Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000735459
Ethics application status
Approved
Date submitted
16/06/2025
Date registered
11/07/2025
Date last updated
11/07/2025
Date data sharing statement initially provided
11/07/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
A trial of non-invasive brain stimulation to treat patients with severe epilepsy
Scientific title
A pilot trial of transcranial magnetic stimulation to treat epilepsy of Lennox-Gastaut phenotype in individuals aged 15-50 years on an established anti-seizure medication regimen.
Secondary ID [1] 314655 0
nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lennox-Gastaut Syndrome 337830 0
Condition category
Condition code
Neurological 334164 334164 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Transcranial magnetic stimulation will be adminstered via an air-cooled figure of eight coil connected to a commerical stimulator (Magstim Rapid Plus). This will be performed in a dedicated laboratory in the Melbourne Brain Centre, on the Austin hospital Heidelberg campus. The target of stimulation will be defined using coordinates derived from previous EEG-fMRI studies looking at peak group level activation from inter-ictal epileptiform discharges in 25 patients. Two targets will be defined for each patient (one per brain side) located in Brodmann area 9 and 46 in the region of dorsolateral prefrontal cortex. Neuronavigational software on the Brainsight (Symbiotic devices, Melbourne) will be used to display the target on patient's own MRI.

Continuous theta-burst TMS will be applied to these targets., The stimulation protocol is a session of 12 spaced trains of theta-burst TMS (600 pulses per train with each train lasting 40 seconds). There will be a 5 minute rest interval between trains. Stimulation will alternate between sides (6 trains over each side). The session will last approximately an hour. Treatment will be one session a day for 5 consecutive days.

Prior to the treatment phase, there will be a 4 week baseline period. During this period, participants will be asked to keep a paper seizure diary as well as undertaking a 24 hour EEG and an MRI scan. Participants will also be asked to keep their usual treatment regimen stable. The seizure diary forms will be provided to all participants to fill in.

Dosage of TMS will be based off resting motor threshold (RMT), measured from EMG over the abductor pollicis brevis defined as lowest threshold to get 5 or more evoked potenials out of 10 attempts at APB. On the first day, the intensity of TMS will be set as 80% of RMT and will be increased by 5% each session as tolerated (i.e 85% of RMT on day 2, 90% of RMT on day 3, 95% of RMT at day 4 and 100% of RMT at day 5). Tolerability will be defined as absence of muscule discomfort, headache or localised pain at scalp stimulation site. If RMT is unable to be measured, then intensity will be set at 80% of maximum intensity output of the TMS machine and a similar uptitration of dosing will occur.

Strategies to improve adherence will include demonstration of the devices before sessions, presence of carers/parents during sessions, distractions including toy or ipads. If a train is interrupted due to participant's moving away, the train will be repeated. Study notes will be kept during the studies including a checklist of completed sessions to measure adherence.
Intervention code [1] 331284 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 341815 0
Safety
Timepoint [1] 341815 0
Safety will be monitored during the baseline 4 week period via self-reporting by carers/parents with a scheduled visit occuring just prior to intervention commencement. There will be two visits in the post-intervention 8 weeks period at 4 weeks and 8 weeks with also carers reporting via direct contact to subinvestigators any concerns outside of these visits.
Primary outcome [2] 341934 0
Feasibility
Timepoint [2] 341934 0
Upon completion of study
Secondary outcome [1] 448772 0
Seizures/Preliminary efficacy - diary recorded seizures
Timepoint [1] 448772 0
continuously measured during baseline 4 week period. Also measured over the 1 week intervention period then continuously during the 8 week period post completion of intervention.
Secondary outcome [2] 449058 0
Inter-ictal epileptiform discharge counts
Timepoint [2] 449058 0
At one time point during 4 week baseline period prior to intervention commencement and then another timepoint 4 weeks after completion of intervention (during the 8 week post completion of intervention phase.
Secondary outcome [3] 449059 0
Cognitive function
Timepoint [3] 449059 0
During one timepoint during baseline 4 week period prior to intervention commencement as well as a timepoint one day post treatment phase and another time point 8 weeks after treatment.
Secondary outcome [4] 449060 0
Behavioural function
Timepoint [4] 449060 0
At one timepoint during baseline 4 week period prior to intervention commencement as well as one day post treatment phase and another timepoint 8 weeks after treatment.
Secondary outcome [5] 449061 0
Quality of Life
Timepoint [5] 449061 0
At one timepoint during baseline 4 week period prior to intervention commencement as well as one day post treatment phase and another timepoint 8 weeks after treatment.
Secondary outcome [6] 449404 0
EEG measured seizure frequency - preliminary efficacy
Timepoint [6] 449404 0
24 hour EEG completed during at one time point during the 4 week baseline period prior to intervention commencement and then another EEG at a timepoint 4 weeks post completion of intervention.
Secondary outcome [7] 449405 0
Health Impact of Epilepsy
Timepoint [7] 449405 0
At one timepoint during baseline 4 week period prior to intervention commencement as well as one day post treatment phase and another timepoint 8 weeks after treatment.
Secondary outcome [8] 449406 0
Level of disability
Timepoint [8] 449406 0
At one timepoint during baseline 4 week period prior to intervention commencement as well as one day post treatment phase and another timepoint 8 weeks after treatment.

