Condition category
Nervous System Diseases
Date applied
17/09/2020
Date assigned
25/09/2020
Last edited
02/10/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Sixty million people have epilepsy and a third of them continue to have seizures despite medication, with risks of fatality, brain damage, physical harm and psychosocial disorders. Brain surgery (neurosurgery) can control epilepsy if the responsible part of the brain is removed. We have treated 1,074 individuals with epilepsy surgery since February 1990. In optimal circumstances, 80% have no seizures for 1 year or more after surgery, and 40% never have another seizure. There may, however, be adverse effects. After surgery 30% of individuals develop increased difficulty with memory and language, and 10-20% may lose part of their field of vision.

Over the next 4 years we will implement methods to improve epilepsy surgery, streamline the pathway and so improve access:
1. Systematic analysis of seizure symptoms to better understand the areas of the brain involved in each individual. This information is combined with results of brain imaging and other brain scans and electrical recordings from the scalp and viewed in 3-dimensions.
2. Use computer-assisted analysis of brain scans to define the best locations for recording electrodes in the brain at sites thought to be giving rise to seizures, avoiding blood vessels
3. Analyse the electrical signals recorded from electrodes in the brain, integrating this with analysis of MRI and other brain scans to determine which parts need to be removed to control the epilepsy
4. Plan surgery so that there is the best chance of stopping seizures, and minimized risk of other damage

Who can participate?
Individuals aged 18-70 under consideration for epilepsy surgery for drug-resistant focal epilepsy, at National Hospital for Neurology and Neurosurgery (NHNN), who are able to appropriately consent for involvement in the research as well as for surgery itself, and has no contraindications to undergoing neurosurgery.

What does the study involve?
The study will be part of the normal investigations and assessments made by the clinical teams as a part of the assessment for epilepsy surgery, and will involve clinical assessments and brain scans before surgery, and 3-4 months after the operation to determine whether the treatment was successful.

What are the possible benefits and risks of participating?
The possible benefits include a higher likelihood of seizure freedom and a lower likelihood of developing severe neurological deficits following the surgery.

Where is the study run from?
National Hospital for Neurology and Neurosurgery (UK)

When is the study starting and how long is it expected to run for?
December 2019 to September 2024

Who is funding the study?
1. The Wellcome Trust (UK)
2. Epilepsy Research UK

Who is the main contact?
Dr Debayan Dasgupta
debayan.dasgupta@ucl.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Debayan Dasgupta

ORCID ID

Contact details

Department of Clinical and Experimental Epilepsy
UCL Institute of Neurology
Queen Square
London
WC1N 3BG
United Kingdom
+44 (0)20 8344 8613
debayan.dasgupta@ucl.ac.uk

Type

Scientific

Additional contact

Prof John Duncan

ORCID ID

Contact details

University College London Hospitals NHS Foundation Trust
250 Euston Road
London
NW1 2PG
United Kingdom
+44 (0)20 3448 8612
j.duncan@ucl.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS 46471, IRAS 278210, WT 218380/Z/19/Z

Study information

Scientific title

Optimizing epilepsy surgery

Acronym

Study hypothesis

Computerised analysis of information from multiple brain scans will assist the neurosurgical treatment of epilepsy, at all steps along the pathway, particularly in designing the optimal surgical approach.

Ethics approval

Approved 10/09/2020, London - Queen Square Research Ethics Committee (HRA NRES Centre Bristol, 3rd floor, block B, Whitefriars, Lewins Mead, Bristol, BS1 2NT, UK; no telephone number provided; queensquare.rec@hra.nhs.uk), ref: 20/LO/0966

Study design

Non-randomised observational cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Epilepsy

Intervention

This programme of research has been developed with the benefit of input from individuals who have had or are considering epilepsy surgery for themselves or a loved one. This is the BrainBuddyUK group that meets every 2-3 months at NHNN.

A key feature of the output of the research is to develop clinical decision support tools to enable better decisions to be made, faster, but with experienced consultants remaining in control of the process.

