TMS Therapy for Epilepsy

Overseen By Lalit Bansal, M.D.

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Children's Mercy Hospital Kansas City

Must be taking: Antiepileptic drugs

Disqualifiers: Metal implants, Cardiac pacemaker, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using a wearable device that emits magnetic pulses to help manage a specific type of epilepsy during sleep. The focus is on treating focal continuous-spike and wave during sleep (CSWS), a condition that disrupts brain activity during non-REM sleep. Known as Multisite Transcranial Magnetic Stimulation (mTMS), this treatment seeks children and young adults diagnosed with this type of epilepsy, particularly if their EEG (a brain activity test) shows a high spike rate during sleep. Participants should not have changed their epilepsy medication in the last two weeks or should not be on any medication. The goal is to determine if this device can reduce these disruptions and improve sleep quality for those affected. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance epilepsy management during sleep.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that there be no change in antiepileptic drugs (AED) in the last 2 weeks before joining. This suggests you may need to stay on your current AEDs without changes.

What prior data suggests that this wearable multisite transcranial magnetic stimulation device is safe for treating epilepsy?

Research has shown that multisite transcranial magnetic stimulation (mTMS) is a safe treatment. A review of studies found that repetitive transcranial magnetic stimulation (rTMS) is generally well-tolerated by people with epilepsy, with most experiencing no serious side effects. The review found no major negative effects from the treatment, indicating its general safety. mTMS, a type of rTMS, uses magnetic fields to stimulate the brain and is non-invasive, meaning it doesn't involve surgery or entering the body.

Prospective clinical trial participants should discuss any concerns with the study team. The team can provide more information about the treatment's safety based on the latest research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard epilepsy treatments, which often include medications like antiepileptics or invasive procedures such as surgery, Multisite Transcranial Magnetic Stimulation (mTMS) offers a non-invasive, targeted approach. Researchers are excited about mTMS because it uses magnetic fields to stimulate specific areas of the brain, potentially reducing seizure activity without the side effects associated with traditional drug therapies. This method could offer a novel treatment option for patients with focal CSWS, especially those who are not responding well to existing treatments.

What evidence suggests that this mTMS device is effective for epilepsy?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) may help treat epilepsy. One study found that a single session of rTMS reduced abnormal brain waves linked to epilepsy in two patients. Additionally, applying low-frequency rTMS to brain areas prone to seizures appears to be a safe and potentially effective non-invasive treatment for medication-resistant epilepsy. This trial will explore the effects of stimulating multiple brain areas with multisite transcranial magnetic stimulation (mTMS) to manage epilepsy symptoms, particularly in cases with continuous spikes and waves during sleep. ^{1 2 3 4 5}

Who Is on the Research Team?

Lalit Bansal, M.D.

Principal Investigator

Children's Mercy Hospital Kansas City

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 3 to 21 with a specific type of epilepsy called focal CSWS. They must have stable medication use for the last two weeks or not be on any epilepsy drugs, and their recent EEG should show a SWI of ≥ 85% during sleep.

Inclusion Criteria

Your previous or most recent EEG test showed a high SWI (sleep-wake instability) score of 85% or more.

I am between 3 and 21 years old.

You have been diagnosed with focal Continuous Spikes and Waves during Sleep (CSWS) as per medical guidelines.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time 10-minute TRPMS-ECA stimulation to assess immediate benefit and tolerability

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in Spike-Wave Index (SWI) and sustainability of effects post-stimulation

24 hours

Monitoring during sleep

Long-term follow-up

Participants are monitored for long-term effects and tolerability of TRPMS

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Multisite Transcranial Magnetic Stimulation (mTMS)

Trial Overview

The study tests a wearable device that uses transcranial magnetic stimulation (TMS) to target multiple areas of the brain either at once or in sequence, aiming to treat seizures associated with focal CSWS.

How Is the Trial Designed?

Group I: Treatment Group Experimental Treatment 1 Intervention

This study will be conducted over one year in 10 focal CSWS patients ranging in age from 3 to 21 years. The patients will be recruited from the large patient population that is served by the Children's Mercy Comprehensive Epilepsy Monitoring Unit (EMU) in Overland Park, Kansas. Subjects will be identified from these EMU patient population. Those meeting inclusion criteria will be approached for possible enrollment. Inclusion criteria will be defined by patients that were diagnosed with focal CSWS in accordance with the ILAE classification with SWI \>85% during NREM sleep on their previous or most recent EEG. Patients and their parents/guardians will provide assent/consent for participation in the study after being briefed on the nature of the study, by reading and signing assent and assent/consent forms, respectively

Multisite Transcranial Magnetic Stimulation (mTMS) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Migraines
• Smoking Cessation

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Migraines

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Who Is Running the Clinical Trial?

