Feasibility Study: tDCS for Treatment of Refractory Status Epilepticus

NCT05934903 | Terminated

• 2 other identifiers: 2000035450No NIH funding
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Status epilepticus, or recurrent seizures without return to baseline, is a neurologic emergency. Refractory status epilepticus occurs when seizures are resistant to multiple first line anti-seizure medications. The ability to quickly stop seizures is paramount. Transcranial direct current simulation is a non-invasive, easily administered therapy that can potentially help reduce seizure burden. The goal of this feasibility study is to assess the ability of the study site to enroll patients admitted with refractory seizures or those with abnormal brain wave patterns to take part in a study looking to use transcranial direct current stimulation as an adjunctive treatment. The main questions it aims to answer are:

• What is the recruitment capability of the study site?
• How well can the study site adhere to study protocol?
• Are there any adverse effects of using the transcranial direct current stimulation device?
• How do patients' brain wave studies respond to the stimulation? Participants will be asked to consider joining the study. Once joined, researchers will randomly assign participants to compare transcranial stimulation versus sham stimulation to see if this will affect the participant's brain wave patterns.

Conditions

Status Epilepticus; Refractory Status Epilepticus

Keywords

Transcranial Direct Current Stimulation; Ictal-Interictal Continuum; Neurostimulation; Seizures; Epilepsy

Outcome Measures

Primary Outcomes (5)

• Recruitment capability of the study site- Incidence

  Recruitment capability of the study site will be assessed as the incidence of patients admitted with RSE/SRSE or IIC burden \> 50% within a 24 month period. Participants admitted undergoing cEEG monitoring will be screened for having RSE or IIC burden \>50% on a weekly basis.

  up to 24 months

• Recruitment capability of the study site- Prevalence

  Recruitment capability of the study site will be assessed as the prevalence of patients admitted with RSE/SRSE or IIC burden \> 50% within a 24 month period. Participants admitted undergoing cEEG monitoring will be screened for having RSE or IIC burden \>50% on a weekly basis. Prevalence will be calculated against weekly average patient census.

  up to 24 months

• Recruitment capability of the study site- Percent Eligible

  Recruitment capability of the study site will be assessed as the percent of eligible study participants compared to all patients admitted with RSE or IIC burden \>50% within a 24-month period.

  up to 24 months

• Recruitment capability of the study site- Percent Consent

  Recruitment capability of the study site will be assessed as the percent of eligible participants who consent for study

  up to 24 months

• Recruitment capability of the study site- Percent Withdraw

  Recruitment capability of the study site will be assessed as the percent of consented participants who withdraw consent.

  up to 24 months

Secondary Outcomes (12)

• Ability to implement protocol at study site

  up to 24 months

• Ability to implement protocol at study site- Protocol Deviations

  up to 24 months

• Ability to implement protocol at study site- Participants Lost to Follow Up

  up to 24 months

• Ability to implement protocol at study site- Device Failures

  up to 24 months

• Safety profile of tDCS by number of adverse events.

  up to 24 months

Study Arms (2)

Stimulation

EXPERIMENTAL

The tDCS device will stimulate with a 2mA current during sessions. Both arms receive application of the device for 3 sessions of 2x 30 minute active application with 30 minutes rest in between.

Device: Transcranial Direct Current Stimulation

Sham Stimulation

SHAM COMPARATOR

The tDCS device will stimulate with a 0mA current during sessions (sham). Both arms receive application of the device for 3 sessions of 2x 30 minute active application with 30 minutes rest in between.

Device: Transcranial Direct Current Stimulation

Interventions

Transcranial Direct Current Stimulation DEVICE

Cathodal direct current stimulation at 0 or 2mA will be applied to subjects

Sham Stimulation; Stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with refractory status epilepticus (RSE), or supra-refractory status epilepticus (SRSE), or electroencephalographic (EEG) characteristics \> 50% of the time on the ictal-interictal continuum (IIC) or epilepsia partialis continua for at least 12 hours.
• A patient with RSE is defined as having seizure(s) refractory to first line benzodiazepines and second-line antiseizure medications (ASMs; phenytoin, levetiracetam, valproate).
• A patient with SRSE is defined as:
• requiring at least 24 hours of a third-line intravenous anesthetic therapy (IVAT) such as propofol, midazolam, or ketamine, and
• failing at least one previous wean of an IVAT.
• A patient with epilepsia partialis continua (EPC) is defined as:
• having focal seizure(s) refractory to first line benzodiazepines and second-line ASMs and
• repeated episodes lasting more than one hour
• A patient on the IIC is defined as:
• having periodic discharges or rhythmic patterns at a rate at more than 1Hz and less than 3Hz and
• IIC patterns for more than 50% of the time (IIC burden = 50%) within any prior 12 hour interval.
• access to continuous EEG monitoring
• brain imaging (Computerized Tomography or Magnetic Resonance Imaging) within 1 year of presentation

