Children's Adaptive Deep Brain Stimulation for Epilepsy Trial (CADET): Pilot (CADET Pilot)

The CADET Pilot will investigate the safety and feasibility of deep brain stimulation (DBS) to treat children with Lennox-Gastaut syndrome using a novel DBS device (Picostim DyNeuMo-1).

Following a 30-day preoperative/baseline assessment phase, all children will have a neurosurgical procedure to implant the device. Implantation will be followed by a 30-day phase of no stimulation (the device is off / inactive) and then a six-month phase of active stimulation (the device is on / active).

Study Overview

• Status: Recruiting
• Conditions: Epilepsy; Lennox-Gastaut Syndrome, Intractable
• Intervention / Treatment: Device: Deep brain stimulation

Detailed Description

The CADET pilot will be a single-arm, multi-site, interventional clinical trial. This design has been chosen since this is a feasibility and safety trial in a small number of patients and thus does not primarily aim to determine efficacy.

In this pilot clinical trial, four children with drug-resistant LGS will undergo bilateral CMN DBS.

Following the DBS insertion, all children will undergo one month of inactive ('off') DBS in order to allow the lesioning effect of electrode implantation to dissipate. Thereafter, children will receive active ('on') DBS therapy with standard stimulation parameters for six-months. Following the 'on' phase of the trial, the child will then transition into continuing clinical care and will have their stimulation parameters altered according to clinical evaluation.

• Study Type: Interventional
• Enrollment (Estimated): 4
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rory J Piper, MRCS; Phone Number: 20 7405 9200; Email: rory.piper.20@ucl.ac.uk
• Study Contact Backup: Name: Martin M Tisdall, FRCS; Phone Number: 20 7405 9200; Email: m.tisdall@ucl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • Not yet recruiting
    • King's College Hospital NHS Foundation Trust
    • Contact: Antonio Valentin, PhD
  • London, United Kingdom
    • Recruiting
    • Great Ormond Street Hospital NHS Foundation Trust
    • Contact: Rory Piper, MRCS
    • Contact: Martin Tisdall, FRCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 14 years (Child)
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA:

Children enrolled in this study must:

1. Be 5-14 years of age at consent.

2. Have a diagnosis of Lennox-Gastaut Syndrome, as determined by:

   • Slow (<3.0Hz) spike-and-wave pattern and/or fast wave pattern (tonic seizures) on EEG for at least six-months months prior to the enrolment into the baseline period
   • History of drop seizures (tonic, atonic, or tonic-clonic) for at least six-months prior to the enrolment into the baseline period
3. Experience at least 10 seizures per month.
4. Have tried and not responded to two or more antiseizure medications prior to enrolment.
5. Be taking one or more anti-seizure medication(s) at a stable dose for at least the four weeks prior and have a parent/guardian(s) who is willing for their child's maintenance anti-seizure drugs to be unaltered for the trial duration.
6. If on a ketogenic diet, have been established on a stable ketogenic diet for at least 12 weeks prior to screening and the parent/guardian(s) to be willing for child to stay on a stable ketogenic for the duration of the trial.

7. Have a parent/guardian(s) who is willing and able to comply with all the requirements of the study, including the completion of the seizure diary and periodic device charging.

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EXCLUSION CRITERIA:

Children enrolled in this study must not:

1. Have had prior deep brain stimulation insertion.
2. Have an active ('on') vagus nerve stimulator (or active within the six months prior to the baseline period).
3. Have abnormal thalamic anatomy detected on imaging that would render DBS either unsafe or unfeasible.
4. Have a bleeding disorder.
5. Have medical conditions/factors that would increase their anaesthetic risk to an unacceptable level.
6. Have a nickel allergy
7. Be pregnant
8. Participate in contact sports

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: Deep brain stimulation; Deep Brain stimulation using a novel device: Bioinduction "Picostim" Deep Brain Stimulation system.	Device: Deep brain stimulation; Deep brain stimulation of the centromedian nucleus (bilateral)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse evens	Measured according to pre-determined device-related AEs and SAEs, as well as generic AEs and SAEs.	Following 6-months of active stimulation
Willingness of the participants/parents/guardians for the participant to be recruited into the study and to undergo the intervention	Consent at baseline	Following 6-months of active stimulation
Participant completion of the study	Completion of all study activities at study exit	Following 6-months of active stimulation
Ability of the participant/parent(s)/guardian(s) to re-charge and maintain the device	Device recharging is measured using the Picostim event logs	Following 6-months of active stimulation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change in parent-reported seizure frequency	Measured using parent-reported diaries	Following 6-months of active stimulation (compared to baseline)
Relative change in electrographic-recorded seizure frequency	Measured using serial electroencephalography (EEG)	Following 6-months of active stimulation (compared to baseline)
Relative change in seizure severity	Measured using the Hague Seizure Severity Scoring questionnaire. Minimum score = 13; maximum score = 52; with higher seizure severity with ascending values.	Following 6-months of active stimulation (compared to baseline)
Relative change in quality of life	Measured on the Pediatric Quality of Life Inventory (PedsQL) questionnaire. The minimum score is 0 and the maximum score is 100, with improving quality of life with ascending values.	Following 6-months of active stimulation (compared to baseline)
Relative change in quality of life	Measured on the Impact of Pediatric Epilepsy Scale (IPES) questionnaires. The minimum score is 0 and the maximum score is 100, with improving quality of life with ascending values.	Following 6-months of active stimulation (compared to baseline)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiological correlates of neurophysiological and clinical response to CMN DBS	Analysis of pre-trial MRI brain scan in conjunction with relative change in seizure counts measured using parent-reported diaries	Following 6-months of active stimulation
Correlates of the scalp EEG with the intracranial recordings (local field potentials) from the DBS device.	Analysis of local-field potentials measured from the DBS device in conjunction with data from the encephalography (EEG) data	Following 6-months of active stimulation

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: King's College London; King's College Hospital NHS Trust; University of Oxford; Great Ormond Street Hospital for Children NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2023
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: June 20, 2022
• First Submitted That Met QC Criteria: June 24, 2022
• First Posted (Actual): June 29, 2022

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 5, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Epilepsy; Neuromodulation; Deep brain stimulation; Lennox-Gastaut Syndrome; Neurostimulation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Genetic Diseases, Inborn; Epilepsy; Lennox Gastaut Syndrome
• Other Study ID Numbers: 141267

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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