Focused Ultrasound for Epilepsy

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

10 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment MRgFUS for epilepsy?

MRgFUS is a noninvasive treatment that has shown promise in treating drug-resistant epilepsy by targeting specific brain areas with focused ultrasound, potentially reducing the need for more invasive surgeries. It has been used successfully for other conditions like bone metastases and uterine fibroids, suggesting its potential effectiveness for epilepsy as well. ^{1 2 3 4 5}

Is focused ultrasound generally safe for humans?

Focused ultrasound, also known as MRgFUS, has been explored for various conditions, including epilepsy and breast cancer. It is considered a promising non-invasive treatment with fewer risks compared to traditional surgery, but more studies are needed to fully understand its safety and effectiveness. ^{1 2 3 4 6}

How is the MRgFUS treatment for epilepsy different from other treatments?

MRgFUS (Magnetic Resonance-guided Focused Ultrasound) is a unique, noninvasive treatment that uses focused sound waves to target and treat specific areas in the brain without needing surgery. Unlike traditional surgical options, it avoids risks like infection and long recovery times, and it can be precisely guided using real-time imaging to treat drug-resistant epilepsy. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of this study is to assess the safety and feasibility of Magnetic Resonance Imaging-guided focused ultrasound (MRgFUS) in patients with epilepsy whose medicines are not working well. The ExAblate (ExAblate) transcranial system is the name of the device that will be used to create and send ultrasound waves through the scalp and skull precisely to a small structure located in the center of the brain. This structure is known as the "Anterior Nucleus", and is an important region in the brain that may cause the seizures. Safety will be measured by recording and analyzing any adverse effects that may occur from the day of the experimental surgery through 12 months following the surgery.

Research Team

Vibhor Krishna, MD SM

Principal Investigator

University of North Carolina, Chapel Hill

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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 MR guides 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 up to an additional 7 participants 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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound for mesial temporal lobe epilepsy: a case report. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

MR-Guided Focused Ultrasound for Refractory Epilepsy: Where Are We Now? [2023]

3. United States 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. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound surgery using an enhanced sonication technique in a pig muscle model. [2019]

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

Intracranial applications of magnetic resonance-guided focused ultrasound. [2021]

6. Germany 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. [2020]