Optimizing Therapy in Epilepsy Using Seizure Forecasts Via EEG and Wearables

NCT07012148 | Recruiting Early Phase 1 DMC FDA Drug FDA Device

• 2 other identifiers: 23-005125UG3NS123066-02
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

Mayo Clinic is conducting a research study to test a new approach to managing seizures in people with epilepsy whose seizures have not been fully controlled with regular medications. The study uses a small sensor placed just under the skin (not inside the brain) that continuously records electrical brain activity. This information is used to train a personalized computer algorithm that learns your individual seizure patterns and forecasts when a seizure is more likely to occur. If you are eligible and choose to participate, you would receive advance warning of elevated seizure risk, allowing you to take a fast-acting medication before a seizure happens. This medication would be in addition to the regular medicines prescribed by your doctor. The goal of the study is to understand whether this kind of forecasting system is safe, comfortable to live with, and capable of helping people gain more control over their seizures with a minimum amount of additional medication. Participation involves a minor surgical procedure to implant a small electrode under the skin above your ear that records your brain's electrical signals continuously over time. You would also wear a smart watch during the study. For the first six months, the system collects data to personalize your seizure forecast model and would not give you an alert. In the second six months, we would calculate your daily seizure risk and you would receive alerts on days when your risk is elevated. On these higher seizure risk days you would take a prescribed fast-acting nasal spray medication. The study is open to adults who continue to have 2 or more seizures per month in spite of having tried at least two antiseizure medications in the past, and whose seizures have shown involvement of the temporal lobe. All study-related procedures, devices, and study medication are provided at no cost to participants. Participants receive financial compensation for their time, and travel expenses to and from Mayo Clinic Rochester are reimbursed for anyone traveling more than 100 miles. If you are interested in learning more, please contact our research coordinator by email at Laivell.Jeffrey@mayo.edu.

Conditions

Focal Epilepsy; Generalized Seizure; Drug Refractory Epilepsy

Keywords

complex partial seizure; UNEEG; seizure forecasting; Subscalp EEG; Benzodiazepine

Outcome Measures

Primary Outcomes (4)

• Safety and Adverse Events

  VALTOCO discontinuation rate due to TEAE below 10% of subjects

  12 months

• Safety- cardiorespiratory events

  no observed drug-related serious cardiorespiratory events

  12 months

• Feasibility outcome

  greater than 75% data collection adherence (18 hours/day) with the UNEEG and Apple Watch systems on average during the prospective forecasting portion of the study for over 90% of participants

  12 months

• Preseizure alert feasibility

  greater than 80% of pre-seizure alerts resulting in VALTOCO administration within 90 minutes in over 90% of participants

  12 months

Secondary Outcomes (3)

• Reduction in seizure rates during the prospective phase of the trial compared to baseline

  12 months

• Quality of Life Inventory and seizure related impact scores

  Baseline, 6 months, 12 months

• Seizure related severity score

  Baseline, 6months, 12months

Study Arms (1)

subscalp EEG

EXPERIMENTAL

All study subjects will be implanted with the UNEEG SubQ device and will receive forecasts of daily seizure risk.

Device: UNEEG SubQ device, seizure forecasts, nasal diazepam; Drug: Preventative Medication (PM)

Interventions

Preventative Medication (PM) DRUG

Subjects will take nasal diazepam in response to pre-seizure alerts to evaluate the potential for this medication to prevent seizures.

subscalp EEG

UNEEG SubQ device, seizure forecasts, nasal diazepam DEVICE

Subjects will be implanted with the UNEEG SubQ device in the neurosurgical operating suite. Electrodes will be placed over the temporal lobe of the hemisphere established as the origin of seizures by previous EEG monitoring. Only one UNEEG device will be placed, and only the seizure onset hemisphere will be covered. Subjects will have individualized seizure forecast models created, and will take a supplemental antiseizure medicine during periods of elevated seizure risk.

subscalp EEG

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects enrolled in this study must have epilepsy involving the temporal lobe and will have undergone video-EEG monitoring within the past 3 years, and will have met the following criteria:
• Focal epilepsy, including complex partial, and secondarily generalized seizures, including:
• disabling seizure (i.e. involving loss of awareness, motor control, speech, or other essential functions) counts at least 2 per month on average over the preceding 3 months, established by verbal history or caregiver report.
• For 3 months prior to enrollment, subject's AED dosages have been stable (less than a 25% change in dosage) and subject has had at least two seizures per month, on average, with a seizure-free interval not to exceed 60 days. Seizures must be separated by a minimum of four hours not to be considered part of a cluster. A cluster, for the purpose of this criterion, shall be considered a single seizure.
• With the exception of epilepsy, subject must be medically and neurologically stable.
• Age 18 to 75.
• Ability and willingness to provide informed consent and participate in the study protocol. Subject is able to interpret and to respond, in accordance with the study protocol, to the advisory indicators provided by the device.
• Subject has seizures that are distinct, stereotypical events that can be reliably counted by the subject or caregiver, and have a distinct EEG pattern that can be recorded using subscalp EEG over the frontotemporal head region, established by video-EEG monitoring.
• Subject can reasonably be expected to maintain a seizure diary alone or with the assistance of a competent individual.
• Subject is able to complete regular office visits and telephone appointments in accordance with the study protocol requirements.
• Subject's seizure focus, based upon clinical semiology, scalp EEG, intracranial electroencephalographic (iEEG) findings, and/or neuroimaging, demonstrate consistent involvement of the temporal lobe with their EEG seizure pattern.
• Subject speaks and reads English.
• Subject has no reason to anticipate requiring a magnetic resonance imaging (MRI) evaluation within the next two years.
• Subject has EEG documentation of ictal events consistent with his or her predominant current seizure type.
• Subject's anatomy will permit implantation of the UNEEG SubQ device in the opinion of the study's neurosurgeon.