The different aspects of this research will be appropriate at different points along the pathway of considering epilepsy surgery. The pathway for considering epilepsy surgery, with all the steps considered, may extend over 2 years. 150-200 patients per year consider epilepsy surgery at NHNN. Of these, approximately 40 per year may be offered resection without intracranial EEG, another 30 will require intracranial EEG, and the remainder will not proceed past the initial phase 1 investigations of MRI, scalp video-EEG telemetry, neuropsychology and neuropsychiatry assessments.

Potential participants will be those 70-100 per year who are eligible to proceed past phase 1 investigations, and who wish to do so. They will be identified by the clinical team and informed of the study and asked if they wish to know more. If the individual is interested, they will be notified to the research team who will make contact and explain the research study, sending written information about the study and asked to contact the research team if they wish to participate. If, after discussion and asking questions they wish to do so they will be asked to indicate their consent in writing on a consent form.

Individuals at the start of the evaluation of their epilepsy for possible epilepsy surgery will be asked a structured questionnaire of the symptoms. This will be supplemented by the account of a witness and of video recordings of seizures in the Hospital, which is standard clinical practice.

The planning of the strategy of brain areas to be implanted with electrodes and the precise planning of trajectories is made at a weekly MDT involving neurophysiologists, neurosurgeons, neurologists and imaging processing specialists. The suggestions for implantation from the symptom analysis will be compared with the MDT recommendations made without this consideration. The MDT will then have the option to modify the strategic plan.

The planning of precise electrode trajectories is made when the strategy has been agreed. Clinical standard care is to implant the agreed targets, to not pass within 3mm of an identified blood vessel, within 10mm of another electrode or cross sulci, and to cross the skull within 15 degrees of orthogonal, if possible, and to enter the brain at gyral crowns. In this project we will enhance this process by using as a starting point trajectories that have been used in previous successful implantations. As is clinical standard care, the treating consultant neurosurgeon checks the safety of each and every trajectory. No patient involvement in this process. After implantation, it is clinical standard care for X-ray CT and MRI scans to be carried out to determine the precise location of electrodes in the brain, and for the brain's electrical activity to then be recorded.

We will link the standard EEG display with electrode contacts in the brain, so that the anatomical source of electrical activity and epileptic discharges can be visualized in 3D, superimposed on the anatomical MRI. This supplements the current standard of the EEG reader inferring the anatomical location of electrode contacts. We will also compute and present in 3D derived EEG signals such as high frequency ripples and Gamma power.

Clinical standard care is that the area of seizure onset and early spread is manually drawn onto a diagram of the brain to suggest the area to be resected, with estimates of the chances of achieving seizure freedom. The plan is then reviewed with the neurosurgeon who will constrain the plan to avoid damaging known critical areas. The proposed resection is then discussed with the patient, with estimates of achieving seizure control and the risks of causing new morbidity.

Clinical standard practice is that consultant neurophysiologists mark electrode contacts that are involved in seizure onset, early propagation and in interictal epileptic activity and decide which areas of brain around these contacts should be removed to try to control epileptic seizures. In this project, we will display the EEG contacts that detect epileptic activity in a 3D map of the brain and will use a seed growing algorithm to create a model of the putative volume to be resected.

This volume will be dilated up to the gyral surface, and then constrained by the individual anatomy of eloquent cortex visualized with functional MRI and with imaging representation of critical white matter tracts. The brain surface of the intended volume of resection is then overlaid with imaging of arteries and veins, and with a model of the skull and scalp so that the neurosurgeon may plan the detail of the operative approach and resection. At all times the image guidance offered is subordinate to the clinical opinion of the treating consultants.

The same process for planning a resection is used for individuals who do not need intracranial EEG to identify the sites of seizure onset.

In this study, we will have the conventional method used, to result in a resection plan, and this will then be compared with a resection plan produced by the EpiNav tools. The treating consultant will select the plan that they consider is optimal in terms of likely benefit and risk avoidance.

The 3D plan of the resection volume and the operative approach is then uploaded to the clinically standard neuronavigation system used in the operating rooms, so that the margins of the planned resection and critical structures that must be spared are displayed in the operating surgeon’s eye piece.

