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Trial registered on ANZCTR


Registration number
ACTRN12617001312336
Ethics application status
Approved
Date submitted
6/09/2017
Date registered
13/09/2017
Date last updated
23/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and Efficacy of a Deep Brain Stimulation System in Epilepsy: A Feasibility Study for Tracking Neural Excitability
Scientific title
Safety and Efficacy of a Deep Brain Stimulation System in Epilepsy: A Feasibility Study for Tracking Neural Excitability
Secondary ID [1] 292763 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 304558 0
Condition category
Condition code
Neurological 303881 303881 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study is testing a new device that uses electrical stimulation of the brain for the treatment of epilepsy, 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 hippopotamus and anterior nucleus of the thalamus,

Participants that agree to be part of the study will be asked to remain in the study for a total of 2 years from the date of the device implantation. This will involve eight clinic visits: at 10 days post implantation, 2, 4, 6, 7, 8, 12 and 24 months post implantation. Each visit will last between 1.5-2 hours and will involve neurological examination by the participants doctor, all device calibrations will be conducted by the doctor and research team. The study coordinator or study doctor may also call participants to ask about seizure diary entries and participants can call the study coordinator/doctor at any time with questions or concerns. . At the end of the study the participant and their doctor can decide if they would like to have the device removed or if they would like to keep it in place. Participants can end participation in the study and have the device removed and any time for any reason, or for no reason.

Surgical implantation will be conducted with participants under general anaesthesia. During the surgery, the doctor will make an incision in the scalp (less than 1 cm) and drill four holes (3 mm diameter) in the skull. The electrodes will be placed in the anterior nucleus of the thalamus and the hippocampus. The incision will be closed and the leads will be placed under the skin behind the ear, down each side of the neck and then to the Implantable pulse generators, placed under the skin, just below the collarbone.

In the recovery phase (2 months) of the study we will collect 30 second EEG snapshots recorded every 15 minutes.

Baseline phase:
Following the recovery period data will continue to be recorded to establish baseline data, There is no stimulation during this period. We require a minimum number of five seizures to occur during this phase. Expected duration is 2 months, no longer than 3 months. If it takes longer than that then participation may be discontinued.

Probing phase:
Following the baseline phase, the devices will be used to electrically stimulate (probe) the thalamus continuously at a low frequency (2 Hz). EEG snapshots will continue to be collected. This period lasts for a minimum of 2 months and no longer than 3 months. We require at least 5 seizures that are well separated in time to have occurred to proceed to the next phase.

Probe calibrated Deep Brain Stimulation (DBS) phase:
In this phase we explore 18 DBS 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 DBS parameter configuration will be tested for 1 minute with 4 minutes between each configuration test. The probing responses will be used to optimise the DBS parameters for each participant. This phase of the study continues for 2 months.

The final phase of the study continues until the end of the study (2 years). During this phase the DBS parameters may be altered from the probing optimised parameters according to patient needs.

Intervention code [1] 299013 0
Treatment: Devices
Intervention code [2] 299085 0
Treatment: Surgery
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 303242 0
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.
Timepoint [1] 303242 0
Recorded throughout the baseline (2-4 months post implant) and probe calibrated DBS phase( 6-8 months post implant)
Primary outcome [2] 303246 0
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.
Timepoint [2] 303246 0
Throughout probing phase (4-6 months post implant)
Primary outcome [3] 303247 0
Change in brain excitability following DBS treatment, assessed according to changes in probing response energy before and after stimulation therapy.
Timepoint [3] 303247 0
Throughout probing phase (4-6 months post implant) and probe calibrated DBS phase (6-8 months post implant).
Secondary outcome [1] 338344 0
Change in Seizure Rate

Assessed according to Seizure Diaries.
Timepoint [1] 338344 0
Recorded throughout the baseline phase (2-4 months post implant) and throughout the probe calibrated DBS phase (6-8 months post implant)

Eligibility
Key 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).

Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Presence of implanted electrical stimulation medical device anywhere in the body (e.g., cardiac pacemakers, spinal cord stimulator) or any metallic implants in the head (e.g., aneurysm clip, cochlear implant).

Previous diagnosis of psychogenic/non-epileptic seizures



Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 297450 0
Government body
Name [1] 297450 0
NHMRC
Address [1] 297450 0
GHD Building Level 1, 16 Marcus Clarke St, Canberra ACT 2601
Country [1] 297450 0
Australia
Funding source category [2] 297451 0
Commercial sector/Industry
Name [2] 297451 0
Medtronic
Address [2] 297451 0
678 Victoria St, Richmond VIC 3121
Country [2] 297451 0
United States of America
Primary sponsor type
Hospital
Name
St Vincent's Hospital
Address
41 Victoria Parade, Fitzroy VIC 3065
Country
Australia
Secondary sponsor category [1] 296446 0
University
Name [1] 296446 0
University of Melbourne
Address [1] 296446 0
Parkville VIC 3010
Country [1] 296446 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298496 0
Ethics committee address [1] 298496 0
Ethics committee country [1] 298496 0
Date submitted for ethics approval [1] 298496 0
Approval date [1] 298496 0
03/08/2017
Ethics approval number [1] 298496 0

Summary
Brief summary
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. We would like to show that this measure can be used to provide more effective deep brain stimulation therapies, to stop seizures.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77278 0
Prof Mark Cook
Address 77278 0
Department of Medicine, St Vincent's Hospital, University of Melbourne,
35 Victoria Parade, Fitzroy VIC 3065
Country 77278 0
Australia
Phone 77278 0
+61 3 9288 3068
Fax 77278 0
Email 77278 0
markcook@unimelb.edu.au
Contact person for public queries
Name 77279 0
Mrs Katrina Dell
Address 77279 0
Department of Medicine, St Vincent's Hospital
41 Victoria Parade, Fitzroy, VIC 3065
Country 77279 0
Australia
Phone 77279 0
+61 3 9231 3603
Fax 77279 0
Email 77279 0
katrina.dell@unimelb.edu.au
Contact person for scientific queries
Name 77280 0
Mrs Katrina Dell
Address 77280 0
Department of Medicine, St Vincent's Hospital
41 Victoria Parade, Fitzroy, VIC 3065
Country 77280 0
Australia
Phone 77280 0
+61 3 9231 3603
Fax 77280 0
Email 77280 0
katrina.dell@unimelb.edu.au

No data has been provided for results reporting
Summary results
Not applicable