## Protocol Section
### Identification Module
**NCT ID:** NCT06424977

**Acronym:** BTSEE

**Brief Title:** Biomarker Targeted Stimulation for Epileptiform Events

**Official Title:** Safety and Effectiveness of Biomarker Targeted Stimulation in Epilepsy

#### Organization Study ID Info
**ID:** CAD2004
#### Organization
**Class:** INDUSTRY
**Full Name:** Cadence Neuroscience
### Status Module
#### Completion Date
**Date:** 2028-09-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-22

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-17

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-12-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-09-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-22
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-09
**Study First Submit QC Date:** 2024-05-17
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Cadence Neuroscience

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** True

**Is FDA Regulated Drug:** False

**Is Unapproved Device:** True

**Oversight Has DMC:** True

### Description Module

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

### Conditions Module

**Conditions:**

- Epilepsy

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 40

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Device: Biomarker Targeted Stimulation (BTS)

**Label:** Treatment

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Treatment

**Description:** 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.

**Name:** Biomarker Targeted Stimulation (BTS)

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** Determine adverse event rate, including adverse device effects and serious adverse events

**Measure:** Adverse event rate

**Time Frame:** Intervals through 7, 12, and 24 months post-implant

#### Secondary Outcomes

**Description:** Using seizure diaries, calculate disabling seizure frequency, normalized to months, compared to baseline.

**Measure:** Seizure frequency

**Time Frame:** Intervals calculated at 4 to 7 months and through 12 and 24 months post-implant.

**Description:** 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.

**Measure:** Neurocognitive testing

**Time Frame:** Evaluated at 7 months, 12 months, and 24 months post-implant.

**Description:** Patient reported depression evaluation using Child Depression Inventory (CDI) or Beck Depression Inventory (BDI) (depending on age), compared to baseline.

**Measure:** Depression testing

**Time Frame:** Evaluated at 7 months, 12 months, and 24 months post-implant.

**Description:** Patient reported anxiety evaluation using Revised Children's Manifest Anxiety Scale (RCMAS-2) or Beck Anxiety Inventory (depending on age), compared to baseline.

**Measure:** Anxiety testing

**Time Frame:** Evaluated at 7 months, 12 months, and 24 months post-implant.

**Description:** 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.

**Measure:** Quality of life testing

**Time Frame:** Evaluated at 7 months, 12 months, and 24 months post-implant.

**Description:** 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.

**Measure:** Sleep testing

**Time Frame:** Evaluated at 7 months, 12 months, and 24 months post-implant.

**Description:** Patient reported seizure severity evaluation using Liverpool Seizure Severity Scale 2.0 (LSSS 2.0), compared to baseline.

**Measure:** Seizure severity testing

**Time Frame:** Evaluated at 7 months, 12 months, and 24 months post-implant.

**Description:** Caregiver reported burden evaluation using Caregiver Burden Inventory (CBI), compared to baseline.

**Measure:** Caregiver burden testing

**Time Frame:** Evaluated at 7 months, 12 months, and 24 months post-implant.

### Eligibility Module

**Eligibility Criteria:** 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.

**Minimum Age:** 7 Years

**Sex:** MALE

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** dhimes@cadenceneuro.com

**Name:** David Himes, BSEE

**Phone:** 425-679-9505

**Role:** CONTACT

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

### References Module

#### References

**Citation:** 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.

**PMID:** 28532252

**Citation:** 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.

**PMID:** 29053073

**Citation:** 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.

**PMID:** 31667473

**Citation:** 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.

**PMID:** 31635298

**Citation:** 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.

**PMID:** 32995742

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M7983

- Name: Epilepsy

- Relevance: HIGH

- As Found: Epilepsy

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000004827

- Term: Epilepsy

### Misc Info Module

- Version Holder: 2024-05-31
