A Pilot Study: Focused Ultrasound Thalamotomy for the Prevention of Secondary Generalization in Focal Onset Epilepsy

A Pilot Open-label Clinical Trial Evaluating the ExAblate Model 4000 Type-1 Focused Ultrasound Thalamotomy for the Prevention of Secondary Generalization in Focal Onset Epilepsy

The purpose of this study is to assess the safety and feasibility of unilateral focused ultrasound thalamotomy in adults with focal onset epilepsy whose medicines are not working well. The ExAblate (ExAblate) transcranial system is the name of the device that will be used to create and send ultrasound waves through the scalp and skull precisely to a small structure located in the center of the brain. This structure is known as the "Anterior Nucleus", and is an important region in the brain that may cause seizures. Safety will be measured by recording and analyzing the frequency of side effects throughout participation. Feasibility will be measured by the ability to create a lesion in the anterior nucleus.

Study Overview

• Status: Active, not recruiting
• Conditions: Partial Seizures With Secondary Generalization; Focal Epilepsy With Secondary Generalization
• Intervention / Treatment: Device: High Intensity Focused Ultrasound

Detailed Description

This is an open-label prospective intervention study. Ten (10) adults with refractory, focal epilepsy with secondary generalization and able to provide informed consent will undergo focused ultrasound (FUS) thalamotomy. In addition to the diagnosis of medically refractory epilepsy, these patients will need to meet protocol specific inclusion and exclusion criteria. These adults will be screened from the patients being cared for by the epilepsy program at the University of North Carolina at Chapel Hill or referred from elsewhere for enrollment in the study. Initially, 3 participants will be enrolled and followed for 3 months to assess the safety of study intervention. Pending review by the Data and Safety Monitoring Committee (DSMC) and the US Food and Drug Administration (FDA), additional subjects will be enrolled.

This pilot study is being conducted to test the feasibility of this device in order to confirm the design and operating specifications of the device including the ability to identify and accurately ablate the target focus within the Anterior Nucleus.

Safety will be assessed by the frequency of side effects, e.g., new onset of neurological deficits, performance deterioration on neuropsychological testing. Feasibility is defined as the ability to create the desired lesion within the anterior nucleus.

Seizure frequency data will be collected by seizure questionnaire. Quality of life will be measured by the Quality of Life in Epilepsy Inventory (QOLIE-31). Imaging analysis will include a comparison of pre- and post-intervention imaging to identify brain networks associated with clinical outcomes and determine changes in resting-state functional connectivity (assessed by fMRI), as well as in structural (assessed by volumetric T1 and T2 weighted imaging) and microstructural (assessed by diffusion tensor imaging) brain anatomy.

Subject satisfaction with FUS thalamotomy will be assessed by the Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19).

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina-Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Medically refractory epilepsy (≥2 antiepileptic drug failures) deemed disabling by the patient and study investigators.
• Focal seizures with secondary generalization; with or without primary generalized seizures.
• ≥ 3 seizures/month on average based on seizure diary of patient's preferred format during the three months prior to enrollment.
• Stable prescribed epilepsy medication dosages, including stopping or starting medication, for 3 months before enrollment.
• Anterior Nucleus (AN) identifiable on MRI (structural T1 and T2 images).
• Willing to maintain seizure diary (3 months before & 3 months after the study treatment).
• Involved caregiver such as a spouse, family member, or family friend willing to provide reliable care during the study participation.
• Ability to provide written informed consent to participate.

• Previous seizure work-up to include:

  1. Home EEG, Epilepsy Monitoring Unit (EMU) video EEG, or intracranial EEG.
  2. Baseline neuropsychological assessment, which includes the Wechsler Advanced Clinical Solutions - Test of Premorbid Functioning (TOPF). Participants obtaining an Intelligence Quotient (IQ) score of ≥70 on the TOPF will be included.
  3. High-definition MRI imaging/Position emission tomography (PET) imaging.

Exclusion Criteria:

• Have on average less than 3 seizures a month.
• Have an indwelling vagal nerve stimulator.
• Have severe untreated neuropsychiatric disorders (e.g., untreated depression or behavioral problems).
• History of drug or alcohol abuse in the last 12 months.
• Presence of primary generalized epilepsy (e.g., Lennox Gastaut, drop attacks).
• Presence of post-infectious epilepsy (i.e., epilepsy from post-herpetic encephalitis).
• Previous corpus callosotomy (surgery to cut the fibers, called the corpus callosum, that separate each half of the brain).
• Significant structural brain abnormalities.
• Unable or unwilling to maintain your current anti-seizure drug dosage for 3 months post-treatment.
• Pregnant or not practicing birth control methods.
• History of claustrophobia (fear of closed spaces).
• Presence of an MRI contraindicated implanted metal or medical device (e.g., pacemaker, metallic joints, or insulin pump).
• Uncontrolled hypertension or other comorbid conditions (e.g., uncontrolled heart or lung disease).
• Skull Density Ratio (SDR) <0.4.
• IQ score of <70 on the Wechsler Advanced Clinical Solutions - Test of Premorbid Functioning (TOPF), a measure conducted as part of baseline neuropsychological assessment.

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: high intensity focused ultrasound; Initially, 3 patients will be enrolled and followed for 3 months to assess the safety of study intervention which is unilateral focused ultrasound thalamotomy (anterior nucleus). These data will be reviewed by the Data and Safety Monitoring Committee (DSMC) and the FDA. If approval is granted by the DSMC and FDA, then additional subjects will be enrolled.

Device: High Intensity Focused Ultrasound; Participants will undergo high intensity focused ultrasound surgery utilizing magnetic resonance (MR) imaging guidance using a 3 Tesla scanner.; Other Names: ExAblate Model 4000 Type-1 Focused Ultrasound

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Successful Lesion Creation	Feasibility is defined as the ability to create the desired lesion within the anterior nucleus in 80% or more of participants.	during the surgical procedure
Number of Participants with Adverse Events	Safety will be assessed by the frequency of side effects, e.g. new onset of neurological deficits, performance deterioration on neuropsychological testing.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Number of Seizures Reported Across Time	Captured by participant-recorded seizure questionnaires. Assessed at Baseline, Day 7, Day 30, and months 3, 6, 12 and 24.	up to 24 months
Total QOLIE-31-P Score Across Time	The Quality of Life in Epilepsy Inventory-31-Problems (QOLIE-31-P) is a survey of health-related quality of life for adults with epilepsy. The QOLIE-31-P is completed by the patient. It contains 39 items, of which a total of 30 are used to make up 7 different subscales. Scores range from 0-100, with higher scores indicating a greater level of functioning and QoL. Assessed at Baseline, and months 1, 3, 6, and 12.	up to 12 months
Change MRI parameter (water diffusivity)	Water Diffusivity assessed by structural and microstructural MRI in a voxel-wise manner and compared between pre and post operative MRI.	Baseline, (Day 1), Month 3

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Focused Ultrasound Foundation
• Investigators: Principal Investigator: Vibhor Krishna, MD, SM, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2018
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: January 10, 2018
• First Submitted That Met QC Criteria: January 24, 2018
• First Posted (Actual): January 31, 2018

Study Record Updates

• Last Update Posted (Estimated): August 15, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Epilepsy; Seizures; Epilepsies, Partial
• Other Study ID Numbers: 22-0350

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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