HFO Study)
Official Title  ICMJE Intra-operative Detection and Localisation of High Frequency Oscillations in the ECoG to Guide Epilepsy Surgery
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).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Refractory Localization-related Epilepsy
Intervention  ICMJE Procedure: Tailoring of the resection based on biomarker in aEcoG during epilepsy surgery
Study Arms  ICMJE
  • Active Comparator: Spikes as biomarker
    In 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.)
    Intervention: Procedure: Tailoring of the resection based on biomarker in aEcoG during epilepsy surgery
  • Experimental: HFOs as biomarker
    In 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.)
    Intervention: Procedure: Tailoring of the resection based on biomarker in aEcoG during epilepsy surgery
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: August 1, 2014)
78
Original Estimated Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date April 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02207673
Other Study ID Numbers  ICMJE NL44527.041.13
13-389 ( Other Identifier: Ethical review board UMC Utrecht )
2012-4 ( Other Grant/Funding Number: Dutch Epilepsy Foundation )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party G.J.M. Zijlmans, UMC Utrecht
Study Sponsor  ICMJE UMC Utrecht
Collaborators  ICMJE Rudolf Magnus Institute – University of Utrecht
Investigators  ICMJE
Principal Investigator: Maeike Zijlmans, MD, PhD University Medical Center Utrecht, the Netherlands
Study Director: Maryse van 't Klooster, MSc. University Medical Center Utrecht, the Netherlands
PRS Account UMC Utrecht
Verification Date May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP