Plain English Summary
Background and study aims
Epilepsy is a condition that affects the brain, which causes a person to experience seizures. It is estimated 1% of the population suffer from epilepsy and between 30-40% of these patients are unable to control their seizures despite trying two or more anti-epileptic drugs (drug refractory focal epilepsy). Surgical treatment can offer a potential cure for these patients. In order to find out if a patient is suitable to undergo surgery, they need to undergo a specialist evaluation to find the part of the brain that is causing the problem. In almost half of patients, performing non-invasive procedures such as brain scans are not enough to find the route of the problem, and so it is necessary to place electrodes (electrical conductors used to measure electrical activity) directly onto the exposed surface of the brain (Stereotactic EEG (SEEG) or depth electrodes). SEEGs carry a number of risks, including bleeding, infection and damage to important brain structures if they are misplaced. The accurate placing of depth electrodes is therefore very important. The iSYS1 trajectory guidance system is a small robotic device that has been developed to improve the accuracy of depth electrode placement. The aim of this study is to investigate the use of the iSYS1 trajectory guidance system compared to the standard technique.
Who can participate?
Adults with drug refractory focal epilepsy who require a SEEG as part of routine clinical care
What does the study involve?
Participants who are having a SEEG as part of their normal care are randomly allocated to one of two groups. Those in the first group have the depth electrodes placed using the usual mechanical arm technique. This involves the use of a neuro-navigation system and the surgeon aligning a mechanical arm along a pre-planned trajectory (route). Once the trajectory has been lined up, a cut is made in the skin and a small hole is drilled through the skull. A metal bolt is then screwed into the skull through which the electrode is inserted along a premeasured length to reach the target in the brain. The electrode is then secured in place by the bolt. Those in the second group have the depth electrodes placed using the iSYS1 trajectory guidance system. This involves the use of a neuro-navigation system relaying the plan information to a small guidance system that the surgeon places a few centimetres from the surface of the scalp. The guidance system, through a series of small steps then aligns to the pre-planned trajectory with a high level of accuracy. Once the trajectory has been lined up, a cut is made in the skin and a small hole is drilled through the skull. A metal bolt is then screwed into the skull through which the electrode is inserted along a premeasured length to reach the target in the brain. The electrode is then secured in place by the bolt. The time taken for the electrodes to be placed in both groups is measured during the surgery. 48 hours after surgery, participants then undergo a brain scan to see how accurately the electrodes have been placed and check for any complications such as bleeding.
What are the possible benefits and risks of participating?
There are no direct benefits or risks involved with participating.
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?
January 2015 to January 2018
Who is funding the study?
Wellcome Trust (Grant number: WT106882) (UK)
Who is the main contact?
Professor John Duncan
j.duncan@ucl.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Prof John Duncan
ORCID ID
http://orcid.org/0000-0002-1373-0681
Contact details
UCL Institute of Neurology
Box 29
National Hospital for Neurology and Neurosurgery
Queen Square
London
WC1N 3BG
United Kingdom
+44 (0)20 3448 8612
j.duncan@ucl.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
16/0590
Study information
Scientific title
Single-blinded randomised case control parallel group single-site investigation of stereoencephalography electrode placement in patients with refractory focal epilepsy
Acronym
Study hypothesis
The use of the iSYS1 trajectory guidance system (Medizintechnik GmbH) in comparison to the conventional mechanical arm based technique (using the precision aiming device) will:
1. Reduce the operative time taken for target alignment and electrode insertion
2. Improve the accuracy of bolt entry point position at the skull compared to the pre-operative plan
3. Improve the accuracy of electrode target point position compared to the pre-operative plan
4. Improve accuracy of angle of bolt insertion at the skull compared to the pre-operative plan
5. No increase in clinically significant and non-clinically significant radiological post-operative haemorrhage rate
6. No increase in infection rate
7. No increase in new post-operative neurological deficits
Ethics approval
Not provided at time of registration
Study design
Single-blinded randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Other
Patient information sheet
See additional files
Condition
Drug resistant focal epilepsy
Intervention
Patients who are scheduled for SEEG implantation as part of their routince medical care will be invited to take part in the study and are randomised by an independent statistician through the use of a computer generated system that contains a code assigning the patient to receive the current gold-standard method of implantation using the mechanical arm based technique (Precision-aiming device) or the robotic trajectory guidance system (iSYS1).
Group 1: Participants undergo surgery with the currently used mechanical arm based technique (using the precision aiming device) to place electrodes. The manual technique of SEEG placement involves the use of a neuronavigation system and the surgeon aligning a mechanical arm along a pre-planned trajectory. Once the trajectory has been aligned a skin incision is performed and a small hole is drilled through the skull. A metal bolt is then screwed into the skull through which the electrode is inserted along a premeasured length to reach the target in the brain. The electrode is then secured in place by the bolt.
