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

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ClinicalTrials.gov Identifier: NCT03417297
Recruitment Status : Recruiting
First Posted : January 31, 2018
Last Update Posted : April 26, 2018
Sponsor:
Collaborator:
Focused Ultrasound Foundation
Information provided by (Responsible Party):
Vibhor Krishna, Ohio State University

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 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.

Condition or disease Intervention/treatment Phase
Partial Seizures With Secondary Generalization Device: high intensity focused ultrasound Not Applicable

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 Ohio State University 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 this 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 -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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Primary Purpose: Device Feasibility
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
Actual Study Start Date : April 24, 2018
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : February 28, 2021

Resource links provided by the National Library of Medicine


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 MR guides 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 up to an additional 7 participants will be enrolled.
Device: high intensity focused ultrasound
high intensity focused ultrasound
Other Name: ExAblate Model 4000 Type-1 focused ultrasound




Primary Outcome Measures :
  1. Feasibility [ Time Frame: during the surgical procedure ]
    development of altered mental status (not explained by the administration of routine anesthetic or pain medications) or severe neurological deficits (e.g. weakness/numbness/tingling in arms or legs, or aphasia)

  2. Safety [ Time Frame: 12 months ]
    Neuropsychological determination of cause for suspension/termination will 2 include detection of statistically and clinically meaningful decline among 2 of the initial 3 subjects enrolled; else among 4 of the total 10 subjects expected to be enrolled. This is determined through reliable change index analysis comparing raw subject performance scores in language, memory, and executive function domains with existing data published in test manuals to determine whether 3-month performance represents a clinically and statistically meaningful decline in at least two measures in one of these domains. We intend to use the McSweeny et al. RCI model.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • 18-65 years of age, inclusive.
  • Previous seizure work-up within 12 months of enrollment date to include:

    • Home EEG or EMU video EEG or intracranial EEG.
    • Baseline neuropsychological assessment, which includes the Wechsler Advanced Clinical Solutions - Test of Premorbid Functioning (TOPF). Subjects obtaining an IQ score of ≥70 on the TOPF will be included.
    • High definition MRI imaging/PET imaging.

Exclusion Criteria:

  • Low seizure frequency (<3 seizures/month).
  • Previous vagal nerve stimulator.
  • Severe untreated neuropsychiatric disorders (untreated depression or behavioral problems).
  • Recent history of drugs or alcohol abuse.
  • Generalized epilepsy (Lennox Gastaut, drop attacks).
  • Post infectious epilepsy (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).
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03417297


Contacts
Contact: Angela S Emerson, MPH 614.685.3141 angela.emerson@osumc.edu
Contact: Carson R Reider, PhD 614.293.9274 carson.reider@osumc.edu

Locations
United States, Ohio
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Angela S Emerson, MPH    614-685-3141    angela.emerson@osumc.edu   
Sponsors and Collaborators
Vibhor Krishna
Focused Ultrasound Foundation
Investigators
Principal Investigator: Vibhor Krishna, MD SM Ohio State University

Responsible Party: Vibhor Krishna, Assistant Clinical Professor, Ohio State University
ClinicalTrials.gov Identifier: NCT03417297     History of Changes
Other Study ID Numbers: 2017H0446
First Posted: January 31, 2018    Key Record Dates
Last Update Posted: April 26, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
Neoplasm Metastasis
Epilepsy
Seizures
Neoplastic Processes
Neoplasms
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms