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

Official title

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

Overview

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).

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.

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. • Re
• 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.

Primary outcome measures

• Target ablative temperature [Time frame: During the procedure between 60 and 75 days after inclusion]

Secondary outcome measures (12)

• Post-intervention complications of grade≥2 [Time frame: From day 0 to day 30 after the procedure.]
• Morphological MRI [Time frame: From the day of the procedure up to 12 months after the procedure.]
• Thermometric MRI monitoring during HIFU thermoablation [Time frame: At D0 during the procedure]
• Cumulative thermal dose during HIFU thermoablation [Time frame: At D0 during the procedure]
• ILAE classification [Time frame: At 12 months after the procedure]
• Frequency of epileptic seizures [Time frame: From inclusion up to 12 months after the procedure]
• Intensity of epileptic seizures [Time frame: From inclusion up to 12 months after the procedure]
• Change in antiepileptic treatment [Time frame: From inclusion up to 12 months after the procedure]
• Antiepileptic effectiveness EEG [Time frame: From inclusion up to 12 months after the procedure]
• Neuropsychological evaluation [Time frame: At inclusion and at 12 months]
• Evaluation of quality of life [Time frame: At inclusion and at 12 months]
• MRI-assessed radiological safety [Time frame: From the day of the procedure up to days 30 after the procedure]

Eligibility criteria

Inclusion criteria

• Age ≥18 years old
• Patient with drug-resistant epilepsy according to ILAE definition
• Patient presenting lesional image(s) on morphological MRI responsible for epilepsy according to clinical and electrophysiological evaluation, +/-PET+/- SPECT+/-sEEG
• 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
• Patient affiliated to a social security scheme
• The patients signed an informed consent form.

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07591350 · APHP240803

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