A Pilot Study to Evaluate the Efficacy and Safety of NaviFUS™ System Neuromodulating Treatment for Patients With Drug Resistant Epilepsy

This will be a prospective, pilot, open-label, two-arm, parallel-group, randomized study to evaluate the efficacy and safety of low-intensity focused ultrasound (LIFU) neuromodulation using NaviFUS System in patients with drug-resistant epilepsy (DRE).

The study aims to demonstrate the efficacy and safety of LIFU neuromodulation in DRE patients, showing its ability to decrease targeted neuronal activity and alleviate epileptic seizures.

Drug-resistant epilepsy (at least 3 anti-seizure medication failed) patients whose epileptogenic foci have been determined by comprehensive presurgical evaluation and meet all eligibility criteria may participate in this study by providing informed consent. Eligible patients will undergo a 8-week 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 16 eligible patients. Eligible patients will be randomized into two groups to receive three-consecutive 5-minute twice (low dose group) or three-consecutive 10-minute FUS treatment twice (high dose group) in a week using assigned ultrasound exposure doses generated by the NaviFUS System. Following treatment, there will be a 24-week follow-up period. Patients will be allowed concomitant use of anti-seizure medications (ASMs) throughout the whole study period.

Eligibility Criteria:
Inclusion Criteria:

1. Male or female patients aged over than and equal to 18 years old.
2. Patients with drug-resistant epilepsy (defined as at least 3 ASM failed) and 1-4 ASM at the time of study entry.
3. Epileptogenic focus (or foci) is determined by comprehensive presurgical evaluation.
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. Willing and able to sign written informed consent and be able to comply with the study protocol during the study period.

Exclusion Criteria:

1. Patients with concurrent active psychiatric or mood disorders that have been assessed to interfere with participation in the study.
2. Presence of pacemaker, implantable cardioverter-defibrillator (ICD), permanent medication pumps, cochlear implants, or deep brain stimulation (DBS).
3. The skull bone area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), wounds, or atrophy of the scalp.
4. Image documented calcified lesion in the FUS exposure path.
5. Abnormal coagulation profile:

   1. Platelet (PLT) \< 100,000/μL.
   2. prothrombin time (PT) \> 15 sec.
   3. activated partial thromboplastin time (APTT) \> 45 sec.
   4. international normalized ratio (INR) \> 1.5.
   5. Patients requiring anticoagulant medications.
6. Pregnant or breast-feeding women.
7. Coexisting medical problems of sufficient severity to limit compliance with the study.
8. Known sensitivity/allergy to Magnetic Resonance Imaging (MRI) contrast agents or any of its components; having metallic implants that are assessed as unsuitable for MRI examination.
9. Use of any recreational drugs or history of drug addiction or known history of substance or alcohol abuse.
10. Patients have received an investigational drug or an investigational device within 4 weeks prior to the study
11. 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.
12. Any ASM treatment change during the baseline (screening period).
13. Vagus nerve stimulation (VNS) dosing changes within 2 months before baseline (screening period).
14. Radiofrequency thermocoagulation (RFTC) within 2 months before baseline (screening period).
15. Patient has an IQ \< 70, based on the Wechsler Abbreviated Scale of Intelligence (WASI-III or IV).
16. Any other condition that, in the investigator's judgment, patient not applicable to participate this study.