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

NCT03417297 | Active Not Recruiting DMC FDA Device

• 1 other identifier: 22-0350
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Partial Seizures With Secondary Generalization; Focal Epilepsy With Secondary Generalization

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Change in Number of Seizures Reported Across Time

  up to 24 months

• Total QOLIE-31-P Score Across Time

  up to 12 months

• Change MRI parameter (water diffusivity)

  Baseline, (Day 1), Month 3

Study Arms (1)

high intensity focused ultrasound

EXPERIMENTAL

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

Interventions

High Intensity Focused Ultrasound DEVICE

Participants will undergo high intensity focused ultrasound surgery utilizing magnetic resonance (MR) imaging guidance using a 3 Tesla scanner.

Also known as: ExAblate Model 4000 Type-1 Focused Ultrasound

high intensity focused ultrasound

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Home EEG, Epilepsy Monitoring Unit (EMU) video EEG, or intracranial EEG.
• 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.
• High-definition MRI imaging/Position emission tomography (PET) imaging.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Focused Ultrasound Foundation: collaborator

Study Sites (1)

University of North Carolina-Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• Krishna V, Mindel J, Sammartino F, Block C, Dwivedi AK, Van Gompel JJ, Fountain N, Fisher R. A phase 1 open-label trial evaluating focused ultrasound unilateral anterior thalamotomy for focal onset epilepsy. Epilepsia. 2023 Apr;64(4):831-842. doi: 10.1111/epi.17535. Epub 2023 Mar 1.

  PMID: 36745000 DERIVED

Study Officials

• Vibhor Krishna, MD, SM

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a pilot study. Ten (10) adults with refractory, focal epilepsy with secondary generalization and able to provide informed consent will undergo focused ultrasound (FUS) thalamotomy. 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.

Study Record Dates

• First Submitted: January 10, 2018
• First Posted: January 31, 2018
• Study Start: April 24, 2018
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: August 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)