Acute Modulation of Stereotyped High-Frequency Oscillations

Epilepsy Clinical Trial

Official title:

Acute Modulation of Stereotyped High-Frequency Oscillations With a Closed-Loop Brain Interchange System in Drug-Resistant Epilepsy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05439655
• Other study ID #: 23-008859
• Secondary ID: 1UH3NS117944-01A
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2021
• Est. completion date: August 31, 2026

Study information

• Verified date: January 2024
• Source: Mayo Clinic
• Contact: Nuri F Ince, PhD
• Phone: 7137434461
• Email: nfince[@]uh.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Overall, this study will investigate the functional utility of stereotyped HFOs by capturing them with a new implantable system (Brain Interchange - BIC of CorTec), which can sample neural data at higher rates >=1kHz and deliver targeted electrical stimulation to achieve seizure control. In contrast to current closed-loop systems (RNS), which wait for the seizure to start before delivering stimulation, the BIC system will monitor the spatial topography and rate of stereotyped HFOs and deliver targeted stimulation to these HFO generating areas to prevent seizures from occurring. If the outcomes of our research in an acute setting become successful, the investigators will execute a clinical trial and run the developed methods with the implantable BIC system in a chronic ambulatory setting.

Description:

High-frequency oscillations (HFOs) of intracranial EEG (iEEG) have the potential to identify the surgical resection area/seizure onset zone (SOZ) in patients with drug-resistant epilepsy. However, multiple reports indicate that HFOs can be generated not only by epileptic cerebral tissue but also by non-epileptic sites often including eloquent regions such as motor, visual, and language cortices. In this project, the initial evidence of a recurrent waveform pattern is presented that may be sufficient to distinguish pathological HFOs from physiological ones. Specifically, the investigators show that the SOZ repeatedly generates sets of stereotypical HFOs with similar waveform morphology whereas the events recorded from out of SOZ were irregular. This morphological pattern served as a robust neurobiomarker to isolate SOZ from other brain areas in multiple patients consistently. While these promising preliminary results are in place, the functional utility of stereotyped HFOs in a closed-loop seizure control system remains unknown. As of today, not much is known whether the stereotyped HFOs generated by the SOZ can be detected with an implantable system. If this can be achieved, then HFOs can be strategically translated as a neurobiomarker into closed-loop seizure control applications. The investigators hypothesize that pathologic stereotyped HFOs can be captured with the implantable Brain Interchange (BIC) system of CorTec and spatial topography of these events can be utilized by the implantable system to deliver targeted electrical stimulation to achieve seizure control. Using an acute setup within the epilepsy monitoring unit (EMU), this project will investigate the feasibility of capturing stereotyped HFO events using the new BIC system and compare the detection results to those obtained with the commercially available amplifier (Aim-1). If the first phase (Aim-1) of the study becomes successful, later in the second phase (Aim-2), once again in the EMU, the investigators will deliver targeted electrical stimulation to those brain sites associated with stereotyped HFOs using the BIC.

During the entire study, the BIC system will not be implanted but used externally to assess the neural data through externalized electrodes and then deliver closed-loop stimulation. If the outcomes of the research in an acute setting become successful, the investigators will execute a clinical trial and run our methods with the implanted BIC system in a chronic ambulatory setting.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 31, 2026
• Est. primary completion date: July 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 70 Years

Eligibility

Inclusion Criteria:

• patients with medically refractory epilepsy, who have been deemed appropriate candidates for intracranial EEG monitoring

• Adult men and women (18= age <70 years)

• children (3= age <18 years)

• includes women and minorities

Exclusion Criteria:

• Subjects will be excluded if their condition makes them unable to continue with recordings.

Related Conditions & MeSH terms

• Epilepsy

Intervention

Device:
• Brain Interchange System
The CorTec Brain Interchange (BIC) is an implantable system with sensing and stimulation capability dedicated to promoting brain computer interface and closed-loop neuromodulation research. It is an externally powered implant which can provide neural data to a nearby computing station (communication unit connected to a personal computer) continuously. In return, computing station controls the implant e.g. for generating therapeutic electrical stimulation to the brain. It is expected that BIC will catalyze translational applications of electroceuticals in human subject by making the neural data immediately available as well as permit the investigation of novel closed-loop neuromodulation applications.

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas
United States	University of Houston	Houston	Texas

Sponsors (4)

Lead Sponsor	Collaborator
Mayo Clinic	Baylor College of Medicine, CorTec GmbH, National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Robustness in Data Transmission	Outcome-1 will quantify the feasibility of robust data recording and transmission with the BIC system in the epilepsy monitoring unit (EMU). The investigators will develop software tools to communicate with the BIC directly from MATLAB and Simulink. The incoming data from the implantable system will be visualized with gHIsys, the high-speed data processing libraries of gTec. At the end of the first year, in the epilepsy monitoring unit (EMU), the investigators will test the feasibility of recoding iEEG data from 2 patients continuously over 24 hours with less than <5% data loss. The BIC system will not be implanted but used externally to record the neural data. The research team will also test to record iEEG/ECoG data simultaneously with 2 BIC units to be ready for those cases where the number of recording channels are larger than =>32 and <=64. At this stage Outcome-1 is only related to the device feasibility (robust data transmission) not health related outcome.	Over 24 hours within the first year of project
Primary	Feasibility of Detection of Stereotyped HFOs	Outcome-2 will test the feasibility of capturing stereotyped HFO (sHFO) with the BIC system in the EMU setting. Once the feasibility of robust data transmission as listed in (Outcome-1) is tested, the neural activity will be recorded over 24 hours using the BIC system from 10 patients. The hardware will not be implanted but used externally to record the neural data. Then, the research team will compare whether the sHFO detection and SOZ localization accuracy is significantly different between the BIC and FDA approved amplifier. If the investigators can detect stereotyped HFOs with a rate not less than 75% of FDA approved clinical amplifier and predict the SOZ in 8/10 patients, then the research team will move to the second phase of the project to test Outcome-3. Outcome-2 tests the feasibility of capturing relevant neural events with the external BIC system and compares the recording quality to the FDA approved amplifiers. Outcome-2 does not test any health-related outcome.	Within the first 3 years of the project
Primary	Feasibility of Delivering Closed-Loop Stimulation	Outcome-3 will test the feasibility of delivering of closed-loop stimulation with the BIC system. If the detection of sHFO with the BIC system is feasible (Outcome-2), the investigators will start to test the online methods on the previously recorded datasets to isolate sHFOs in streaming iEEG/ECoG. Using the computer in the loop real-time system and the BIC, in the last 2 years, closed-loop stimulation will be delivered. In total 8 patients will be recruited for this particular purpose. Targeted stimulation will be delivered to those channels associated with sHFOs and other areas which are not associated with sHFOs. The research team will test if the device can deliver stimulation to selected channels without any failure. The BIC system will not be implanted but used externally to deliver the stimulation. Outcome-3 does not test whether the system can control the seizures of the patients. It only investigates the feasibility of delivering closed-loop stimulation.	In the 4th and 5th years of the project