tDCS for Refractory Status Epilepticus

Overseen By Duong Chu, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must be taking: Benzodiazepines, Antiseizure medications

Disqualifiers: Cranial metal implants, Skull defects, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 33

Duration: 72 hours

4 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, since it involves patients with seizures resistant to multiple medications, it's likely that you will continue your current treatment while participating.

What data supports the effectiveness of the treatment Transcranial Direct Current Stimulation (tDCS) for Refractory Status Epilepticus?

Research shows that tDCS, a non-invasive brain stimulation technique, can reduce seizures and improve outcomes in epilepsy. Studies in both humans and animals have demonstrated its potential to decrease seizure activity and related symptoms. ^{1 2 3 4 5}

Is transcranial direct current stimulation (tDCS) safe for humans?

Transcranial direct current stimulation (tDCS) is generally considered safe for humans, with over 33,200 sessions showing no serious adverse effects. Common mild side effects include itching, tingling, and headaches, which are usually temporary. ^{4 6 7 8 9}

How does the treatment tDCS differ from other treatments for refractory status epilepticus?

tDCS (transcranial direct current stimulation) is unique because it is a non-invasive brain stimulation technique that uses a small electrical current applied to the scalp to reduce seizure activity. Unlike traditional treatments that involve intravenous drugs with severe side effects, tDCS targets specific brain areas with minimal risk, making it a safer alternative for managing refractory status epilepticus. ^{1 2 3 5 10}

Research Team

Imran Quraishi, MD, PhD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for patients with severe, ongoing seizures not controlled by standard medications. They must have access to continuous EEG monitoring and brain imaging within the last year. It's not suitable for pregnant individuals, those with scalp issues affecting EEG readings, or people with certain metal implants or devices in their body.

Inclusion Criteria

I have had severe seizures requiring strong IV medication for over 24 hours and failed at least one attempt to reduce the medication.

My seizures did not stop with first and second-line seizure medications.

You have had a brain scan (CT or MRI) within the past year.

Exclusion Criteria

I've had surgery on my skull that left a space big enough for a small cylinder.

You have metal implants in your head or medical devices like a pacemaker or cochlear implant.

You have skin damage on your scalp that could make it difficult to monitor brain activity accurately or interfere with tDCS treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 24 months

Screening and Consent visit

Treatment

Participants receive up to 3 sessions of tDCS or sham stimulation over a 72-hour period

72 hours

3 sessions, each consisting of 2x 30-minute applications with 30-minute rest in between

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Follow-up visit at 30 days after intervention

Treatment Details

Interventions

• Transcranial Direct Current Stimulation

Trial Overview Researchers are testing transcranial direct current stimulation (tDCS) as an additional treatment for refractory status epilepticus. The study will randomly assign participants to receive either tDCS or a sham stimulation to see if it influences their brain wave patterns.

Participant Groups

Group I: Stimulation Experimental Treatment 1 Intervention

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.

Group II: Sham Stimulation Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Findings from Research

Transcranial direct current stimulation (tDCS) applied at 2 mA over the seizure focus in four patients with focal status epilepticus led to significant reductions in interictal spikes and electrographic seizures, demonstrating its potential efficacy in critical care settings.

The treatment was well-tolerated with only minor side effects, and it allowed for reductions in antiseizure medications, suggesting a promising role for tDCS in managing refractory seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for focal status epilepticus or lateralized periodic discharges in four patients in a critical care setting. Fisher, RS., McGinn, RJ., Von Stein, EL., et al.[2023]

Cathodal transcranial direct current stimulation (tDCS) significantly reduced convulsions by 21% and protected against hippocampal cell loss in immature rats following status epilepticus, suggesting its potential as a neuroprotective treatment.

The tDCS treatment not only decreased seizure activity but also improved cognitive performance in spatial learning tasks, indicating its efficacy in addressing both seizure control and cognitive impairment after brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation decreases convulsions and spatial memory deficits following pilocarpine-induced status epilepticus in immature rats. Kamida, T., Kong, S., Eshima, N., et al.[2022]

Transcranial direct current stimulation (tDCS) significantly reduced interictal spike counts in rats with chronic seizures immediately after treatment, suggesting its potential efficacy in modulating epileptic activity.

