Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001821280
Ethics application status
Approved
Date submitted
21/10/2018
Date registered
9/11/2018
Date last updated
23/04/2021
Date data sharing statement initially provided
9/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Brain Stimulation in Childhood Refractory Epilepsy
Scientific title
Transcranial Direct Current Stimulation for treatment of Children and
Adolescents with Refractory Epilepsy
Secondary ID [1] 289831 0
None
Universal Trial Number (UTN)
U1111-1186-0038
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 299759 0
Condition category
Condition code
Neurological 299694 299694 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Transcranial Direct Current Stimulation (tDCS)
tDCS will be applied using the NeuroConn DC stimulator. Surface stimulation will be applied using established protocols for cortical inhibition (usually 1-2mA for 15-60 minutes, 1-5 days per week for 1-2 weeks) at the discretion of neurologist.
Intervention code [1] 295510 0
Treatment: Devices
Comparator / control treatment
Changes in the type, frequency and duration of seizures for 2 weeks before and after tDCS will be compared based on seizure diary (maintained for 2 weeks prior to tDCS, during tDCS and 2 weeks after tDCS).
Control group
Uncontrolled

Outcomes
Primary outcome [1] 307846 0
Comparison of seizure frequency (based on patient diary) for 2 weeks prior and 2 weeks after treatment.
Timepoint [1] 307846 0
For 2 weeks before and after completion of treatment, then 3 and 6 months after treatment.
Secondary outcome [1] 353138 0
Comparison of seizure duration and severity (composite measure based on patient diary) for 2 weeks prior and 2 weeks after treatment.
Timepoint [1] 353138 0
For 2 weeks before and after completion of treatment, then 3 and 6 months after treatment..
Secondary outcome [2] 353139 0
Comparison of epileptiform activity (spike counts) on EEG 1 week before and after treatment.
Timepoint [2] 353139 0
1 week after treatment, then 3 and 6 months after treatment.
Secondary outcome [3] 353140 0
Quality of Life Questionnaire (QOLCE, Sabaz et al. 2000)
Timepoint [3] 353140 0
single time points 1-2 weeks before treatment, 1-2 weeks, 3 months and 6 months after treatment.
Secondary outcome [4] 353141 0
Changes in cortical excitability assessed with TMS (Resting or active motor threshold) 1-2 weeks before and after treatment.
Timepoint [4] 353141 0
single time point 1-2 weeks before and 1-2 weeks after treatment.
Secondary outcome [5] 353717 0
Changes in cortical excitability assessed with TMS (intra-cortical facilitation) 1-2 weeks before and after treatment.
Timepoint [5] 353717 0
single time point 1-2 weeks before and 1-2 weeks after treatment
Secondary outcome [6] 353718 0
Changes in cortical excitability assessed with TMS (intra-cortical inhibition) 1-2 weeks before and after treatment.
Timepoint [6] 353718 0
single time point 1-2 weeks before and 1-2 weeks after treatment

Eligibility
Key inclusion criteria
1) Children with refractory epilepsy (CRE), age 2 years or above
2) CRE who have trialled at least 4 AEDs (or 3 AEDs and a ketogenic diet)
3) CRE in whom epilepsy surgery is not a suitable option or where parents refuse surgery
Minimum age
2 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Children less than 2 years
2) Children in whom EEG cannot be undertaken
3) Children with significant psychiatric disorders
4) Children with implants not compatible with tDCS or TMS (e.g. cardiac pacemekers)

