Clinical trial NCT03417297: A Pilot Study: Focused Ultrasound Thalamotomy for the Prevention of Secondary Generalization in Focal Onset Epilepsy
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Partial Seizures With Secondary Generalization
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Focused Ultrasound Foundation
First posted: 2018-01-31
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a pilot study. There are no statistical testing. Ten (10) adults with refractory, partial-onset epilepsy with secondary generalization and able to provide informed consent will be enrolled. 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), an additional 7 participants will be enrolled.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and feasibility of Magnetic Resonance Imaging-guided focused ultrasound (MRgFUS) in patients with 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 the seizures. Safety will be measured by recording and analyzing any adverse effects that may occur from the day of the experimental surgery through 12 months following the surgery.

Detailed description: This is a open-label prospective intervention study. Ten (10) adults with refractory, partial-onset epilepsy with secondary generalization and able to provide informed consent will be enrolled. 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), an additional 7 participants 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 absence 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 diary. Quality of life will be measured by the Quality of Life in Epilepsy Inventory (QOLIE-31). Imaging analysis will include study of 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.

Eligibility criteria: Inclusion Criteria:

* Disabling, medically refractory epilepsy (≥2 anti-epileptic drug failures)
* Focal onset seizures with secondary generalization; with or without primary generalized seizures.
* ≥ 3 seizures/month on average within 3 months of enrollment.
* Stable medication dosage 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).
* Involved care provider.
* Written informed consent to participate.
* Previous seizure work-up within 12 months of enrollment date to include:

  1. Home EEG or 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:

* Low seizure frequency (\<3 seizures/month).
* Indwelling vagal nerve stimulator.
* Severe untreated neuropsychiatric disorders (untreated depression or behavioral problems).
* Recent history of drugs or alcohol abuse.
* Primary generalized epilepsy (Lennox Gastaut, drop attacks).
* Post infectious epilepsy (i.e., post-herpetic).
* Previous corpus callosotomy.
* Significant structural brain abnormalities.
* Unable or unwilling to maintain drug dosage for 3 months post treatment.
* Pregnant or not practicing birth control method acceptable to the principal investigator.
* History of claustrophobia.
* Known allergic reaction and/or hypersensitivity to IV dye and/or IV contrasting agent(s).
* MRI contraindicated implanted metal or medical device.
* Uncontrolled hypertension or other comorbid conditions
* 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.

Primary outcomes:
measure: Number of Participants with Successful Lesion Creation
timeFrame: during the surgical procedure
measure: Number of Participants with Adverse Events
timeFrame: 12 months
Secondary outcomes:
measure: Change in Number of Seizures Reported Across Time
timeFrame: up to 12 months
measure: Total QOLIE-31-P Score Across Time
timeFrame: up to 12 months
measure: Change MRI parameter (Water Diffusivity)
timeFrame: Baseline, (Day 1), Month 3
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina-Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Vibhor Krishna, MD SM
role: PRINCIPAL_INVESTIGATOR
References: