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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called transcranial direct current stimulation (tDCS) for refractory status epilepticus, a condition where seizures persist despite usual medications. Researchers aim to determine if tDCS can reduce seizure activity and if the study site can effectively manage the trial. Participants will be randomly assigned to receive either the real stimulation or a sham treatment for comparison. Individuals with ongoing seizures not helped by standard treatments might be suitable for this study. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatment options.

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 prior data suggests that the transcranial direct current stimulation device is safe for treating refractory status epilepticus?

Research has shown that transcranial direct current stimulation (tDCS) is generally safe for people with epilepsy. Studies have found that tDCS can help reduce seizures and is promising for those whose seizures do not respond to regular medications.

When testing tDCS, researchers observed a decrease in seizure frequency. For instance, some studies reported that seizure rates dropped by 28% to 49% in the months following treatment. Regarding side effects, tDCS is usually well-tolerated. Most people do not experience serious issues, though some might feel mild tingling or itching on the scalp where the device is placed.

Overall, evidence suggests that tDCS can be a safe option for managing seizures when other treatments are ineffective. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcranial direct current stimulation (tDCS) for refractory status epilepticus because it offers a non-invasive approach that differs from the typical use of medications like benzodiazepines and anesthetics. Unlike standard treatments that target chemical pathways, tDCS uses a mild electrical current applied to the scalp to modulate brain activity, potentially offering a new avenue for controlling seizures. This technique could provide a safer, less invasive option with fewer side effects, and it might be particularly beneficial for patients who do not respond well to traditional drug therapies.

What evidence suggests that transcranial direct current stimulation is effective for refractory status epilepticus?

Research has shown that transcranial direct current stimulation (tDCS) can reduce seizures, even when other treatments fail. In one study, tDCS lowered the number of seizures by about 28% after one month and 49% after two months. Another study found that tDCS significantly reduced seizure activity at 4 and 8 weeks. This method uses gentle electrical currents to affect brain function, calming the abnormal brain activity seen in epilepsy. In this trial, participants will be assigned to either a stimulation arm, where the tDCS device delivers a 2mA current, or a sham stimulation arm, where the device delivers a 0mA current. The treatment has been proven safe and effective for people with medication-resistant epilepsy. ^{2 3 4 6 7}

Who Is on the Research Team?

Imran Quraishi, MD, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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) 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]

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]

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]

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]

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 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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11067454/

High-definition transcranial direct current stimulation ...

We showed that high-definition transcranial direct current stimulation (hd-tDCS) can acutely reduce epileptic spike rates during and after stimulation in ...

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0920121124001712

A meta-analysis of RCTs and non-RCTs

tDCS significantly reduced seizures at 4 weeks and 8 weeks , with improvements in epileptiform discharges. •. Mechanisms, influencing factors, and advances like ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05934903

Feasibility Study: tDCS for Treatment of Refractory Status ...

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 ...

4.

frontiersin.org

frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1462364/full

Transcranial direct current stimulation in the management ...

Our results indicated that tDCS reduced seizure frequency by ~28 and 49% within 1- and 2-month follow-ups post-treatment, respectively. Further ...

5.

link.springer.com

link.springer.com/article/10.1007/s10072-024-07866-1

Efficacy and safety of transcranial direct current stimulation ...

This study aims to provide a comprehensive investigation of the efficacy and safety of tDCS in patients with drug-resistant epilepsy.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11772517/

Efficacy and safety of transcranial direct current stimulation ...

We found that tDCS significantly reduces IEDs and SF in patients with drug-resistant epilepsy. Active tDCS was more effective than sham tDCS in ...

7.

bmcneurol.biomedcentral.com

bmcneurol.biomedcentral.com/articles/10.1186/s12883-024-03907-6

TRANscranial direct current stimulation for FOcal Refractory ...

We designed the first delayed start, double-blinded, sham-controlled study to evaluate the efficacy of tDCS as an adjunctive treatment for focal epilepsy.