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)
None
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
Before and after treatment comparison. Open label trial.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
We plan to recruit 10 children with focal epilepsy and 10 with generalized epilepsy to investigate consistent effects of tDCS in children with refractory epilepsy. The patient acts as his/her own control.
Appropriate statistical analyses (t-test, ANOVA) will be used to compare:
Seizure frequency and duration before and after tDCS (as calculated from seizure diaries kept for 2 weeks before tDCS, 2 weeks immediately after tDCS and at 3 months and 6 months after tDCS)
Epileptic burden on EEG will be assessed by doing spike counts (interictal epileptiform activity) before and after tDCS
QOLCE scores before and after tDCS
Cortical excitability parameters assessed by TMS before and after tDCS.
Subgroup analysis will be performed to evaluate if beneficial effects of tDCS are related to type of epilepsy or other patient chanracteristics.
Corrections will be made for multiple comparisons.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
14/04/2015
Date of last participant enrolment
Anticipated
14/04/2022
Actual
Date of last data collection
Anticipated
14/10/2022
Actual
Sample size
Target
20
Accrual to date
5
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 12225 0
Princess Margaret Hospital - Subiaco
Recruitment hospital [2] 19181 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 24404 0
6008 - Subiaco
Recruitment postcode(s) [2] 33753 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 300989 0
Hospital
Name [1] 300989 0
Perth Children's Hospital
Country [1] 300989 0
Australia
Primary sponsor type
Individual
Name
Clinical Professor Lakshmi Nagarajan
Address
Perth Children’s Hospital
15 Hospital Avenue, Nedlands | Locked Bag 2010,
Nedlands WA 6909
Country
Australia
Secondary sponsor category [1] 300574 0
None
Name [1] 300574 0
Address [1] 300574 0
Country [1] 300574 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301748 0
Perth Children's Hospital Human Research Ethics Committee
Ethics committee address [1] 301748 0
Perth Children’s Hospital, 15 Hospital Avenue, Nedlands, Nedlands WA 6909
Ethics committee country [1] 301748 0
Australia
Date submitted for ethics approval [1] 301748 0
04/11/2013
Approval date [1] 301748 0
20/03/2014
Ethics approval number [1] 301748 0
HREC REF 2013114

Summary
Brief summary
Non-invasive brain stimulation with transcranial Direct Current Stimulation (tDCS) is being increasingly trialled for the treatment of neurological disorders such as stroke and epilepsy. Epilepsy is known to be associated with alteration in brain excitability. tDCS is a safe and painless neurophysiological method used to alter the excitability of the brain. Childhood epilepsy is refractory to medical management in 30% of children, and other options (e.g. surgery) are not appropriate in many. Newer techniques such as tDCS are being trialled and show promise as treatment options. There are, however, only a few studies involving small numbers that have been reported so far, and more trials with tDCS in epilepsy are needed. Our study plans to evaluate the use of tDCS in children with refractory epilepsy, to assess the types of seizures that will respond to tDCS, the stimulation protocols that produce optimal benefit, and to evaluate any other beneficial and adverse effects.

This study uses clinical assessments, EEG and transcranial magnetic stimulation (TMS) to monitor the effects of tDCS. Parents will be required to maintain a seizure diary to help evaluate the effects of tDCS.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67978 0
Prof Lakshmi Nagarajan
Address 67978 0
Perth Children’s Hospital, 15 Hospital Avenue,
Nedlands WA 6909
Country 67978 0
Australia
Phone 67978 0
+61 8 64564333
Fax 67978 0
+61 8 64562325
Email 67978 0
[email protected]
Contact person for public queries
Name 67979 0
Ms Linda Palumbo
Address 67979 0
Perth Children’s Hospital, 15 Hospital Avenue,
Nedlands WA 6909
Country 67979 0
Australia
Phone 67979 0
+61 8 64564333
Fax 67979 0
+61 8 64562325
Email 67979 0
[email protected]
Contact person for scientific queries
Name 67980 0
Prof Soumya Ghosh
Address 67980 0
Perth Children’s Hospital, 15 Hospital Avenue,
Nedlands WA 6909
Country 67980 0
Australia
Phone 67980 0
+61 8 64564333
Fax 67980 0
+61 8 64562325
Email 67980 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Funding not avaialable.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseTolerability and Effectiveness of Cathodal Transcranial Direct Current Stimulation in Children with Refractory Epilepsy: A Case Series.2023https://dx.doi.org/10.3390/brainsci13050760
N.B. These documents automatically identified may not have been verified by the study sponsor.