Clinical trial NCT06898138: Acute Stimulation and Modulation of Stereotyped High-Frequency Oscillations
Official title: Acute Stimulation for the Modulation of Epileptic Events with a Closed-Loop Brain Interchange System in Drug Resistant Epilepsy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Epilepsy
Keywords: neuromodulation
HFO
Epilepsy
Machine Learning
Closed-Loop
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Baylor College of Medicine
name: CorTec GmbH
First posted: 2025-03-27
Enrollment: 8
Sex: ALL
Minimum age (years): 3
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: In a multi-phase structure, the project will investigate the feasibility of recording the HFOs with the BIC system (Cortec, Germany) and then delivering closed-loop stimulation.

In this phase of the project, the feasibility of delivering of closed-loop stimulation with the implantable system will be tested. For this 8 subjects will be recruited.

Therefore, in this phase of the study, a total 8 subjects will be recruited in a sequential fashion to test device feasibility.
Primary purpose: DEVICE_FEASIBILITY

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Feasibility of Detection of Stereotyped HFOs
timeFrame: Within the first 3 years of the project
measure: Feasibility of Delivering Closed-Loop Stimulation
timeFrame: In the 4th and 5th years of the project
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
References:
citation: Ayyoubi AH, Fazli Besheli B, Quach MM, Gavvala JR, Goldman AM, Swamy CP, Bartoli E, Curry DJ, Sheth SA, Francis DJ, Ince NF. Benchmarking signal quality and spatiotemporal distribution of interictal spikes in prolonged human iEEG recordings using CorTec wireless brain interchange. Sci Rep. 2024 Feb 8;14(1):2652. doi: 10.1038/s41598-024-52487-5.