Group 2: The iSYS1 trajectory guidance system (Medizintechnik GmbH) for aligning the trajectory of the electrodes to be placed. The iSYS1 trajectory guidance system technique of SEEG placement involves the use of a neuronavigation system relaying the plan information to a small guidance system that the surgeon places a few centimetres from the surface of the scalp and the guidance system, through a series of small steps will then align to the pre-planned trajectory with a high level of accuracy. Once the trajectory has been aligned a skin incision is then performed and a small hole is drilled through the skull. A metal bolt is then screwed into the skull through which the electrode is inserted along a premeasured length to reach the target in the brain. The electrode is then secured in place by the bolt.
Total duration of treatment is 3-4 hours for the SEEG surgery. Surgical implantation time will be measured during the surgery. Follow up will be in the form of a post-operative CT and MRI scan within 48 hours of surgery from which the accuracy data and complications (haemorrhage) will be determined. All other measures will be collected as part of ‘routine care’ and will not fall within the trial duration.
Intervention type
Device
Phase
Drug names
Primary outcome measure
Surgical implantation time will be measured in minutes and seconds during surgery.
Secondary outcome measures
1. Accuracy of SEEG depth electrode placement, as assessed by skull entry point (mm), error of angle (degrees) of implantation of intracranial bolt and target point error (mm) of the actual electrode tip compared to the planned target point as defined by the preoperative plan and target region sampled, as lateral deviation measured by the research team from the CT/MRI scan following surgery
2. Incidence of clinically significant and non-clinically significant radiologically detected post-operative haemorrhages (%) is measured using post-operative imaging within 48 hours of implantation
3. Infection rate (%) is measured by the presence or absence of infection on clinical observation and corroborated by blood test markers of infection such as white cell count and C-reactive protein as appropriate by the clinical team at routine follow up or medical note review if the patient asks medical assessment prior to the routine follow up period.
4. New post-operative neurological deficits (%) are measured by the presence or absence of a new neurological deficit on clinical observation by clinical team at routine follow up
5. Operator (surgeon) based opinions for ease of use and perceived safety of the iSYS1 trajectory guidance system compared to conventional mechanical arm based insertion is measured by documenting comments at the end of each operation on the electronic clinical research form (eCRF).
6. Proportion of patients that are offered resective surgery and seizure freedom following resective surgery (if performed) is measured by medical note review at routine follow up
7. Number and nature of adverse events is measured by the medical note review by the clinical team at routine follow up
Overall trial start date
09/01/2015
Overall trial end date
31/05/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age 18-80 years
2. Drug refractory focal epilepsy
3. Deemed to require SEEG placement as part of routine clinical care following multidisciplinary team meeting decision
4. Informed consent from patient to undergo intracranial SEEG investigation as part of routine clinical care
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
32 (16 in each arm)
Total final enrolment
32
Participant exclusion criteria
1. Pregnancy
2. Uncorrectable coagulopathy
3. Lacking capacity to consent
Recruitment start date
01/02/2017
Recruitment end date
01/10/2018
Locations
Countries of recruitment
United Kingdom
Trial participating centre
National Hospital for Neurology and Neurosurgery
Queen Square
London
WC1N 3BG
United Kingdom
Funders
Funder type
Research organisation
Funder name
Wellcome Trust (Grant number: WT106882)
Alternative name(s)
Wellcome
Funding Body Type
private sector organisation
Funding Body Subtype
international
Location
United Kingdom
Results and Publications
Publication and dissemination plan
After completion of the study the results will be submitted for publication to an established peer reviewed journal and the data will also be presented at scientific forums/meetings. All proposed publications will be discussed with and reviewed by the Sponsor prior to publishing other than those presented at scientific forums/meetings.
IPD Sharing plan:
The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository, the UCL Data Repository. Requests for patient-level data and statistical code should be made to the corresponding author and will be considered by members of the original trial management group, including the chief investigator and members of the University Joint Research Office, who will release data on a case by case basis. Data will be shared following the principles for sharing patient-level data as described by Tudur Smith et al (BMC Medicine 2015; 13: 298). The data will not contain any direct identifiers, the researchers will minimise indirect identifiers, and remove free text data to minimize the risk of identification.
Intention to publish date
31/12/2019
Participant level data
Stored in repository
Basic results (scientific)
Publication list
Publication citations
Additional files
- ISRCTN17209025_PIS_14Nov2016_v1.docx Uploaded 15/11/2016