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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for temporal lobe epilepsy that does not respond to medication. The treatment uses low-intensity focused ultrasound, a non-invasive technique targeting the brain. The goal is to determine if this method is safe, tolerable, and effective in reducing seizures. Suitable participants have temporal lobe epilepsy, have tried at least two medications without success, and experience at least one significant seizure per month. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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 prior data suggests that this focused ultrasound technique is safe for epilepsy patients?

Earlier studies have shown that low-intensity focused ultrasound (LIFU) holds potential as a safe treatment for epilepsy. Research suggests that LIFU can reduce seizures in animals without causing harm. In human studies, this technology has been used safely for brain treatments, with no serious side effects reported when used correctly.

Although limited data exists on LIFU for epilepsy in humans, the treatment is generally well-tolerated, meaning most people do not experience severe side effects. The treatment is non-invasive, requiring neither surgery nor radiation, which can be safer for patients.

As this study is in its early stages, safety remains a primary focus. Researchers are closely monitoring participants for any health changes. Overall, LIFU appears promising as a safe option for those with epilepsy that doesn't respond to medication. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for epilepsy?

Researchers are excited about low-intensity focused ultrasound neuromodulation for epilepsy because it offers a non-invasive approach to treatment. Unlike traditional methods such as anti-seizure medications or surgery, this technique uses ultrasound waves to target and modulate specific brain areas involved in seizures without needing incisions or long recovery times. This innovative mechanism of action could potentially reduce side effects and provide relief for patients who do not respond well to existing treatments.

What evidence suggests that low-intensity focused ultrasound neuromodulation might be an effective treatment for epilepsy?

Research has shown that low-intensity focused ultrasound (LIFU), which participants in this trial will receive, could be a promising treatment for epilepsy, especially for those who don't respond to medication. In animal studies, LIFU safely reduced seizure activity. Early studies with humans showed significant decreases in epileptic bursts after treatment. These findings suggest that LIFU might effectively manage seizures without surgery or radiation. Overall, the evidence supports LIFU's potential to help people with drug-resistant epilepsy. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9684587/

Low Intensity Focused Ultrasound for Epilepsy Low intensity focused ultrasound is a promising, novel, incisionless, and radiation-free alternative form of neuromodulation being investigated for epilepsy.

2. fusfoundation.org fusfoundation.org/posts/low-intensity-focused-ultrasound-neuromodulation-for-epilepsy/

Low-Intensity Focused Ultrasound Neuromodulation for ... In a wide variety of preclinical studies, LIFUS safely suppressed seizure activity in epilepsy animal models. In human studies, when researchers ...

3. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.886584/full

Recent Advances in the Use of Focused Ultrasound as a ... Results showed that epileptic bursts were significantly reduced after the first period of sonication, and even further decreased after the second sonication.

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/93/NCT03868293/Prot_SAP_000.pdf

Low Intensity Focused Ultrasound Treatment for Drug- ... Approximately 67% of patients with epilepsy achieve seizure control with antiepileptic drugs, leaving 33% of patients with persisting seizures despite ...

5. neuromodulationjournal.org neuromodulationjournal.org/article/S1094-7159(24)00784-0/fulltext

IS062 LOW INTENSITY FOCUSED ULTRASOUND FOR ... The seizure-suppressive effect of LIFU-induced neuromodulation has been studied in several clinical and preclinical trials, showing promising results (Chen et ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X21001224

Safety of focused ultrasound neuromodulation in humans ... This study supports the hypothesis that low-intensity Transcranial Focused Ultrasound (tFUS) used for neuromodulation of brain circuits at intensities up to ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9599299/

Safety of Clinical Ultrasound Neuromodulation - PMC For clinical applications, TPS has been shown to be safe, when sticking to our published patient protocols and exclusion/inclusion criteria, such as no signs of ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06388707?cond=Temporal%20branch&viewType=Table&rank=8

Study Details | A Safety, Tolerability, and Preliminary ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...