Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03417297
Recruitment Status : Recruiting
First Posted : January 31, 2018
Last Update Posted : September 23, 2019
Sponsor:
Collaborator:
Focused Ultrasound Foundation
Information provided by (Responsible Party):
Vibhor Krishna, Ohio State University

Tracking Information
First Submitted Date  ICMJE January 10, 2018
First Posted Date  ICMJE January 31, 2018
Last Update Posted Date September 23, 2019
Actual Study Start Date  ICMJE April 24, 2018
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2018)
  • 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)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 24, 2018)
  • Number of participants with treatment-related adverse events [ Time Frame: Up to 15 months per study subject ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
  • Feasibility [ Time Frame: During surgical procedure ]
    ability to create the desired lesion within the anterior nucleus
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2018)
  • Seizure frequency [ Time Frame: Incidence of seizures recorded up to 15 months per study subject ]
    Seizure frequency data will be collected by seizure diary
  • Resting state functional connectivity [ Time Frame: To be measured on the day of surgery at times immediately preceding and post the surgical procedure ]
    Changes in resting state functional connectivity will be assessed by functional MRI
  • Quality of Life [ Time Frame: To be measured within 30 days of the surgery and then again at approximately 7, 30, 90 180 and 365 days after the surgery ]
    Quality of life will be measured by Quality of Life in Epilepsy Inventory -31.
  • Structural brain anatomy changes [ Time Frame: To be measured on the day of surgery at times immediately preceding and post the surgical procedure ]
    Structural brain anatomy measurements will be conducted suing volumetric T1 and T2 weighted imaging.
  • Microstructural brain anatomy changes [ Time Frame: To be measured on the day of surgery at times immediately preceding and post the surgical procedure ]
    Microstructural brain changes will be assessed by diffusion tensor
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Pilot Study: Focused Ultrasound Thalamotomy for the Prevention of Secondary Generalization in Focal Onset Epilepsy
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
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
Condition  ICMJE Partial Seizures With Secondary Generalization
Intervention  ICMJE Device: high intensity focused ultrasound
high intensity focused ultrasound
Other Name: ExAblate Model 4000 Type-1 focused ultrasound
Study Arms  ICMJE 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.
Intervention: Device: high intensity focused ultrasound
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 24, 2018)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2021
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Erin Woodburn 614.366.7822 erin.woodburn@osumc.edu
Contact: Carson R Reider, PhD 614.293.9274 carson.reider@osumc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03417297
Other Study ID Numbers  ICMJE 2017H0446
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Vibhor Krishna, Ohio State University
Study Sponsor  ICMJE Vibhor Krishna
Collaborators  ICMJE Focused Ultrasound Foundation
Investigators  ICMJE
Principal Investigator: Vibhor Krishna, MD SM Ohio State University
PRS Account Ohio State University
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP