Biomarker Targeted Stimulation for Epileptiform Events (BTSEE)

Safety and Effectiveness of Biomarker Targeted Stimulation in Epilepsy

This is a multicenter, prospective, controlled study designed to evaluate treatment with the BTS System.

Study Overview

• Status: Not yet recruiting
• Conditions: Epilepsy
• Intervention / Treatment: Device: Biomarker Targeted Stimulation (BTS)

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: David Himes, BSEE; Phone Number: 425-679-9505; Email: dhimes@cadenceneuro.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject is greater than or equal to 7 years of age.
2. Subject has focal onset seizures.
3. Subject has failed treatment with a minimum of two AED's used in typical therapeutic dosages.
4. Subject has seizures that are distinct, stereotypical events that can be reliably counted by the patient or caregiver.
5. Subject can reasonably be expected to maintain a seizure diary and the BTS System alone, or with the assistance of a competent individual.
6. For one month prior to enrollment, subject's anti-epileptic medication dosages and ketogenic diet (as applicable) have been stable (other than acute, intermittent use of benzodiazepines) and subject has had at least three primary, disabling seizures per month, on average. Seizures must be separated by a minimum of eight hours not to be considered part of a cluster. A cluster, for the purpose of this criterion, shall be considered a single seizure.
7. Subject is able to complete regular office visits and telephone appointments in accordance with the study protocol requirements.
8. A female subject of childbearing age must have a negative serum pregnancy test within two weeks prior to implant of the INSR, and, if sexually active, must be using a reliable form of birth control, be surgically sterile, or be at least two years post-menopausal.
9. Subject has been informed of their eligibility for resective surgery as a potential alternative to the study, if such surgery is a reasonable option.
10. Subject has had a brain MRI epilepsy evaluation within the past two years.
11. Subject's anatomy will permit implantation of the INSR within 20 mm of the skin surface.

Exclusion Criteria:

1. Subject has a history of substance abuse within the preceding two years.
2. Subject participated in another drug or device trial that may confound study results within the preceding 30 days.
3. Subject is implanted with pacemaker, implantable cardiac defibrillator, cardiac management product, or a medical device that interferes with the BTS System or with which the BTS System interferes. Patients with a vagus nerve stimulator (VNS) implanted may be enrolled, provided their clinical status has been stable for at least one month prior to enrollment at their current stimulation parameter settings.
4. Subject has anatomy that may interfere with electrode placement.
5. Subject is on anticoagulants and is unable to discontinue them perisurgically, as required by the neurosurgeon or Investigator.
6. Subject has significant platelet dysfunction from medical conditions or medications (including, particularly, aspirin or sodium valproate). If platelet dysfunction is suspected, subject can be enrolled only if a hematologist, the Investigator, and the neurosurgeon judge it to be advisable.
7. Subject has been diagnosed with psychogenic or non-epileptic seizures that cannot be distinguished from their epileptogenic events.
8. Subject is ineligible for cranial surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment

Device: Biomarker Targeted Stimulation (BTS); Using continuous stimulation to target multiple network nodes, Biomarker Targeted Stimulation (BTS) is intended to suppress abnormal interictal activity, as determined by biomarkers including interictal epileptiform discharges (IED) and high frequency oscillations (HFO), with the intention to reduce brain hyperexcitability, thereby limiting seizure occurrence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse event rate	Determine adverse event rate, including adverse device effects and serious adverse events	Intervals through 7, 12, and 24 months post-implant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seizure frequency	Using seizure diaries, calculate disabling seizure frequency, normalized to months, compared to baseline.	Intervals calculated at 4 to 7 months and through 12 and 24 months post-implant.
Neurocognitive testing	Neurocognitive tests, using the NIH Toolbox, including the Flanker Inhibitory Control and Attention Test, Picture Sequence Memory Test, and Picture Vocabulary Test, compared to baseline.	Evaluated at 7 months, 12 months, and 24 months post-implant.
Depression testing	Patient reported depression evaluation using Child Depression Inventory (CDI) or Beck Depression Inventory (BDI) (depending on age), compared to baseline.	Evaluated at 7 months, 12 months, and 24 months post-implant.
Anxiety testing	Patient reported anxiety evaluation using Revised Children's Manifest Anxiety Scale (RCMAS-2) or Beck Anxiety Inventory (depending on age), compared to baseline.	Evaluated at 7 months, 12 months, and 24 months post-implant.
Quality of life testing	Patient reported quality of life evaluation using Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55), Quality of Life in Epilepsy Inventory for Adolescents (QOLIE-AD-48), or Quality of Life in Epilepsy (QOLIE-31) (depending on age), compared to baseline.	Evaluated at 7 months, 12 months, and 24 months post-implant.
Sleep testing	Patient reported sleep evaluation using Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) or Epworth Sleepiness Scale (ESS) (depending on age), compared to baseline.	Evaluated at 7 months, 12 months, and 24 months post-implant.
Seizure severity testing	Patient reported seizure severity evaluation using Liverpool Seizure Severity Scale 2.0 (LSSS 2.0), compared to baseline.	Evaluated at 7 months, 12 months, and 24 months post-implant.
Caregiver burden testing	Caregiver reported burden evaluation using Caregiver Burden Inventory (CBI), compared to baseline.	Evaluated at 7 months, 12 months, and 24 months post-implant.

Collaborators and Investigators

• Sponsor: Cadence Neuroscience

Publications and helpful links

General Publications

• Lundstrom BN, Worrell GA, Stead M, Van Gompel JJ. Chronic subthreshold cortical stimulation: a therapeutic and potentially restorative therapy for focal epilepsy. Expert Rev Neurother. 2017 Jul;17(7):661-666. doi: 10.1080/14737175.2017.1331129. Epub 2017 May 25.
• Kerezoudis P, Grewal SS, Stead M, Lundstrom BN, Britton JW, Shin C, Cascino GD, Brinkmann BH, Worrell GA, Van Gompel JJ. Chronic subthreshold cortical stimulation for adult drug-resistant focal epilepsy: safety, feasibility, and technique. J Neurosurg. 2018 Aug;129(2):533-543. doi: 10.3171/2017.5.JNS163134. Epub 2017 Oct 20.
• Lundstrom BN, Gompel JV, Khadjevand F, Worrell G, Stead M. Chronic subthreshold cortical stimulation and stimulation-related EEG biomarkers for focal epilepsy. Brain Commun. 2019;1(1):fcz010. doi: 10.1093/braincomms/fcz010. Epub 2019 Sep 6.
• Starnes K, Miller K, Wong-Kisiel L, Lundstrom BN. A Review of Neurostimulation for Epilepsy in Pediatrics. Brain Sci. 2019 Oct 18;9(10):283. doi: 10.3390/brainsci9100283.
• Alcala-Zermeno JL, Gregg NM, Van Gompel JJ, Stead M, Worrell GA, Lundstrom BN. Cortical and thalamic electrode implant followed by temporary continuous subthreshold stimulation yields long-term seizure freedom: A case report. Epilepsy Behav Rep. 2020 Sep 2;14:100390. doi: 10.1016/j.ebr.2020.100390. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): February 14, 2030

Study Registration Dates

• First Submitted: May 9, 2024
• First Submitted That Met QC Criteria: May 17, 2024
• First Posted (Actual): May 22, 2024

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: CAD2004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No