Transcranial Direct Current Stimulation in SUper REfractory STatus EPilepticus (SURESTEP): Pilot Study of a Novel Therapy in a Common Medical Emergency
Phase: NA
Conditions: Status Epilepticus
Sponsor: University of Manitoba

 
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PROTOCOL 
 
 
 
Title:   
SURESTEP: Transcranial Direct Current Stimulation in Super Refractory 
Status Epilepticus (SURESTEP) 
 
 
 
Principal Investigator:   
Marcus C. Ng, MD, FRCPC, CSCN; Neurology 
 
 
 
 
University of Manitoba 
 
 
 
Co-Investigators: 
 
Ji Hyun Ko, PhD; Human Anatomy and Cell Science 
 
 
 
 
University of Manitoba 
 
 
 
 
 
Bojan Paunovic, MD, FRCPC; Critical Care Medicine 
 
 
 
 
University of Manitoba 
 
 
 
NCT Number: 
NCT03819543 
 
 
 
Document Date: 
February 18, 2019 
 
 
 

 
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1. 
Specific Aims 
 
To investigate the efficacy of transcranial direct current stimulation (tDCS) in super refractory 
status epilepticus (SRSE), defined as: 
 
• Primary Outcome #1:  frequency of epileptiform activity on EEG 
 
• Primary Outcome #2:  severity of epileptiform activity on EEG (defined along the ictal-
interictal continuum) 
 
 
2. 
Study Design 
 
 
i.  ICU EEG Monitoring 
• The ICU team orders prolonged periods of live EEG monitoring (up to 
3 hours at a time) on SRSE patients to determine: 
o whether the patient continues to seize despite the presence of 
ongoing intravenous anaesthetic 
o whether it is safe to wean anaesthetic 
o whether the patient has stopped seizing off anaesthetic 
o if the patient has resumed seizing off anathesthic, then whether 
the patient is still seizing once anaesthetic is resumed. 
• During business hours, a live ICU EEG monitoring request is 
automatically honoured by the EEG technologist 
• After-hours (from 8 am to midnight for 7 days a week on all 365 days 
a year), the EEG request is first screened by the on-call neurologist 
o If the request is approved, then the request is forwarded to the 
EEG technologist.   
 
 
ii.  tDCS Set-Up & Application 
• tDCS will only be available when live EEG monitoring is available 
o tDCS can only be applied maximally once a day 
▪ Only one tDCS session per day 
▪ tDCS cannot be repeated in one day 
o tDCS can only be applied a maximum of 10 sessions over 10 
days 
▪ Although there is no harm, there is also no perceived 
benefit if tDCS has not shown benefit after at least 10 
sessions of stimulation 
• The “HD-targets” software (Soterix Medical, New York) will be used 
to determine the stimulation parameters to deliver a constant current of 
2.0 mA at the epileptogenic foci for 20 minutes 
o HD-targets uses a model human brain to estimate the focal 
delivery of direct current by adjusting current intensity of 8 
channels.  
o If the epileptogenic focus is diffuse or cannot be identified 
from EEG, then tDCS shall be applied to the right (non-
dominant) temporal pole 

 
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iii.  Real-Time Anaesthetic Management 
• Once the EEG technologist has finished their typical clinical set-up, 
live EEG data will start streaming to a non-blinded EEG reader (an 
epileptologist or a neurologist with special interest in EEG) at a remote 
location for interpretation.  
• Based on the EEG reader’s live report(s) to the ICU team, 
anaesthetic(s) may be changed 
o If the ICU elects to make no anaesthetic changes, then tDCS 
shall be applied right away 
o If the ICU elects to increase or decrease anaesthetic, then 
another 10 minutes shall elapse for the anaesthetic change to 
take effect prior to tDCS application 
• During real-time tDCS application, the EEG reader will determine 
efficacy by assessing whether there has been enough improvement in 
the frequency and severity of epileptiform activity (primary study 
outcomes #1 and #2) to warrant discontinuation (or continued 
discontinuation) of intravenous anaesthetic sedation to the end of the 
EEG recording (secondary study outcome) 
o Frequency of epileptiform activity (primary outcome #1)  is 
defined as the number of discharges per unit time (e.g. spikes 
per minute) 
o Severity of epileptiform activity (primary outcome #2) is 
defined by the morphology of the activity as outlined by the 
American Clinical Neurophysiology Society Standardized 
Critical Care EEG Terminology for the interictal-ictal 
continuum (e.g. spikes or sharp waves are more epileptiform 
than broad sharp waves or sharply contoured activity) 
o If tDCS unexpectedly worsens epileptiform activity, tDCS will 
be terminated immediately 
• After tDCS application is complete, the RA will remove all tDCS 
equipment from the patient and the bedside 
• The EEG reader will continue live-monitoring the study to ensure that 
any changes in the frequency and/or severity of epileptiform activity 
are enduring (i.e. persist through to the end of EEG recording) 
• Total EEG recording will be 3 hours as per the usual maximum ICU 
EEG recording duration protocol 
 
 
3. 
Statistical Analysis Plan 
• The primary study outcomes of epileptiform activity frequency before, during, and after 
tDCS will be analyzed on a per-stimulation session basis 
• The primary study outcomes of epileptiform activity frequency before, during, and after 
tDCS will also be analyzed on a per-patient session basis by averaging spike rates for all 
sessions in that patient 
• All data will be assessed for normality using the Shapiro-Wilk test 

 
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• Parametric tests will be used for normally distributed data and non-parametric tests will 
be used for non-normally distributed data in order to test before vs. during tDCS on per-
session and per-patient bases; and before vs. after tDCS on per-session and per-patient 
bases