Focused Ultrasound for Epilepsy

Not currently recruiting at 1 trial location

Overseen By Heather L Ward, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ohio State University

Must be taking: Anti-epileptic drugs

Disqualifiers: Low seizure frequency, Vagal nerve stimulator, Untreated neuropsychiatric disorders, Recent substance abuse, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat epilepsy using focused ultrasound waves to target the Anterior Nucleus, a specific brain area potentially responsible for seizures. The goal is to determine if this approach, known as MRgFUS (Magnetic Resonance-guided Focused Ultrasound), is safe and can effectively create a small, controlled lesion in the brain to reduce seizures. It is intended for adults with epilepsy who have tried at least two medications without success and experience frequent seizures, at least three per month. Participants must maintain a detailed seizure diary and have an MRI showing the target brain area. As an unphased trial, this study offers patients the chance to contribute to pioneering research that could lead to new treatment options for epilepsy.

Will I have to stop taking my current medications?

The trial requires that participants have a stable medication dosage for 3 months before enrollment and maintain it for 3 months after treatment. This suggests you will not need to stop your current medications, but you must keep the dosage unchanged during these periods.

What prior data suggests that this device is safe for treating epilepsy?

Research has shown that focused ultrasound treatments, like the one under study for epilepsy, are generally safe. Previous studies found that patients usually tolerate this method well. For instance, the FDA has approved high-intensity focused ultrasound for other conditions, indicating a certain level of safety.

Side effects are usually mild and temporary, such as headaches or dizziness, and often resolve on their own. However, most current evidence pertains to short-term effects, and long-term safety remains under investigation.

This treatment uses sound waves to target a specific part of the brain involved in seizures. While still under study, early results appear promising. Participants in other trials have generally responded well to the procedure, but individual experiences can vary. It is important to discuss potential risks and benefits with the trial team and your doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about MRgFUS, or Magnetic Resonance-guided Focused Ultrasound, for epilepsy because it offers a non-invasive alternative to traditional surgical approaches like resective surgery or laser ablation. Unlike these methods, MRgFUS uses sound waves to target and treat specific areas of the brain without needing to make any incisions. This precision reduces the risk of infection and may lead to quicker recovery times. Additionally, it allows for real-time monitoring during the procedure, potentially improving safety and effectiveness.

What evidence suggests that the ExAblate device is effective for epilepsy?

Research has shown that high-intensity focused ultrasounds (HIFU) are becoming a promising method for managing focal drug-resistant epilepsy. In this trial, participants will undergo unilateral focused ultrasound thalamotomy targeting the anterior nucleus, a small area in the brain, which may help stop seizures. Previous studies found that many patients experienced freedom from seizures after this treatment. Although results vary, this technique's ability to reduce seizure frequency is gaining attention. This non-invasive method offers hope for those whose medications are ineffective. ^{1 2 3 6 7}

Who Is on the Research Team?

Vibhor Krishna, MD, SM

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

This trial is for people with epilepsy whose seizures aren't controlled by medication. They must have focal onset seizures that can generalize, no recent substance abuse, and a stable medication dose for the last 3 months. Participants need an identifiable Anterior Nucleus on MRI, agree to keep a seizure diary, and not be pregnant or using ineffective birth control.

Inclusion Criteria

The MRI shows that the Anterior Nucleus (AN) can be seen clearly on the pictures.

I have had 3 or more seizures a month in the last 3 months.

My medication doses have been the same for the last 3 months.

Exclusion Criteria

You have had a bad reaction to IV dye or contrasting agents in the past.

Your score on a specific test for thinking and problem-solving is less than 70.

I have epilepsy caused by a previous herpes infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants undergo unilateral MR-guided focused ultrasound thalamotomy targeting the anterior nucleus

1 day

1 visit (in-person)

Initial Follow-up

Participants are monitored for safety and effectiveness, with data reviewed by the DSMC

3 months

Monthly visits (in-person)

Extended Follow-up

Participants continue to be monitored for safety and effectiveness, including seizure frequency and quality of life assessments

9 months

Visits at months 6 and 12 (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• MRgFUS

Trial Overview The study tests the safety of using focused ultrasound (MRgFUS) to target the brain's Anterior Nucleus in patients with epilepsy. The ExAblate transcranial system delivers these waves non-invasively through the skull to potentially prevent seizures.

How Is the Trial Designed?

Group I: high intensity focused ultrasound Experimental Treatment 1 Intervention

Initially, 3 patients will be enrolled and followed for 3 months to assess the safety of study intervention which is unilateral focused ultrasound thalamotomy (anterior nucleus). These data will be reviewed by the Data and Safety Monitoring Committee (DSMC) and the FDA. If approval is granted by the DSMC and FDA, then additional subjects will be enrolled.

