Assessment of MRI-guided HIFU for Patients With Drug-resistant Focal Epilepsy (EPIFUS)

Clinical and Radiological Assessment of MRI-guided High-intensity Focused Ultrasound for Patients With Drug-resistant Focal Epilepsy

The goal of this clinical trial is to assess the feasibility, safety, and tolerance of MRI-guided High-Intensity Focused Ultrasound (HIFU) for the treatment of drug-resistant focal epilepsy in adult patients with MRI-visible brain lesions.

The main question it aims to answer is whether HIFU can safely and effectively achieve the target ablative temperature (≥52 °C) within epileptogenic lesions, thereby enabling successful thermal ablation of the epileptogenic focus.

This pilot, single-center study is single arm, prospective, non-comparative and uncontrolled. This will take place over a period of 24 months. After information (V1), inclusion (V2) and presurgical (V3) visits, a surgical visit will be performed during hospitalization in the neurosurgery department (V4) for HIFU therapy and 5 follow-up consultation visits (V5, V6, V7, V8, and V9 to J7, M1, M3, M6, and M12).

Study Overview

• Status: Not yet recruiting
• Conditions: Epilepsy
• Intervention / Treatment: Procedure: MR-guided HIFU thermoablation; Diagnostic test: EEG; Diagnostic test: MRI

Detailed Description

Epilepsy is a common, long-lasting neurological disorder with significant social ramifications. In France, it is estimated that over 500,000 individuals are affected by epilepsy, with 50,000 experiencing drug-resistant partial epilepsy. Approximately 10,000 patients with drug-resistant partial epilepsy may benefit from neurosurgical treatment to excise their epileptogenic focus. However, only 300 operations are performed annually in France. Epilepsy surgery not only has medical benefits (with 50-80% of operated patients being seizure-free), but also reduces the risk of excess mortality in this population. Furthermore, it is a cost-effective solution, as drug-resistant epileptic patients can cost up to $138,000 in treatment and monitoring throughout their lifetime. High-Intensity Focused Ultrasound (HIFU) is a noninvasive method that uses heat to destroy brain lesions, leading to coagulation and necrosis of the lesion under control. It has been successfully used to treat essential tremors, Parkinson's disease, and neuropathic pain, and may be used to treat epilepsy lesions that are inaccessible to conventional surgery, located in eloquent areas, or in patients with contraindications to general anesthesia. The goal of this study is to assess the feasibility, tolerance, and safety of HIFU use in lesions responsible for drug-resistant epilepsy, as this represents the first use of HIFU for this indication.

Main objective : To assess the feasibility of employing HIFU-based thermoablation for the treatment of drug-resistant epilepsy caused by intracerebral lesions.

• Study Type: Interventional
• Enrollment (Estimated): 13
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bertrand Mathon, MD PhD; Phone Number: + 33 1 42 16 34 08; Email: bertrand.mathon@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years old
2. Patient with drug-resistant epilepsy according to ILAE definition
3. Patient presenting lesional image(s) on morphological MRI responsible for epilepsy according to clinical and electrophysiological evaluation, +/-PET+/- SPECT+/-sEEG
4. Patients for whom neurosurgical treatment by craniotomy is not possible: deep-seated lesions, lesions in the eloquent area, patient reluctance to have a surgical procedure with craniotomy, contraindication to general anesthesia
5. Patient affiliated to a social security scheme
6. The patients signed an informed consent form.

Exclusion Criteria:

1. Drug-sensitive epilepsy
2. Patients exhibiting suboptimal adherence to medication
3. Individuals under legal protective measures
4. Patients presenting contraindications to Magnetic Resonance Imaging (MRI), such as the presence of metal fragments, allergy to gadolinium, etc.
5. Patients with serious and uncontrolled psychiatric disorders
6. Pregnant women. Women of reproductive capacity were mandated to use oral contraceptives throughout the study duration.