The study found that enhanced delta oscillations during tDCS may underlie its inhibitory effects on seizure excitability, while changes in BDNF protein expression indicate a complex interaction between tDCS and neural mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta oscillation underlies the interictal spike changes after repeated transcranial direct current stimulation in a rat model of chronic seizures. Wu, YJ., Chien, ME., Chiang, CC., et al.[2022]

Transcranial direct current stimulation (tDCS) has shown preliminary safety and efficacy in reducing epileptic seizures in both animal studies and clinical trials involving 65 human participants, with 67% of studies reporting effective seizure reduction.

All patients tolerated tDCS well, indicating a favorable safety profile, but further research is needed to establish optimal stimulation protocols and assess long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation in Epilepsy. San-Juan, D., Morales-Quezada, L., Orozco Garduño, AJ., et al.[2018]

In a study of 12 patients with drug-resistant mesial temporal lobe epilepsy with hippocampal sclerosis, cathodal transcranial direct current stimulation (tDCS) significantly reduced seizure frequency from an average of 10.58 to 1.67 seizures per month (p=0.003).

Eighty-three percent of patients experienced more than a 50% reduction in seizures after tDCS, with 50% becoming seizure-free for one month, indicating that tDCS could be a promising additional treatment option for patients awaiting or rejecting surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of transcranial direct current stimulation on seizure frequency of patients with mesial temporal lobe epilepsy with hippocampal sclerosis. Tekturk, P., Erdogan, ET., Kurt, A., et al.[2019]

Microdermabrasion significantly reduced skin resistance by about 32%, allowing for higher doses of transcranial direct current stimulation (tDCS) without increasing skin sensations or device limitations.

The study found that while microdermabrasion increased perceived sensations slightly when not combined with sonication, overall, it enabled safer and more effective delivery of tDCS by lowering the voltage needed to achieve the same current.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. Chhatbar, PY., Liu, S., Ramakrishnan, V., et al.[2023]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

Transcranial direct current stimulation (tDCS) is generally considered safe, with mild and transient adverse effects reported in clinical trials, but the frequency and relationship of these effects with clinical variables remain unclear due to selective reporting bias.

Out of 209 studies reviewed, 117 mentioned adverse effects, with common issues like itching and tingling reported more frequently in the active tDCS group, although these differences were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Brunoni, AR., Amadera, J., Berbel, B., et al.[2022]

A systematic review of 158 studies involving 4130 participants found that repeated sessions of transcranial direct current stimulation (tDCS) do not significantly increase the risk of adverse events compared to sham treatments.

The study indicated that adverse event rates were consistent across different diagnostic groups, suggesting that tDCS is generally safe for various populations, although the potential for rare adverse events cannot be completely excluded.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of repeated sessions of transcranial direct current stimulation: A systematic review. Nikolin, S., Huggins, C., Martin, D., et al.[2019]

High-definition transcranial direct current stimulation (hd-tDCS) was found to be a safe and non-invasive treatment for refractory status epilepticus (RSE), with no adverse events reported during 32 sessions across 10 patients.

The treatment led to a significant reduction in epileptiform activity, with median spike rates decreasing by 50% during hd-tDCS, and resulted in a 45.8% higher discharge rate from the ICU compared to historical controls, indicating potential for improved outcomes in RSE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of High-Definition Transcranial Direct Current Stimulation in Refractory Status Epilepticus: The SURESTEP Trial. Ng, MC., El-Alawi, H., Toutant, D., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for focal status epilepticus or lateralized periodic discharges in four patients in a critical care setting. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation decreases convulsions and spatial memory deficits following pilocarpine-induced status epilepticus in immature rats. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Delta oscillation underlies the interictal spike changes after repeated transcranial direct current stimulation in a rat model of chronic seizures. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation in Epilepsy. [2018]

5. Netherlands pubmed.ncbi.nlm.nih.gov

The effect of transcranial direct current stimulation on seizure frequency of patients with mesial temporal lobe epilepsy with hippocampal sclerosis. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

8. England pubmed.ncbi.nlm.nih.gov

A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Safety of repeated sessions of transcranial direct current stimulation: A systematic review. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

A Pilot Study of High-Definition Transcranial Direct Current Stimulation in Refractory Status Epilepticus: The SURESTEP Trial. [2023]