These steps do not require patient participation, beyond the resection plan being viewable by the patient in the discussion with the neurosurgeon when considering whether to proceed. Prior to and 4 months after a resection, we will carry out functional language MRI and diffusion MRI scans, to determine the effects of the surgical resection on eloquent language cortex, and white matter tracts in the brain. These will be carried out at the same appointment as clinically required scans, so the individual is not inconvenienced.

In studies of this nature, developing novel clinical decision support tools, conventional power calculations are not appropriate. We intend to invite the circa 70 patients per year who proceed past phase one investigations, over three years.

The proportions of investigated patients proceeding to surgery will be noted; the occurrence of any complications of surgery will be assessed 3 months after surgery. The long-term outcomes of seizure freedom one year after resection will be determined 12 months after surgery. These rates will be compared with our recent rates for comparable patients, treated by the same multidisciplinary team.

By way of illustration, in an observational cohort study of anterior temporal lobe resections for mesial temporal lobe epilepsy using 3D imaging guidance to ensure inclusion of the piriform cortex in the resection and avoidance of language-related white matter tracts and of the optic radiation, 58 patients will give 90% power, p<0.05 one-tailed, to detect an increase in seizure freedom rate from 59% to 79%, compared to recent subjects operated upon by the same surgeons. In parallel we expect to reduce the incidence of word finding difficulties from 30% to 20% and of significant visual field defects from 15% to 0%.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Seizure freedom following neurosurgical treatment for refractory focal epilepsy using the Engel classification at pre-operation (baseline), 3 months post-operation, 1 year post-operation

Secondary outcome measures

1. Symptom analysis – measured by the extent of change in the planned implantation of SEEG electrodes from the original clinical data without the symptom analysis (single timepoint)
2. Optimal electrode planning: The time taken to plan a study is measured, as is the safety of the planned implantation (proximity to blood vessels) compared to previous recent data of implantations planned without the use of prior trajectories as a starting point (single timepoint, comparator is historical data)
3. Resection planning: comparison of the resection plan derived from the conventional method used, with the resection plan produced by the image-guided methods (comparison of volume to be resected, single timepoint once both resection plans are made)
4. Complications, causing neurological deficit, following neurosurgical treatment for refractory focal epilepsy, particularly deficits of language and visual fields after temporal lobe resection (formally measured by visual fields testing and language and memory assessments pre-operatively and 3 months post-operatively)

Overall trial start date

30/12/2019

Overall trial end date

30/09/2024

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Considering epilepsy surgery for drug-resistant focal epilepsy, at National Hospital for Neurology and Neurosurgery (NHNN)
2. Any gender, age 18-70 years
3. Has capacity to give informed consent
4. No contra-indication to neurosurgical intervention

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 300; UK Sample Size: 300

Participant exclusion criteria

1. Lack of capacity to give informed consent
2. Comorbidiites that would make neurosurgical intervention inappropriate (e.g., active neoplasia, cerebrovascular disease, dementia, coagulopathy)

Recruitment start date

01/10/2020

Recruitment end date

30/09/2023

Locations

Countries of recruitment

United Kingdom

Trial participating centre

National Hospital for Neurology and Neurosurgery
University College London Hospitals NHS Foundation Trust
London
WC1N 3BG
United Kingdom

Sponsor information

Organisation

University College London

Sponsor details

Joint Research Office
1st Floor
Maple House – Suite B
149 Tottenham Court Road
London
W1T 7DN
United Kingdom
+44 (0)20 3447 5696
uclh.RandD@nhs.net

Sponsor type

University/education

Website

http://www.ucl.ac.uk/

Funders

Funder type

Charity

Funder name

Epilepsy Research UK; Grant Codes: UK P1904

Alternative name(s)

ERUK

Funding Body Type

private sector organisation

Funding Body Subtype

Other non-profit organizations

Location

United Kingdom

Funder name

Wellcome Trust; Grant Codes: 218380/Z/19/Z

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

International organizations

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Intention to publish date

01/09/2025

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

02/10/2020: Internal review. 25/09/2020: Uploaded protocol (not peer reviewed) Version 3, 07 February 2020. 17/09/2020: Trial's existence confirmed by the NIHR.