Eligibility
Key inclusion criteria
Meets diagnostic criteria of Lennox-Gastaut Syndrome, aged 15-50 years old, taking more than or equal to 2 anti-seizure medications, seizure frequency of more than or equal to 4 seizures per month, amenable to frequent hospital visits, able to maintain an accurate seizure diary (patient or carer)
Minimum age
15 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Existing metallic items implanted in or near the head, such as deep brain stimulation devices; unable to tolerate stable anti-seizure drug regimen during the trial period, unable to pass the internation federation of clinical neurophysiology's 13-item Transcranial magnetic stimulation safety screening questionaire

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
Statistical methods / analysis
Primary outcomes will not rely on quantative statistical tests. The trial will be considered to show feasibility if the patient retention rate is at least 80%, and there are no SAEs deemed causally related to TMS. Seizure reduction is a secondary outcome and preliminary efficacy will be shown to be clinically meaningful if at least 30% of patients have a 50% reduction in seizures relative to the baseline period.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
14/07/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 28076 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 44280 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 319220 0
Hospital
Name [1] 319220 0
Austin Health
Country [1] 319220 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 321691 0
None
Name [1] 321691 0
Address [1] 321691 0
Country [1] 321691 0
Other collaborator category [1] 283549 0
University
Name [1] 283549 0
The Florey Institute of Neuroscience and Mental Health
Address [1] 283549 0
Country [1] 283549 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317798 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 317798 0
Ethics committee country [1] 317798 0
Australia
Date submitted for ethics approval [1] 317798 0
26/02/2020
Approval date [1] 317798 0
02/09/2021
Ethics approval number [1] 317798 0
HREC62149

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 142190 0
A/Prof John Archer
Address 142190 0
University of Melbourne Department of Medicine (Austin), 145 Studley Rd, Heidelberg VIC 3084
Country 142190 0
Australia
Phone 142190 0
+61 03 90357071
Fax 142190 0
Email 142190 0
[email protected]
Contact person for public queries
Name 142191 0
Michael Ginevra
Address 142191 0
University of Melbourne Department of Medicine (Austin), 145 Studley Rd, Heidelberg VIC 3084
Country 142191 0
Australia
Phone 142191 0
+61 0411782153
Fax 142191 0
Email 142191 0
[email protected]
Contact person for scientific queries
Name 142192 0
Michael Ginevra
Address 142192 0
University of Melbourne Department of Medicine (Austin), 145 Studley Rd, Heidelberg VIC 3084
Country 142192 0
Australia
Phone 142192 0
+61 0411782153
Fax 142192 0
Email 142192 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Study protocol    3_Study_Protocol_V2_CC_15Jul21.docx
Informed consent form    4_PICF-Interventional_Parent_and_Guardian_V2_Clean.docx
Ethical approval    20210902 LETTER HREC62149Austin2020 (Ethics - New Study).pdf


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.