Children's Mercy Hospital Kansas City

Lead Sponsor

Trials

261

Recruited

941,000+

Cornell University

Collaborator

Trials

179

Recruited

14,090,000+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Published Research Related to This Trial

In a study of five patients with intractable epilepsy, three months of low-frequency repetitive transcranial magnetic stimulation (rTMS) treatment led to a significant overall reduction in mean daily number of seizures (MDNS) by 22.8%, indicating some efficacy of this treatment.

The most notable improvement was observed in a patient with focal cortical dysplasia, who experienced a 43.09% reduction in seizures, suggesting that rTMS may be particularly beneficial for patients with specific types of brain lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental therapy of epilepsy with transcranial magnetic stimulation: lack of additional benefit with prolonged treatment. Brasil-Neto, JP., de Araújo, DP., Teixeira, WA., et al.[2019]

Transcranial magnetic stimulation (TMS) is a non-invasive technique that has evolved to have therapeutic applications, including the suppression of cortical hyperexcitability in drug-resistant epilepsies.

While the current evidence suggests that repetitive TMS has limited therapeutic effects in epilepsy, the review highlights the need for further clinical testing to explore its potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for drug-resistant epilepsies: rationale and clinical experience. Kimiskidis, VK.[2010]

Transcranial magnetic stimulation (TMS) has a very low seizure risk, with only 0.08 seizures reported per 1,000 sessions, and less than 0.02 seizures per 1,000 sessions when guidelines are followed for individuals without known risk factors.

The study found that exceeding safety guidelines increases the risk of seizures, and seizures are more likely to occur during the first few TMS sessions, suggesting that TMS is generally safe when administered properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Lerner, AJ., Wassermann, EM., Tamir, DI.[2021]

Repetitive transcranial magnetic stimulation (rTMS) has a low risk of inducing seizures in patients with epilepsy, with only a 1.4% incidence of seizures reported during treatment, primarily linked to low-frequency rTMS.

The majority of adverse events associated with rTMS were mild, with headaches being the most common, occurring in 9.6% of subjects, indicating that rTMS is generally safe and tolerable for individuals with epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: a review of the literature. Bae, EH., Schrader, LM., Machii, K., et al.[2007]

Transcranial magnetic stimulation (TMS) has been shown to identify changes in cortical excitability linked to specific epilepsy syndromes, which could help in diagnosing and understanding epilepsy better.

TMS may also serve as a valuable biomarker for predicting responses to treatments and has potential therapeutic applications for drug-resistant epilepsies, especially as stimulation techniques are optimized.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for the diagnosis and treatment of epilepsy. Kimiskidis, VK., Valentin, A., Kälviäinen, R.[2014]

Low frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to significantly reduce seizure frequency in patients with medically intractable epilepsy, with an overall effect size of 0.34 based on a review of 11 studies involving 164 participants.

The treatment is particularly effective for patients with neocortical epilepsy or cortical dysplasia, showing a higher effect size of 0.71, indicating that the underlying cause of epilepsy can influence the efficacy of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiepileptic effects of low frequency repetitive transcranial magnetic stimulation: A meta-analysis. Hsu, WY., Cheng, CH., Lin, MW., et al.[2011]

Transcranial magnetic stimulation (TMS) appears to be a safe treatment for individuals with drug-resistant epilepsy, with few adverse effects reported, such as headache and dizziness.

While some studies showed a significant reduction in seizure frequency (up to 78.9%), the overall evidence for the efficacy of TMS in reducing seizures is inconclusive due to variability in study designs and outcomes, although it may effectively reduce epileptiform discharges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for the treatment of epilepsy. Chen, R., Spencer, DC., Weston, J., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that has shown potential for treating epilepsy, but its effectiveness remains unclear based on conflicting results from clinical trials.

