Low-intensity focused ultrasound treatment for drug-resistant epilepsy

A Prospective, Open-label, Single-arm, Multi-center, Pilot Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Low-intensity Focused Ultrasound Neuromodulation in Patients With Drug-resistant Unilateral or Bilateral Temporal Lobe Epilepsy

This study is testing if low-intensity focused ultrasound can help people with drug-resistant temporal lobe epilepsy have fewer seizures while they continue taking their regular medications.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 8 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: NaviFUS Corporation (industry)
• Locations: 3 sites (Palo Alto, California and 2 other locations)
• Trial ID: NCT06388707 on ClinicalTrials.gov

What this trial studies

This pilot study evaluates the safety, tolerability, and preliminary efficacy of low-intensity focused ultrasound (LIFU) neuromodulation using the NaviFUS System in patients with drug-resistant temporal lobe epilepsy (DR-TLE). It involves a prospective, open-label, single-arm design with a maximum enrollment of 8 patients. Participants will undergo a 2-month baseline observation period followed by 6 ultrasound treatments over 3 weeks, with a 12-week follow-up to assess seizure frequency and treatment effects. Patients may continue their anti-seizure medications throughout the study.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with drug-resistant temporal lobe epilepsy who have not responded to at least two anti-epileptic drug regimens.

Not a fit: Patients with epilepsy that is not drug-resistant or those with seizure types outside of focal-onset seizures may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new non-invasive option for patients with drug-resistant epilepsy, potentially reducing seizure frequency.

How similar studies have performed: While focused ultrasound is a novel approach in this context, similar neuromodulation techniques have shown promise in other neurological conditions, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

1. Male or female patients ≥ 18 years of age at the time of enrollment.
2. Patients with drug-resistant temporal lobe epilepsy (DR-TLE), defined as failure of adequate trials of two tolerated, appropriately chosen and used anti-epileptic drug schedules (whether as monotherapies or in combination).
3. Focal-onset seizures with or without secondary generalization and no more than two known seizure onset zones (seizure foci), at least one which is in the mesial temporal lobe.
4. At least 4 focal-onset seizures with objectively visible or significantly disabling manifestations in the 8-week baseline and at least one seizure per month in the baseline.
5. MRI and EEG within the past 3 years. At least one prior EEG should demonstrate interictal or ictal focal epileptiform findings.
6. Patients with the central of FUS exposure region are located at least 30 mm distance beneath the skull bone.
7. Patients must be on a stable regimen of anti-epileptic drugs (AEDs) for at least 30 days at the time of enrollment, except for rescue benzodiazepines or occasional extra doses of ongoing medicines, as required.
8. Females of childbearing potential must have a negative pregnancy test prior to the first treatment. Females of childbearing potential and male patients with a partner of childbearing potential must agree to follow acceptable method of contraception (as outlined below) from prior to the first study treatment to 3 months after the last study treatment. Standard acceptable methods include use of highly effective method of contraception, including: hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, spermicide, vasectomy, intrauterine device, and abstinence from sex.
9. Patients are able and willing to have their hair shaved in the region where the coupling membrane will touch (or if they prefer, whole head).
10. Patients are able to complete all clinical trial-related questionnaires in English, including with the use of a suitable interpreter.
11. Patients or their legal representatives are able to provide written informed consent for participation in the trial and comply with study requirements in the opinion of the Investigator during the study period.

Exclusion Criteria:

1. Patients who have primary generalized epilepsy, mixed focal and generalized epilepsy, or any history of non-epileptic seizures.
2. Patients who have experienced tonic-clonic status epilepticus in the 12 months before the time of enrollment in the study. Subjects with focal status epilepticus may be considered at the discretion of the Investigator.
3. The only feasible sonication pathway to the seizure onset zones involves either:

   1. Skull area is covered by previous surgical site(s), scars, scalp disorders (e.g., eczema, psoriasis), or scalp atrophy.
   2. Clips or other metallic implanted objects in the skull or brain, except shunts.
   3. A prior craniotomy site.
4. Patients with a potentially acute or progressive neurologic disorder (e.g., brain tumor, multiple sclerosis, dementia, or intracranial vascular lesion).
5. 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.
6. Patients with severe depression, active suicidal ideation or behavior (as per the C-SSRS), active psychosis (excluding time-limited postictal psychosis), or psychiatric hospitalization in the year before time of enrollment.
7. Patient has an IQ \< 70, based on the Wechsler Abbreviated Scale of Intelligence (WASI-II or other Wechsler IQ measure).
8. Coexisting medical problems of sufficient severity to limit compliance with or interpretation of the study.
9. Patients have received an investigational drug or an investigational device within 4 weeks prior to the first treatment.
10. Radiofrequency thermocoagulation (RFTC) within 2 months before time of enrollment.
11. Known history of substance or alcohol abuse within the past year, not counting marijuana.
12. Pregnant or breast-feeding women.
13. Any other condition that, in the Investigator's judgment, might affect study endpoints or might increase the risk to the patients or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.

Where this trial is running

Palo Alto, California and 2 other locations

• Stanford University School of Medicine — Palo Alto, California, United States (RECRUITING)
• Brigham and Women's Hospital — Boston, Massachusetts, United States (RECRUITING)
• University of Virginia School of Medicine — Charlottesville, Virginia, United States (RECRUITING)

Study contacts

• Study coordinator: Sheang-Tze Fung, Ph.D.

Conditions: Drug Resistant Epilepsy, Epilepsy, Seizures, Focal, Seizure, Seizure Disorder, NaviFUS System, Focused Ultrasound, Low-Intensity Focused Ultrasound