Drug Resistant EpilepsyPhase 1/2NCT06388707
A Safety, Tolerability, and Preliminary Efficacy of Low-intensity Focused Ultrasound Neuromodulation in Patients With Drug-resistant Epilepsy
A Phase 1/2 study testing NaviFUS System in people with Drug Resistant Epilepsy and Epilepsy, run by NaviFUS Corporation at 3 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Drug Resistant Epilepsy, Epilepsy, Seizures, Focal
- What is being tested?
- NaviFUS System
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 3 sitesUnited States
- Study dates
- 13 Sep 2024to 31 Oct 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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 comply with study procedures, with or without hair shaving 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.
Who cannot join
- 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.
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- 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.
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Arthur Lung, Ph.D. contact
United States3 sites, 3 recruiting
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Ellen Bubrick, M.D.
- Recruiting
University of Virginia School of Medicine
Charlottesville, Virginia, 22903
Nathan Fountain, M.D.
- Recruiting
Stanford University School of Medicine
Palo Alto, California, 94305
Robert Fisher, M.D., Ph.D.
About this study
Official title: 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 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).
Read the detailed description
The study aims to demonstrate the safety and preliminary efficacy of LIFU neuromodulation in DR-TLE patients, showing its ability to decrease targeted neuronal activity and alleviate epileptic seizures.
Patients diagnosed with epilepsy who meet all eligibility criteria may participate in this study by providing informed consent, either in person or through their legal representative. Eligible patients will undergo a 2-month baseline observation screening period and will be asked to keep a 8-week seizure diary. This diary will serve as a baseline prior to treatment and will continue to be recorded throughout the treatment and follow-up period.
This study will enroll a maximum of 8 eligible patients through competitive enrollment. Patients will receive a total of 6 FUS treatments over 3 consecutive weeks using assigned ultrasound exposure doses generated by the NaviFUS System. Following treatment, there will be a 12-week follow-up period. Patients will be allowed concomitant use of anti-seizure medications (ASMs) throughout the whole study period.
- Conditions
- Drug Resistant Epilepsy, Epilepsy, Seizures, Focal, Seizure, Seizure Disorder
- Being tested
- NaviFUS System
- Keywords
- NaviFUS System, Focused Ultrasound, Low-Intensity Focused Ultrasound, LIFU
- Medical subject headings
- Drug Resistant Epilepsy, Epilepsy, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaviFUS SystemDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| FUS treatment | Experimental | Not described Receives: Device: NaviFUS System |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events (AEs)
The incidence and severity of AEs associated with LIFU neuromodulation in patients with drug-resistant unilateral or bilateral temporal lobe epilepsy.
Measured: up to 23 weeks
Secondary outcomes (6)
Change from baseline in seizure frequency
The changes in patient's seizure frequency during and after treatment will be assessed based on the seizure diaries.
Measured: up to 23 weeks
Change from baseline in electroencephalography (EEG) epileptiform discharges
The change in patient's epileptiform discharges after treatment will be assessed based on the EEG recording.
Measured: up to 15 weeks
Days of seizure-free
The changes in number of seizure-free days after FUS treatment(s).
Measured: up to 23 weeks
Changes from baseline in Beck Anxiety Inventory (BAI)
BAI is a 21-question multiple-choice self-report inventory that is used to measure the severity of anxiety. Each answer is scored on a scale value of 0 (not at all) to 3 (severely). Higher total scores indicate more severe anxiety symptoms.
Measured: up to 23 weeks
Changes from baseline in Beck Depression Inventory (BDI-II)
BDI-II, a 21-question multiple-choice self-report inventory, is a psychological test used to measure the severity of depression. Each answer is rated on a scale of 0 (none at all) to 3 (severe). Higher total scores indicate more severe depressive symptoms.
Measured: up to 23 weeks
Changes from baseline in Personal Impact of Epilepsy Scale (PIES)
PIES is a 25-item multiple-choice self-report inventory that is used to evaluate the overall impact of seizures, side effects, comorbidities, and overall quality of life for people with epilepsy. Each answer is rated by patient on a scale value of 0 (best) to 4 (worst). Lower total PIES scores reflect better overall status.
Measured: up to 23 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2024
- Study start13 Sep 2024
- Primary completion30 Jun 2027 (estimated)
- Study completion31 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Drug Resistant EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NaviFUS Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- NaviFUS US LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06388707
- Sponsor's protocol ID
- NF-2022-01
- Status last verified
- Sep 2026
- First submitted
- 24 Apr 2024
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 31575487Chu 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.
PubMed 35581489Lee 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.
PubMed 34729772
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06388707
- Acronym / sponsor ID
- NF-2022-01
- Conditions
- Drug Resistant Epilepsy, Epilepsy, Seizures, Focal, Seizure, Seizure Disorder
- Keywords
- NaviFUS System, Focused Ultrasound, Low-Intensity Focused Ultrasound, LIFU
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 8 participants (estimated)
- Lead sponsor
- NaviFUS CorporationIndustry (pharma, biotech, devices)
- Collaborators
- NaviFUS US LLC
- Study start
- 13 Sep 2024 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 31 Oct 2027 (estimated)
- First posted
- 29 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The study aims to demonstrate the safety and preliminary efficacy of LIFU neuromodulation in DR-TLE patients, showing its ability to decrease targeted neuronal activity and alleviate epileptic seizures.
Patients diagnosed with epilepsy who meet all eligibility criteria may participate in this study by providing informed consent, either in person or through their legal representative. Eligible patients will undergo a 2-month baseline observation screening period and will be asked to keep a 8-week seizure diary. This diary will serve as a baseline prior to treatment and will continue to be recorded throughout the treatment and follow-up period.
This study will enroll a maximum of 8 eligible patients through competitive enrollment. Patients will receive a total of 6 FUS treatments over 3 consecutive weeks using assigned ultrasound exposure doses generated by the NaviFUS System. Following treatment, there will be a 12-week follow-up period. Patients will be allowed concomitant use of anti-seizure medications (ASMs) throughout the whole study period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FUS treatment | Experimental | Device: NaviFUS System |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (16 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NaviFUS SystemFUS 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. | Device | FUS treatment |
Primary outcome
Adverse events (AEs)
Time frame: up to 23 weeks
The incidence and severity of AEs associated with LIFU neuromodulation in patients with drug-resistant unilateral or bilateral temporal lobe epilepsy.
6 secondary outcomes
Change from baseline in seizure frequency
Time frame: up to 23 weeks
Change from baseline in electroencephalography (EEG) epileptiform discharges
Time frame: up to 15 weeks
Days of seizure-free
Time frame: up to 23 weeks
Changes from baseline in Beck Anxiety Inventory (BAI)
Time frame: up to 23 weeks
Changes from baseline in Beck Depression Inventory (BDI-II)
Time frame: up to 23 weeks
Changes from baseline in Personal Impact of Epilepsy Scale (PIES)
Time frame: up to 23 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Background: PubMed 31575487Chen 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.
- Background: PubMed 35581489Chu 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.
- Background: PubMed 34729772Lee 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Arthur Lung, Ph.D. contact
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NaviFUS System in people with Drug Resistant Epilepsy and Epilepsy, run by NaviFUS Corporation at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sheang-Tze Fung, Ph.D. (02-25860560 ext. 167, stfung@navifus.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (AEs) (time frame: up to 23 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06388707, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.