You may not qualify if:

• Damaged skin on scalp as determined by the primary team that prevents reasonably accurate electroencephalography monitoring and which may interfere with tDCS stimulation.
• Cranial metal implants (\>1 mm thick epicranial titanium skull plates and metal dental fillings) or medical devices (i.e. cardiac pacemaker, deep brain stimulator, medication infusion pump, cochlear implant).
• Previous surgeries opening the skull leaving skull defects capable of allowing the insertion of a cylinder with a radius greater or equal to 5 mm.
• Presence of any disease, medical condition or physical condition that, in the opinion of the Investigators, may adversely impact the safety of the subject or the integrity of the data
• Those who are pregnant

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Related Publications (5)

• Trinka E, Rainer LJ, Granbichler CA, Zimmermann G, Leitinger M. Mortality, and life expectancy in Epilepsy and Status epilepticus-current trends and future aspects. Front Epidemiol. 2023 Feb 23;3:1081757. doi: 10.3389/fepid.2023.1081757. eCollection 2023.

  PMID: 38455899 BACKGROUND

• Fisher RS, McGinn RJ, Von Stein EL, Wu TQ, Qing KY, Fogarty A, Razavi B, Venkatasubramanian C. Transcranial direct current stimulation for focal status epilepticus or lateralized periodic discharges in four patients in a critical care setting. Epilepsia. 2023 Apr;64(4):875-887. doi: 10.1111/epi.17514. Epub 2023 Feb 7.

  PMID: 36661376 BACKGROUND

• Ng MC, El-Alawi H, Toutant D, Choi EH, Wright N, Khanam M, Paunovic B, Ko JH. A Pilot Study of High-Definition Transcranial Direct Current Stimulation in Refractory Status Epilepticus: The SURESTEP Trial. Neurotherapeutics. 2023 Jan;20(1):181-194. doi: 10.1007/s13311-022-01317-5. Epub 2022 Nov 2.

  PMID: 36323975 BACKGROUND

• Matsumoto H, Ugawa Y. Adverse events of tDCS and tACS: A review. Clin Neurophysiol Pract. 2016 Dec 21;2:19-25. doi: 10.1016/j.cnp.2016.12.003. eCollection 2017.

  PMID: 30214966 BACKGROUND

• Yang D, Wang Q, Xu C, Fang F, Fan J, Li L, Du Q, Zhang R, Wang Y, Lin Y, Huang Z, Wang H, Chen C, Xu Q, Wang Y, Zhang Y, Zhang Z, Zhao X, Zhao X, Li T, Liu C, Niu Y, Zhou Q, Zhou Q, Duan Y, Liu X, Yu T, Xue Q, Li J, Dai X, Han J, Ren C, Xu H, Li N, Zhang J, Xu N, Yang K, Wang Y. Transcranial direct current stimulation reduces seizure frequency in patients with refractory focal epilepsy: A randomized, double-blind, sham-controlled, and three-arm parallel multicenter study. Brain Stimul. 2020 Jan-Feb;13(1):109-116. doi: 10.1016/j.brs.2019.09.006. Epub 2019 Sep 24.

  PMID: 31606448 BACKGROUND

MeSH Terms

Conditions

Status Epilepticus; Seizures; Epilepsy

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Imran Quraishi, MD, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: The participant will not know the treatment arm, and the outcomes assessor reading electroencephalogram will not know treatment arm. The device does not have a sham mode so study personnel applying the device will be aware of the treatment arm.
• Purpose: DEVICE FEASIBILITY
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double blind block randomized into stimulation arm versus sham stimulation arm.

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: July 7, 2023
• Study Start: August 31, 2023
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: April 4, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)