MRgFUS is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as ExAblate for:

• Essential Tremor
• Tremor Dominant Idiopathic Parkinson’s Disease
• Neuropathic Pain
• Pain Palliation of Metastatic Bone Cancer
• Treatment of Uterine Fibroids

Approved in United States as ExAblate for:

• Unilateral Thalamotomy treatment of idiopathic Essential Tremor patients with medication-refractory tremor

Approved in Canada as ExAblate for:

• Pain Palliation of Metastatic Bone Cancer
• Treatment of Uterine Fibroids

Approved in Japan as ExAblate for:

• Pain Palliation of Metastatic Bone Cancer
• Treatment of Uterine Fibroids

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

Vibhor Krishna

Lead Sponsor

Trials

4

Recruited

50+

Focused Ultrasound Foundation

Collaborator

Trials

18

Recruited

460+

Published Research Related to This Trial

This case report presents the first use of transcranial magnetic resonance-guided focused ultrasound (MRgFUS) for treating mesial temporal lobe epilepsy (MTLE), showing promising results as the patient remained almost seizure-free for up to 12 months after the procedure.

Despite challenges in achieving high ablation temperatures due to technical limitations, the findings suggest that MRgFUS could be a safe and feasible treatment option for MTLE, warranting further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound for mesial temporal lobe epilepsy: a case report. Abe, K., Yamaguchi, T., Hori, H., et al.[2020]

Magnetic resonance-guided focused ultrasound (MRgFUS) is a promising noninvasive technique for disrupting seizure circuits in patients with mesial temporal lobe epilepsy (MTLE), potentially reducing the risks associated with traditional surgical options.

In a study involving 10 patients, MRgFUS planning successfully identified safe ablation targets while maintaining an average separation of 8.5 mm from critical optic pathways, which could help prevent visual deficits post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound for ablation of mesial temporal epilepsy circuits: modeling and theoretical feasibility of a novel noninvasive approach. Parker, WE., Weidman, EK., Chazen, JL., et al.[2022]

MR-guided focused ultrasound (MRgFUS) is emerging as a promising minimally invasive treatment for drug-resistant epilepsy, offering potential benefits such as thermoablation and neuromodulation without the risks associated with traditional surgical methods.

Current studies suggest that high-intensity ultrasound may effectively target lesions in the anterior thalamus, while low-intensity ultrasound could modulate the hippocampus, but further research is needed to ensure these strategies are safe and effective for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR-Guided Focused Ultrasound for Refractory Epilepsy: Where Are We Now? Labate, A., Bertino, S., Morabito, R., et al.[2023]

The first clinical experience with MRgFUS using the ExAblate 2100 system for non-invasive breast cancer showed promising results, with no severe adverse events reported in two patients.

Pathological examinations indicated that the treatment effectively induced tumor necrosis, suggesting that MRgFUS is a safe and feasible option for non-invasive breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative use of magnetic resonance imaging-guided focused ultrasound surgery for non-invasive breast cancer: a report of two cases. Matsutani, A., Ide, Y., Miura, S., et al.[2020]

The study demonstrated that enhanced magnetic resonance-guided focused ultrasound (MRgFUS) can create ablations that are, on average, 1.8 times larger than those produced by standard sonication using the same energy, indicating improved efficacy.

The enhanced MRgFUS method was found to be safe and controllable, with predictable ablation locations and consistent thermal damage patterns, suggesting it could significantly shorten tumor ablation procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound surgery using an enhanced sonication technique in a pig muscle model. Kopelman, D., Inbar, Y., Hanannel, A., et al.[2019]

Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive technique that can precisely target and treat brain disorders by creating thermal lesions and disrupting the blood-brain barrier, which is a significant advancement in neurotherapeutics.

MRgFUS has been successfully used in various clinical applications, including treating bone metastases and uterine fibroids, and is being explored as a safer alternative to traditional neurosurgery for a range of brain-related conditions, supported by studies from small animal models to large clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial applications of magnetic resonance-guided focused ultrasound. Lipsman, N., Mainprize, TG., Schwartz, ML., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10672423/

MR-Guided Focused Ultrasound for Refractory Epilepsy Despite the high heterogeneity across studies, especially regarding surgical procedures, a high rate of seizure freedom was observed after ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0035378723011451

Focused ultrasounds: What is their future in epileptology? ... High intensity focused ultrasounds (HIFU) are being increasingly advocated as a useful tool in the management of focal drug-resistant epilepsy.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04526262

Study Details | NCT04526262 | Assessment of Initial ... The proposed study is to evaluate initial efficacy and safety of the BBB disruption with transcranial MRI-guided focused ultrasound (ExAblate 4000 type 2.0) in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8137896/

Outcome and Complications of MR Guided Focused ... MRgFUS for ET seems to be an effective procedure for relieving unilateral tremor. Use of DTI based targeting revealed a significant reduction in post procedure ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05032105

Study Details | NCT05032105 | The Impact of Focused ... The purpose of this study is to evaluate the feasibility, safety, and effects on anxiety of high intensity focused ultrasound ablation (FUSA) in patients ...

6. karger.com karger.com/doi/10.1159/000545716

Focused Ultrasound in the Treatment of Epilepsy Evaluate feasibility, safety, and effects on anxiety of high intensity focused ultrasound ablation (FUSA) in patients suffering from ...

7. anthem.com anthem.com/medpolicies/abc/active/mp_pw_a050053.html

MED.00057 MRI Guided High Intensity Focused ... The evidence regarding bilateral MRgFUS is in the early stages and is limited to short-term outcomes with no data on long-term safety. The current evidence ...