7. Contraindications related to ExAblate treatment:

   • patients with implants in the brain or skull.
   • patients where it is not possible to avoid energy-absorbing structures or sensitive tissues (e.g., skull density ratio <0.35, areas of anterior brain shunts, surgical clamps, or other hard implants) on the path of the ultrasound beam.
   • patients diagnosed with another brain disease (e.g., malignant brain tumors or intracranial aneurysms).
   • patients with a history of cerebral hemorrhage, and stroke within the last year.
   • patients taking medications that are predisposed to bleeding and have not stopped for two weeks before the procedure.
   • patients with severe hypertension that cannot be controlled with medication (diastolic blood pressure >100 mmHg).
   • patients who could not communicate with the physician during the treatment.
   • patients with unstable cardiac conditions.
   • patients with history of abnormal bleeding, intracranial hemorrhage, coagulopathy, or documented risk factors for intraoperative or postoperative bleeding or coagulopathy.
   • patients with cerebrovascular disease (multiple strokes or strokes within six months).
   • patients with risk factors for intraoperative or postoperative bleeding.
   • patients with significant healing in an area located on the path of the intended passage of energy to the treatment area.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Assigned Interventions

Procedure: MR-guided HIFU thermoablation; - HIFU-based thermoablation: non-invasive brain tissue ablation by a MRI-guided transcranial ultrasound (MRgFUS) system. • Installation of a stereotaxy frame: 4 cranial skin points under local anesthesia with Xylocaine, Perfalgan IV 2g in IVL, usual brushing protocol with iodized alcohol, and removal of stereotaxy frame • MRI with contrast agent administration acquisition and definition of the area to be treated and ultrasound parameters by neurosurgeons, neuroradiologists, and physicists. • Realization of thermoablation under real-time control using MRI and clinical control.; Diagnostic test: EEG; Surface EEG: assessment of residual seizures and interictal epileptiform activity.; Diagnostic test: MRI; Brain MRI in the Neuroradiology department to monitor lesion volume, possible reactive edema, and possible mass effect. The imaging protocol will include 3D T1, 3D T2, 3D FLAIR, SWI, Diffusion and 3D T1 after gadolinium injection sequences.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target ablative temperature	Achievement of the target ablative temperature (at least one timepoint at 52 °C (15 °C above body temperature)) on calorimetric MRI sequences performed in real time during HIFU treatment (real-time quantitative measurements + CSV data extracted at the end of the procedure).	During the procedure between 60 and 75 days after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-intervention complications of grade≥2	Clinical safety: Post-intervention complications at D30 of grade≥2 (complications requiring therapeutic intervention or after-effects or death) according to Mathon et al., Journal of Neurology, 2015.	From day 0 to day 30 after the procedure.
Morphological MRI	Evaluation measured by morphological MRI corresponding to necrosis induced by MRI (axes, volume, ablation margins).	From the day of the procedure up to 12 months after the procedure.
Thermometric MRI monitoring during HIFU thermoablation		At D0 during the procedure
Cumulative thermal dose during HIFU thermoablation		At D0 during the procedure
ILAE classification		At 12 months after the procedure
Frequency of epileptic seizures	Number of epileptic seizures using the seizure diary starting	From inclusion up to 12 months after the procedure
Intensity of epileptic seizures	Intensity of epileptic seizures using the seizure diary	From inclusion up to 12 months after the procedure
Change in antiepileptic treatment	Number of antiepileptic drugs, modification in antiepileptic dose.	From inclusion up to 12 months after the procedure
Antiepileptic effectiveness EEG	Surface EEG in comparison with pretreatment EEG (seizures, interictal abnormalities).	From inclusion up to 12 months after the procedure
Neuropsychological evaluation	Change from pre-treatment assessment performed in the inclusion work-up of the neuropsychological assessment at M12	At inclusion and at 12 months
Evaluation of quality of life	Mean change of global score of quality of life according to the quality of life in epilepsy inventory-31 (QOLIE-31) questionnaire from pre-treatment assessment during the inclusion work-up at M12.	At inclusion and at 12 months
MRI-assessed radiological safety	Thermometric MRI monitoring on D0, induced edema on D7 and D30	From the day of the procedure up to days 30 after the procedure
Adverse events related to HIFU treatment	Frequency, intensity, and severity of adverse effects collected during treatment and follow-up period	From the D0 the day of procedure up to 12 months after the procedure

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: April 16, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Epilepsy; Epilepsy surgery; HIFU; drug-resistant epilepsy; thermoablation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Drug Resistant Epilepsy; Epilepsy; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Electrodiagnosis; Electroencephalography
• Other Study ID Numbers: APHP240803

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No