A Deep Brain Stimulation System in Epilepsy: Tracking Neural Excitability

Safety and Efficacy of a Deep Brain Stimulation System in Epilepsy: A Feasibility Study for Tracking Neural Excitability

The main purpose of this research project is to evaluate the safety and effectiveness of a surgically implanted device called the Medtronic Activa PC+S System in patients with medically refractory epilepsy (people who have seizures that are not completely controlled by medical therapy). The system sends small electrical pulses into a part of the brain called the thalamus to help control seizures. It sends this signal in regularly, regardless of if a seizure is occurring. A different version of this device is already approved for the treatment of epilepsy in Australia. This study aims to use the brain's responses to single pulse electrical stimulation to measure the level of seizure susceptibility. The investigators would like to show that this measure can be used to provide more effective deep brain stimulation therapies, to stop seizures.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Nodular Heterotopia
• Intervention / Treatment: Device: Deep Brain Stimulation

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Victora
    • Melbourne, Victora, Australia, 3065
      • St Vincent's Hospital Melbourne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients with epilepsy with non-resectable pathologies, or clearly defined focal seizures without a defined structural pathology.

Patients will be required to have a seizure diary (of up to 3 months) recording at least five seizures per month that are well separated in time (at least 8 hours apart).

Exclusion Criteria:

Previous diagnosis of psychogenic/non-epileptic seizures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Recovery; Two months recovery (no stimulation) following bilateral implantation of Medtronic PC+S devices into the anterior nucleus of the thalamus and the hippocampus. Thirty second EEG snapshots will be recorded every 15 minutes
No Intervention: Baseline; No stimulation, 30 second EEG snapshots recorded every 15 minutes We require a minimum of 5 seizures to occur during this phase.
Experimental: Probing; Deep Brain Stimulation Electrically stimulate the thalamus continuously at a low frequency (2Hz). Thirty second EEG snapshots recorded every 15 minutes. We require a minimum of 5 seizures to occur during this phase.	Device: Deep Brain Stimulation; The device is called the Medtronic Activa PC+S system. Two devices will be implanted per participant. The electrodes will be surgically implanted bilaterally into the hippocampus and anterior nucleus of the thalamus.; Other Names: DBS
Experimental: Probe Calibrated Deep Brain Stimulation; Deep Brain Stimulation In this phase we explore 18 deep brain stimulation parameter configurations (three stimulus intensities; 3,4,5 Volts, six different frequencies; 125 130, 135, 140,145, 150 Hz) during two of the clinic visits. Each deep brain stimulation parameter configuration will be tested for 1 minute with 4 minutes between each configuration test. The probing responses will be used to optimise the deep brain stimulation parameters for each participant. This phase of the study continues for 2 months.	Device: Deep Brain Stimulation; The device is called the Medtronic Activa PC+S system. Two devices will be implanted per participant. The electrodes will be surgically implanted bilaterally into the hippocampus and anterior nucleus of the thalamus.; Other Names: DBS
Experimental: Open Deep Brain Stimulation; Deep Brain Stimulation During this phase the deep brain stimulation parameters may be altered from the probing optimised parameters according to patient needs.	Device: Deep Brain Stimulation; The device is called the Medtronic Activa PC+S system. Two devices will be implanted per participant. The electrodes will be surgically implanted bilaterally into the hippocampus and anterior nucleus of the thalamus.; Other Names: DBS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Seizure Rate	Comparing the number of seizures per patient, as recorded by Medtronic Activa PC+S system in the baseline vs. probe calibrated DBS phase.	Recorded throughout the baseline (2-4 months post implant) and probe calibrated DBS phase( 6-8 months post implant)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine if probing responses provide a seizure susceptibility measure.	Calculate probability of seizure in the near future given the features of the probing response shape during pre-ictal and inter-ictal periods on training dataset and then test predictive power on remaining data. Features defining the probing response shape will include peak amplitude and peak latency. Seizure occurrences will be determined by the Medtronic PC+S device.	Throughout probing phase (4-6 months post implant)
Change in brain excitability following DBS treatment, assessed according to changes in probing response energy before and after stimulation therapy.		Throughout probing phase (4-6 months post implant) and probe calibrated DBS phase (6-8 months post implant).

Collaborators and Investigators

• Sponsor: St Vincent's Hospital Melbourne
• Collaborators: University of Melbourne

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2018
• Primary Completion (Actual): July 1, 2020
• Study Completion (Actual): July 1, 2020

Study Registration Dates

• First Submitted: March 7, 2018
• First Submitted That Met QC Criteria: March 7, 2018
• First Posted (Actual): March 14, 2018

Study Record Updates

• Last Update Posted (Actual): October 27, 2020
• Last Update Submitted That Met QC Criteria: October 25, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: HREC/17/SVHM/146

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: Yes
• product manufactured in and exported from the U.S.: Yes