Focused Ultrasound for Epilepsy

Recruiting at 2 trial locations

Overseen By Arthur Lung, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: NaviFUS Corporation

Must be taking: Anti-epileptic drugs

Disqualifiers: Generalized epilepsy, Brain tumor, others

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

Compensation: Varies

Number of Visits: 7

Duration: 3 weeks

8 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You will need to be on a stable regimen of your current anti-epileptic drugs for at least 30 days before joining the trial, but you can continue taking them during the study. Rescue benzodiazepines or occasional extra doses of ongoing medicines are allowed as needed.

What data supports the effectiveness of the treatment Low-intensity Focused Ultrasound Neuromodulation for epilepsy?

Research shows that low-intensity focused ultrasound (LIFUS) can safely and non-invasively target brain areas to help control seizures in animal models of epilepsy without damaging tissue. This treatment is being studied for its potential to help people with drug-resistant epilepsy who cannot have surgery. ^{1 2 3 4 5}

Is focused ultrasound safe for treating epilepsy?

Focused ultrasound, including low-intensity focused ultrasound (LIFUS), has been studied for its safety in both animals and humans. Research shows it can target brain areas without causing damage, and studies in epilepsy patients have not shown harmful changes in brain tissue after treatment. ^{2 3 4 5 6}

How does the treatment Low-intensity Focused Ultrasound Neuromodulation differ from other treatments for epilepsy?

Low-intensity Focused Ultrasound Neuromodulation is unique because it is a non-invasive treatment that uses sound waves to target specific brain areas without surgery or radiation. Unlike traditional treatments that may involve medication or invasive procedures, this method can modulate brain activity to reduce seizures without damaging tissue. ^{2 3 4 5 7}

What is the purpose of this trial?

This will be a prospective, open-label, single-arm, multi-center, pilot study to evaluate the safety, tolerability, and preliminary efficacy of low-intensity focused ultrasound (LIFU) neuromodulation using NaviFUS System in patients with drug-resistant unilateral or bilateral temporal lobe epilepsy (DR-TLE).

Eligibility Criteria

Adults over 18 with drug-resistant temporal lobe epilepsy who've tried at least two anti-epileptic drugs without success. Participants must have had regular seizures despite medication, be able to complete questionnaires in English, and consent to shave their head for treatment application. Pregnant women or those with electronic brain implants, severe psychiatric conditions, or recent substance abuse are excluded.

Inclusion Criteria

Patients with the central of FUS exposure region are located at least 30 mm distance beneath the skull bone

My epilepsy has not improved despite trying two different medications.

MRI and EEG within the past 3 years. At least one prior EEG should demonstrate interictal or ictal focal epileptiform findings

Exclusion Criteria

Patients have received an investigational drug or an investigational device within 4 weeks prior to the first treatment

I have epilepsy that affects all parts of my brain or have had seizures not caused by epilepsy.

Implanted electronic device, for example, implanted cardioverter-defibrillator (ICD), cardiac pacemaker, permanent medication pumps, cochlear implants, responsive neurostimulator, deep brain stimulation (DBS), or other electronic devices implanted in the brain. If a patient has a working Vagus Nerve Stimulator (VNS) in place, the settings should remain stable throughout the trial and the device will be turned off prior to each sonication treatment and then turned back on afterward

Timeline

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

1 visit (in-person or virtual)

Baseline Observation

Participants maintain an 8-week seizure diary to establish baseline data

8 weeks

Ongoing diary entries

Treatment

Participants receive 6 FUS treatments over 3 consecutive weeks

3 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Regular follow-up visits

Treatment Details

Interventions

• Low-intensity Focused Ultrasound Neuromodulation

Trial Overview The trial is testing the safety and initial effectiveness of a new technique called low-intensity focused ultrasound (LIFU) neuromodulation using the NaviFUS System on patients with drug-resistant epilepsy. It's an open-label study where all participants receive the experimental treatment.

Participant Groups

Group I: FUS treatment Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

NaviFUS Corporation

Lead Sponsor

Trials

10

Recruited

120+

NaviFUS US LLC

Collaborator

Trials

2

Recruited

20+

Findings from Research

Low-intensity, pulsed focused ultrasound (FUS) significantly reduced the occurrence of epileptic EEG bursts in a rat model of epilepsy, indicating its potential efficacy in suppressing seizure activity.

The FUS treatment was non-invasive and did not cause any damage to brain tissue, suggesting it could be a safe alternative for treating epilepsy without the risks associated with invasive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity. Min, BK., Bystritsky, A., Jung, KI., et al.[2022]

Low intensity focused ultrasound (LIFUS) is a promising noninvasive treatment for drug-resistant epilepsy (DRE), showing potential to suppress seizures without damaging brain tissue, as demonstrated in preclinical studies and initial trials in humans.

LIFUS can precisely target specific brain regions, making it a novel alternative to traditional electrostimulatory devices, which are often palliative and not suitable for all patients, thus expanding treatment options for those with DRE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Intensity Focused Ultrasound for Epilepsy- A New Approach to Neuromodulation. Bubrick, EJ., McDannold, NJ., White, PJ.[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]

Focused ultrasound (FUS) can be safely applied to the seizure onset zone in patients with drug-resistant epilepsy, with no significant adverse effects like brain lesions or edema observed in the six patients studied.

While two patients experienced a decrease in seizure frequency after FUS treatment, one patient had an increase in subclinical seizures, indicating that further research with a larger cohort is needed to better understand the efficacy and optimal parameters for FUS in seizure control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of focused ultrasound for drug-resistant epilepsy. Lee, CC., Chou, CC., Hsiao, FJ., et al.[2022]

Focused ultrasound ablation (FUSA) of the anterior nucleus of the thalamus (ANT) is a promising treatment for patients with treatment-refractory epilepsy, showing significant reduction in seizure frequency in a pilot study of two adult subjects.

The procedure was well-tolerated with no serious adverse events, although one patient experienced a decline in certain cognitive functions, highlighting the need for careful monitoring of potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 open-label trial evaluating focused ultrasound unilateral anterior thalamotomy for focal onset epilepsy. Krishna, V., Mindel, J., Sammartino, F., et al.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

Therapeutic ultrasound: The future of epilepsy surgery? [2022]

2. England pubmed.ncbi.nlm.nih.gov

Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity. [2022]

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

Low Intensity Focused Ultrasound for Epilepsy- A New Approach to Neuromodulation. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Pilot study of focused ultrasound for drug-resistant epilepsy. [2022]

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

A phase 1 open-label trial evaluating focused ultrasound unilateral anterior thalamotomy for focal onset epilepsy. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Different Modes of Low-Frequency Focused Ultrasound-Mediated Attenuation of Epilepsy Based on the Topological Theory. [2021]