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

Thalamic Stimulation for Epilepsy Study

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04102254
Recruitment Status : Suspended (Lead acquisition from company & COVID-19 restrictions)
First Posted : September 25, 2019
Last Update Posted : May 13, 2020
Sponsor:
Information provided by (Responsible Party):
Duke University

Brief Summary:
In this study, the investigator aims to perform cortical stereo electroencephalogram (sEEG) recordings during simultaneous anterior nucleus of the thalamus (ANT) recording and stimulation to better understand the following: 1) how the ANT is involved in various seizure types; 2) which cortical regions are modulated by established ANT stimulation patterns; and 3) how novel ANT stimulation patterns modify epileptogenic cortical activity. Together, this knowledge will advance ANT deep brain stimulation (DBS) therapy by providing a physiologic basis for patient selection for ANT DBS, while identifying brain signals and stimulation patterns that can be used to develop novel methods for ANT DBS. Up to 15 adult patients (18 and older) who present to Duke Neurosurgery for routine seizure localization using sEEG will be asked to enroll in this pilot study of ANT recording and stimulation. In the course of surgical epilepsy treatment, patients routinely undergo surgical placement of sEEG electrodes for the purposes of seizure localization. During this procedure, 2 additional leads will be placed in the ANT. These patients remain hospitalized for 7-14 days after sEEG placement, during which time their seizure medications are tapered. Concurrent video monitoring is performed while continuous neural recordings are made through the sEEG electrodes. Additionally, continuous recordings will be performed through the electrodes placed in the thalamus. Periodically, standard intermittent high-frequency stimulation (130 Hz, 90-ms pulse width, and 2 mA intensity) will be performed with a 60-s on and a 300-s off cycle after surgery. These standard ANT stimulation parameters are employed clinically. Data will include the sEEG recordings marked for ANT stimulation, any side effects, medications, past medical history (PMH), and tests/procedures during the hospital stay. Risks involved are as described for the standard depth electrode surgery with the addition of the possible side effects from the stimulation which include sensations of numbness and tingling, and possibly increased seizure activity.

Condition or disease Intervention/treatment Phase
Seizures Epilepsy Seizure Disorder Procedure: ANT recording and stimulation Not Applicable

Detailed Description:

The purpose of this research is to examine the physiologic underpinnings of deep brain stimulation of the anterior nucleus of the thalamus (ANT), a method reducing seizures in adults diagnosed with medically refractory epilepsy. In this study, the investigator aims to perform cortical stereo electroencephalogram (sEEG) recordings during simultaneous ANT recording and stimulation to better understand the following: 1) how the ANT is involved in various seizure types; 2) which cortical regions are modulated by established ANT stimulation patterns; and 3) how novel ANT stimulation patterns modify epileptogenic cortical activity. Together, this knowledge will advance ANT DBS therapy by providing a physiologic basis for patient selection for ANT DBS, while identifying brain signals and stimulation patterns that can be used to develop novel methods for ANT DBS.

Approximately 3 million people in the United States experience epilepsy. Despite medical therapy, up to 30% of these patients continue to experience recurrent seizures. In this medically refractory population, tissue resection or ablation offer a high likelihood of seizure freedom, if a single epileptogenic focus can be precisely identified. For patients who are not candidates for resection or ablation, or those who continue to have seizures after these treatments, neuromodulation represents an alternative therapeutic option. One such therapy, deep brain stimulation (DBS) has been approved for around 5 years in Europe and was recently approved in the United States as a treatment for medically refractory epilepsy.

A number of potential DBS targets are being investigated, particularly, the ANT, which consists of the anteroventral, anterodorsal, and anteromedial nuclei. The ANT was recognized as a potential target because of its central connectivity to cortical regions where seizures often originate. Several pilot studies and recent trials have demonstrated 5-year efficacy and safety outcomes for ANT DBS. In a large randomized controlled study of ANT stimulation with long-term follow-up, there was a 56% median seizure reduction at the 2 year, and a 69% median and seizure reduction at the 5 year, in patients with drug-resistant focal epilepsy. This study also suggested that patients with temporal lobe epilepsy achieved greater benefit than those with extra-temporal or multifocal seizures. Since these pivotal trials, DBS of the ANT has emerged as a promising therapy for focal drug resistant epilepsy, however, its basic mechanism of action is unclear. One study which examined cortical local field potentials recordings during high-frequency ANT stimulation (130 Hz), has suggested that epileptic network desynchronization is a potential mechanism of DBS of the ANT.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Thalamic Stimulation for Epilepsy Study
Actual Study Start Date : November 7, 2019
Estimated Primary Completion Date : July 10, 2022
Estimated Study Completion Date : July 10, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy Seizures

Arm Intervention/treatment
Experimental: ANT recording and stimulation
Up to 15 adult patients who present to Duke Neurosurgery for routine seizure location using sEEG will be asked to enroll in this pilot study of ANT recording and stimulation. Once enrolled in the trial, subjects will have additional placement of two thalamic electrodes during the course of standard sEEG placement surgery. Patients routinely remain hospitalized for 7-14 days after sEEG placement, during which time their seizure medications are tapered. Continuous neural recordings are made through the sEEG electrodes for the purposes of seizure localization during the entire time the depth electrodes are in place. Up to three times daily, standard intermittent high-frequency stimulation [130 Hertz (Hz), 90-millisecond pulse width, and 2 milliamps (mA) intensity] will be performed with a 60-seconds on and a 300-seconds off cycle following surgery up to the entire length of sEEG monitoring.
Procedure: ANT recording and stimulation
In this study, the investigator aims to perform sEEG recordings during simultaneous ANT recording and stimulation to better understand the following: 1) how the ANT is involved in various seizure types; 2) which cortical regions are modulated by established ANT stimulation patterns; and 3) how novel ANT stimulation patterns modify epileptogenic cortical activity.




Primary Outcome Measures :
  1. Percent changes from baseline in power (dB) [ Time Frame: Measurements will be made 7-14 days following surgery for sEEG placement ]
    Differences of greater than 25% in magnitude in percent mean change in power between primary regions of interest will be reported. A maximum of 20 comparisons will be made.

  2. Percent changes from baseline in rates of interictal spikes [ Time Frame: Measurements will be made 7-14 days following surgery for sEEG placement ]
    Differences of greater than 25% in magnitude in percent mean change in rates of interictal spikes between primary regions of interest will be reported. A maximum of 20 comparisons will be made.

  3. Percent changes from baseline in rates of high frequency oscillations [ Time Frame: Measurements will be made 7-14 days following surgery for sEEG placement ]
    Differences of greater than 25% in magnitude in percent mean change in rates of high frequency oscillations between primary regions of interest will be reported. A maximum of 20 comparisons will be made.

  4. Percent changes in connectivity density [ Time Frame: Measurements will be made 7-14 days following surgery for sEEG placement ]
    Changes of greater than 25% in magnitude in connectivity density on versus off stimulation in primary regions of interest will be reported. A maximum of 20 comparisons will be made.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
All epilepsy patients admitted to Duke Hospital for surgical placement of depth electrodes age 18 and up are eligible.

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): NCT04102254


Locations
Layout table for location information
United States, North Carolina
Duke University Health System
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Investigators
Layout table for investigator information
Principal Investigator: Derek Southwell, M.D., Ph.D. Duke University Health System
Layout table for additonal information
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT04102254    
Other Study ID Numbers: Pro00103374
First Posted: September 25, 2019    Key Record Dates
Last Update Posted: May 13, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Study data will be stored in the Duke Research Electronic Data Capture (REDCap) database.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Epilepsy
Seizures
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms