A Safety, Tolerability, and Preliminary Efficacy of Low-intensity Focused Ultrasound Neuromodulation in Patients With Drug-resistant Epilepsy

NCT06388707 | Recruiting Phase 1 FDA Device

• 1 other identifier: NF-2022-01
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

Brief Summary

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).

Conditions

Drug Resistant Epilepsy; Epilepsy; Seizures, Focal; Seizure; Seizure Disorder

Keywords

NaviFUS System; Focused Ultrasound; Low-Intensity Focused Ultrasound; LIFU

Outcome Measures

Primary Outcomes (1)

• Adverse events (AEs)

  The incidence and severity of AEs associated with LIFU neuromodulation in patients with drug-resistant unilateral or bilateral temporal lobe epilepsy.

  up to 23 weeks

Secondary Outcomes (6)

• Change from baseline in seizure frequency

  up to 23 weeks

• Change from baseline in electroencephalography (EEG) epileptiform discharges

  up to 15 weeks

• Days of seizure-free

  up to 23 weeks

• Changes from baseline in Beck Anxiety Inventory (BAI)

  up to 23 weeks

• Changes from baseline in Beck Depression Inventory (BDI-II)

  up to 23 weeks

Other Outcomes (1)

• Change from baseline in subjective seizure strength

  up to 23 weeks

Study Arms (1)

FUS treatment

EXPERIMENTAL

Device: NaviFUS System

Interventions

NaviFUS System DEVICE

FUS treatment will be conducted with following exposure parameters: intracranial spatial-peak temporal-average intensity (ISPTA) ceiling level: 2.8 W/cm2, burst length: 3 ms, duration: max. three consecutive 10-minute FUS exposures with two 5-minute intermission intervals.

FUS treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 18 years of age at the time of enrollment.
• 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).
• 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.
• 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.
• MRI and EEG within the past 3 years. At least one prior EEG should demonstrate interictal or ictal focal epileptiform findings.
• Patients with the central of FUS exposure region are located at least 30 mm distance beneath the skull bone.
• 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.
• 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.
• 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).
• Patients are able to complete all clinical trial-related questionnaires in English, including with the use of a suitable interpreter.
• 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.

You may not qualify if:

• Patients who have primary generalized epilepsy, mixed focal and generalized epilepsy, or any history of non-epileptic seizures.
• 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.
• The only feasible sonication pathway to the seizure onset zones involves either:
• Skull area is covered by previous surgical site(s), scars, scalp disorders (e.g., eczema, psoriasis), or scalp atrophy.
• Clips or other metallic implanted objects in the skull or brain, except shunts.
• A prior craniotomy site.
• Patients with a potentially acute or progressive neurologic disorder (e.g., brain tumor, multiple sclerosis, dementia, or intracranial vascular lesion).
• 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.
• 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.
• Patient has an IQ \< 70, based on the Wechsler Abbreviated Scale of Intelligence (WASI-II or other Wechsler IQ measure).
• Coexisting medical problems of sufficient severity to limit compliance with or interpretation of the study.
• Patients have received an investigational drug or an investigational device within 4 weeks prior to the first treatment.
• Radiofrequency thermocoagulation (RFTC) within 2 months before time of enrollment.
• Known history of substance or alcohol abuse within the past year, not counting marijuana.
• Pregnant or breast-feeding women.

Sponsors & Collaborators

• NaviFUS Corporation: lead
• NaviFUS US LLC: collaborator

Study Sites (3)

Stanford University School of Medicine

Palo Alto, California, 94305, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

University of Virginia School of Medicine

Charlottesville, Virginia, 22903, United States

RECRUITING

Related Publications (3)

• Chen SG, Tsai CH, Lin CJ, Lee CC, Yu HY, Hsieh TH, Liu HL. Transcranial focused ultrasound pulsation suppresses pentylenetetrazol induced epilepsy in vivo. Brain Stimul. 2020 Jan-Feb;13(1):35-46. doi: 10.1016/j.brs.2019.09.011. Epub 2019 Sep 24.

  PMID: 31575487 BACKGROUND

• Chu PC, Yu HY, Lee CC, Fisher R, Liu HL. Pulsed-Focused Ultrasound Provides Long-Term Suppression of Epileptiform Bursts in the Kainic Acid-Induced Epilepsy Rat Model. Neurotherapeutics. 2022 Jul;19(4):1368-1380. doi: 10.1007/s13311-022-01250-7. Epub 2022 May 17.

  PMID: 35581489 BACKGROUND

• Lee CC, Chou CC, Hsiao FJ, Chen YH, Lin CF, Chen CJ, Peng SJ, Liu HL, Yu HY. Pilot study of focused ultrasound for drug-resistant epilepsy. Epilepsia. 2022 Jan;63(1):162-175. doi: 10.1111/epi.17105. Epub 2021 Nov 2.

  PMID: 34729772 BACKGROUND

MeSH Terms

Conditions

Drug Resistant Epilepsy; Epilepsy; Seizures

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Sheang-Tze Fung, Ph.D.

CONTACT

02-25860560; stfung@navifus.com

Arthur Lung, Ph.D.

CONTACT

arthur.lung@navifus.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2024
• First Posted: April 29, 2024
• Study Start: September 13, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): May 31, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)