Clinical trial NCT05934903: Feasibility Study: tDCS for Treatment of Refractory Status Epilepticus
Official title: Feasibility Study: tDCS for Treatment of Refractory Status Epilepticus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Status Epilepticus
Refractory Status Epilepticus
Keywords: Transcranial Direct Current Stimulation
Ictal-Interictal Continuum
Neurostimulation
Seizures
Epilepsy
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2023-07-07
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind block randomized into stimulation arm versus sham stimulation arm.
Primary purpose: DEVICE_FEASIBILITY

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.

Detailed description: This is study is designed to determine the feasibility of implementing a double-blinded tDCS in inpatients with status epilepticus and other abnormal EEG (electroencephalography) patterns. The study includes assessments of recruitment capability, the ability to implement the study procedures, the safety profile, and preliminary evaluation of participant response to transcranial direct current stimulation (tDCS) therapy, to see which clinical outcome measures are most practical.

Patients who are admitted to Yale New Haven Hospital with refractory status epilepticus or EEG patterns falling on the ictal-interictal continuum (IIC, rhythmic or periodic patterns with rates more than 1Hz and less than or equal to 2.5Hz) will be recruited, starting from August 1st 2023 until July 31st 2025, or until 60 total participants, whichever is sooner. Those who are eligible will be randomized into two groups: stimulation or sham, all while receiving standard of care according to their primary teams.

Each subject will receive up to 3 sessions of tDCS over a 72 hour period with at least 24 hours between each session. Each session will consist of 30 minutes of stimulation (or sham), a 30 minute break and a second 30 minute of stimulation (or sham). Stimulation will be applied using the ActivaDose II device (Caputron). Saline soaked sponges will be prepared, with the cathode being placed on the area corresponding to the seizure focus or point of maximal epileptic potential as defined on the international 10-20 EEG system. The anode will be placed on the contralateral shoulder. During each session, a maximum of total injected current across the electrodes of 2mA will be used, as conventional tDCS with 2mA is well-tolerated in adults and children. Sham stimulation includes application of the electrodes and timing the device to deliver 0mA of injected current.

The patients will not be aware of their randomization arm. The research staff analyzing the EEG data will not be aware of the patient's treatment arm.

The study schedule will include:

1. Screening and Consent visit
2. Stimulation Sessions - 3 one-hour stimulation sessions, distributed over 72 consecutive hours, and no less than 24 hours apart.
3. Follow up visit at 30 days after intervention.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Recruitment capability of the study site- Incidence
timeFrame: up to 24 months
measure: Recruitment capability of the study site- Prevalence
timeFrame: up to 24 months
measure: Recruitment capability of the study site- Percent Eligible
timeFrame: up to 24 months
measure: Recruitment capability of the study site- Percent Consent
timeFrame: up to 24 months
measure: Recruitment capability of the study site- Percent Withdraw
timeFrame: up to 24 months
Secondary outcomes:
measure: Ability to implement protocol at study site
timeFrame: up to 24 months
measure: Ability to implement protocol at study site- Protocol Deviations
timeFrame: up to 24 months
measure: Ability to implement protocol at study site- Participants Lost to Follow Up
timeFrame: up to 24 months
measure: Ability to implement protocol at study site- Device Failures
timeFrame: up to 24 months
measure: Safety profile of tDCS by number of adverse events.
timeFrame: up to 24 months
measure: Safety profile of tDCS by number of serious adverse events.
timeFrame: up to 24 months
measure: Preliminary evaluation of effect of tDCS- Change in Time to resolution of status epilepticus
timeFrame: Baseline, 12 hours, 24 hours, 7 days, and 30 days
measure: Preliminary evaluation of effect of tDCS- Change in Seizure Burden
timeFrame: Baseline, 12 hours, 24 hours, 7 days, and 30 days
measure: Preliminary evaluation of effect of tDCS- Change in IIC burden
timeFrame: Baseline, 12 hours, 24 hours, 7 days, and 30 days
measure: Preliminary evaluation of effect of tDCS- Change in ASM burden
timeFrame: Baseline, 12 hours, 24 hours, 7 days, and 30 days
measure: Preliminary evaluation of effect of tDCS- Change in Acute Physiology and Chronic Health Evaluation (APACHE) II Score
timeFrame: Baseline and 7 days
measure: Preliminary evaluation of effect of tDCS- Change in modified Rankin Score
timeFrame: Baseline and 30 days
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
Study officials:
affiliation: Yale University
name: Imran Quraishi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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