Despite the uncertainty regarding its therapeutic efficacy in refractory epilepsy, the non-invasive nature of rTMS suggests it is worth exploring further as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for the treatment of refractory epilepsy. Carrette, S., Boon, P., Dekeyser, C., et al.[2022]

Low frequency repetitive transcranial magnetic stimulation (rTMS) is being explored as a non-invasive treatment option for patients with intractable epilepsy, which means their seizures are difficult to control with standard medications.

This approach could provide a new avenue for managing epilepsy, potentially improving the quality of life for those who do not respond well to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New adjunctive therapy for intractable epilepsy. [2019]

Repetitive transcranial magnetic stimulation (rTMS) has a low risk of inducing seizures in patients with epilepsy, with a crude per subject seizure risk of only 2.9% based on an analysis of 426 subjects.

The majority of adverse events reported (18.3%) were mild, with headaches and dizziness being the most common, indicating that rTMS is generally safe and tolerable for patients with epilepsy, similar to its use in other populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of repetitive transcranial magnetic stimulation in patients with epilepsy: A systematic review. Pereira, LS., Müller, VT., da Mota Gomes, M., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has not been thoroughly studied for side effects, with the main known risk being the acute production of seizures.

While tissue damage from rTMS is unlikely, there are concerns about potential cognitive effects and the possibility of long-term changes in brain function that have not yet been fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of repetitive transcranial magnetic stimulation. Wassermann, EM.[2005]

A single session of repetitive transcranial magnetic stimulation (rTMS) effectively reduced epileptiform activity in two patients with epilepsy, as indicated by decreased brain perfusion in the targeted area after treatment.

One patient experienced a significant reduction in seizure frequency, with seizures becoming intermittent and stopping within 24 hours, while the other showed only minimal improvement, highlighting the need for further research to confirm these findings in a larger group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rTMS reduces focal brain hyperperfusion in two patients with EPC. Graff-Guerrero, A., Gonzáles-Olvera, J., Ruiz-García, M., et al.[2019]

In a study involving 43 patients with drug-resistant epilepsy, slow repetitive transcranial magnetic stimulation (rTMS) did not significantly reduce seizure frequency compared to a placebo, indicating limited efficacy as an adjunctive treatment.

However, rTMS did lead to a significant decrease in interictal EEG epileptiform abnormalities in about one-third of the patients, suggesting a potential biological effect that could inform future noninvasive neuromodulatory treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slow repetitive TMS for drug-resistant epilepsy: clinical and EEG findings of a placebo-controlled trial. Cantello, R., Rossi, S., Varrasi, C., et al.[2007]

In a study involving 8 patients with refractory epilepsy and malformations of cortical development, low-frequency repetitive transcranial magnetic stimulation (rTMS) significantly reduced epileptiform discharges in EEG by 46.4% and 42.1% at 15 and 30 days post-treatment, respectively.

The treatment also led to a notable decrease in seizure frequency, with reductions of 57.3% and 51.2% over the same time periods, indicating rTMS may be an effective therapeutic option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiepileptic effects of repetitive transcranial magnetic stimulation in patients with cortical malformations: an EEG and clinical study. Fregni, F., Thome-Souza, S., Bermpohl, F., et al.[2007]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04034030

Study Details | NCT04034030 | Repeated Oscillatory TMS ...

The investigators are investigating the effectiveness of a wearable multisite transcranial magnetic stimulation (mTMS) device that can deliver stimuli at ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40782718/

Repetitive transcranial magnetic stimulation for the ...

LF rTMS targeting the epileptogenic focus appears to be a safe and potentially effective non-invasive adjunctive therapy for focal DRE.

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40336040/

protocol for a multi-site, double-blind, randomized controlled trial

The study is a double-blind, sham-controlled trial seeking to recruit 160 participants with a current moderate to severe CcUD or MtUD diagnosis.

4.

withpower.com

withpower.com/trial/phase-7-2019-e3c44

TMS Therapy for Epilepsy

A single session of repetitive transcranial magnetic stimulation (rTMS) effectively reduced epileptiform activity in two patients with epilepsy, as indicated by ...

5.

ctv.veeva.com

ctv.veeva.com/study/repeated-oscillatory-tms-therapy-of-the-epileptogenic-cortical-area-in-children-with-focal-csws

Repeated Oscillatory TMS Therapy of the Epileptogenic ...

The investigators are investigating the effectiveness of a wearable multisite transcranial magnetic stimulation (mTMS) device that can ...