First-in-human Experience Using Novel Ultraflexible Low-impedance Electrode Arrays: an IDEAL Stage 1 Study

The goal of this first-in-human study is to evaluate a novel ultraflexible microelectrode in children undergoing neurosurgery to remove tissue that causes epilepsy (seizures) in focal cortical dysplasia (FCD) or long-term epilepsy-associated tumours (LEAT).

The main questions it aims to answer are:

1. The safety and feasibility of the novel microelectrode into current operative workflow
2. The unique electrophysiological tissue signatures in FCD or LEAT

Study Overview

• Status: Not yet recruiting
• Conditions: Epilepsy; Focal Cortical Dysplasia
• Intervention / Treatment: Device: Insertion of electrode during planned neurosurgery for epilepsy

Detailed Description

Epilepsy affects 100,000 people under 25. Many children with epilepsy also have a learning disability or developmental problems and 25-30% continue to have seizures despite best medical treatment.

Neuromodulation or brain stimulation is the delivery of electricity to the brain cells. It may alter the brain activity and overall brain connectivity and currently is rarely used as a treatment for epilepsy. However, it has the potential to reduce the number of seizures and improve other problems that children with epilepsy may have such as concentration, memory and learning. 'Precision neuromodulation', which involves individually tailored treatments requires us to identify where in the brain to stimulate and what the best settings are in each individual. A limitation of current neuromodulation treatment is limited understanding of the abnormal signatures of electrical activity in abnormal tissue.

The investigators have developed a novel electrode that can record signals from the brain at higher resolution than current electrodes. The 2 micrometer, ultraflexible, low-impedance electrode arrays are smaller, less damaging, and provide multiple contacts at multiple depths. The investigators propose a first-in-human study to investigate the feasibility and safety of using these electrodes in patients undergoing surgery for epilepsy - either focal cortical dysplasia (FCD) or long-term associated epilepsy tumours (LEAT).

The investigators will insert the electrode into brain tissue that is going to be removed as part of the planned surgery. The extent of tissue damage caused by insertion will be examined, and whether the electrode is able to capture signals at difference scales from the brain will be assessed; this includes signals from an area of tissue (termed local field potential) and signals from single nerve cells (termed single unit recordings). If safe, it will lay the foundation to use these electrodes in future precision neuromodulation platforms that can be applied to epilepsy and other neurological diseases.

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Martin Tisdall, MD FRCS; Phone Number: 07726780817; Email: martin.tisdall@gosh.nhs.uk

Study Locations

• United Kingdom
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital
    • Contact: Martin Tisdall, MD FRCS; Phone Number: 07726780817; Email: martin.tisdall@gosh.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Radiologically visible epileptogenic lesion (focal cortical dysplasia or long-term epilepsy associated tumour) undergoing planned resective surgery

Exclusion Criteria:

1. Unable to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Insertion of electrode during planned neurosurgery for epilepsy; During the surgical procedure, following exposure of the brain via a craniotomy, the novel electrodes will be inserted into tissue planned for resection. This will be targeted using the existing neuronavigation software that is being used during the surgery and may be augmented by intraoperative ultrasound, also a common adjunct used in these surgeries. Following insertion of the electrode, the cables will be connected to a specialised (portable) amplifier inside the operating theatre and 15 minutes of data will be recoded. The electrodes will then be removed and the surgical resection will then proceed as planned. The content of the recordings will not be available in real-time and will not be used to inform or change the surgical resection plan in any way.

Device: Insertion of electrode during planned neurosurgery for epilepsy; A novel, 300 micrometer, ultraflexible, low-impedance electrode proposes to cause minimal parenchymal (brain tissue) damage, and provide multiple contacts at multiple depths to allow unit-level recordings for a period of 15 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of novel electrode into current operative workflow	Document total length of set up and recording with electrode (recorded in minutes)	At operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resected tissue assessed histologically for damage from novel electrode	Neuropathologists will perform haematoxylin and eosin histological (H&E), luxol fast blue, and neutral red to describe the insertion tract lesion and neocortical cytoarchitecture	4 weeks following operation
Analysis of recorded electrophysiological data from intraoperative recording by novel electrode	The data obtained from intraoperative recording will be analysed by computational neuroscientists	6 months
Safety of novel electrode insertion and recording	Intraoperative events occur (haemorrhage, seizure, stroke)	At operation

Collaborators and Investigators

• Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
• Investigators: Principal Investigator: Martin Tisdall, MD FRCS, Great Ormond Street Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: July 26, 2023
• First Submitted That Met QC Criteria: November 2, 2023
• First Posted (Estimated): November 3, 2023

Study Record Updates

• Last Update Posted (Estimated): November 3, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Epilepsy; Neurosurgery; Local field potential; FCD; LEAT; Microelectrode; Epileptic zone
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Congenital Abnormalities; Malformations of Cortical Development, Group I; Nervous System Malformations; Epilepsy; Malformations of Cortical Development; Focal Cortical Dysplasia
• Other Study ID Numbers: 21BI27

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No