You may not qualify if:

• For 3 months prior to enrollment, subject's AED dosages have not been stable (greater than 25% change in dosage), or subject has had more than 30 disabling seizures per month, on average, or more than 10 seizure days per month, on average.
• Subject needs to have magnetic resonance imaging during the study period.
• Subject has a substance abuse history (alcohol, prescription, or illicit medications) within the preceding two years.
• Subject participated in another drug or device trial within the preceding 30 days.
• Subject has been hospitalized for a psychiatric condition within the preceding two years or has had a history of psychosis within the preceding two years (excluding post-ictal psychosis).
• Subject is implanted with pacemaker, implantable cardiac defibrillator, cardiac management product, brain stimulator, or other medical device that would interfere with the UNEEG device. This includes, but is not limited to, direct brain neurostimulators, spinal cord stimulators, and cochlear implants. Vagus nerve stimulators are not expected to interfere with the subscalp EEG device and will be permitted, as long as stimulation parameters can be reasonably expected to remain stable (25% or less change in amplitude) throughout the study.
• Subject has experienced unprovoked status epilepticus.
• Subject has had therapeutic surgery to treat epilepsy that may interfere with electrode placement in the judgement of the neurosurgeon.
• Subject is on anticoagulants and is unable to discontinue them perisurgically, as required by the neurosurgeon or Investigator.
• 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. Blood tests to evaluate platelet and bleeding disorder issues will be obtained prior to enrollment.
• Subject is otherwise ineligible for cranial surgery, or the Investigators identify other medical or psychosocial factors that would counter indicate participation in the study.
• Subject has a known diagnosis of psychogenic nonepileptic seizures (PNES)
• Female subject is pregnant or plans to become pregnant.
• Subject is known to require rescue medication for seizure clusters
• Subject has a history of a paradoxical reaction to benzodiazepines including agitation, hyperactivity, or aggression.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (3)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

RECRUITING

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Publications (4)

• Cloyd J, Haut S, Carrazana E, Rabinowicz AL. Overcoming the challenges of developing an intranasal diazepam rescue therapy for the treatment of seizure clusters. Epilepsia. 2021 Apr;62(4):846-856. doi: 10.1111/epi.16847. Epub 2021 Feb 22.

  PMID: 33617690 BACKGROUND

• Pal Attia T, Viana PF, Nasseri M, Duun-Henriksen J, Biondi A, Winston JS, P Martins I, Nurse ES, Dumpelmann M, Worrell GA, Schulze-Bonhage A, Freestone DR, Kjaer TW, Brinkmann BH, Richardson MP. Seizure forecasting using minimally invasive, ultra-long-term subcutaneous EEG: Generalizable cross-patient models. Epilepsia. 2023 Dec;64 Suppl 4(Suppl 4):S114-S123. doi: 10.1111/epi.17265. Epub 2022 May 4.

  PMID: 35441703 BACKGROUND

• Viana PF, Pal Attia T, Nasseri M, Duun-Henriksen J, Biondi A, Winston JS, Pavao Martins I, Nurse ES, Dumpelmann M, Schulze-Bonhage A, Freestone DR, Kjaer TW, Richardson MP, Brinkmann BH. Seizure forecasting using minimally invasive, ultra-long-term subcutaneous electroencephalography: Individualized intrapatient models. Epilepsia. 2023 Dec;64 Suppl 4(Suppl 4):S124-S133. doi: 10.1111/epi.17252. Epub 2022 Apr 16.

  PMID: 35395101 BACKGROUND

• Nasseri M, Stirling RE, Viana PF, Cui J, Nurse E, Karoly PJ, Kremen V, Dumpelmann M, Worrell GA, Freestone DR, Richardson MP, Brinkmann BH. Forecasting epileptic seizures with wearable devices: A hybrid short- and long-horizon pseudo-prospective approach. Epilepsia. 2025 Sep;66(9):3293-3308. doi: 10.1111/epi.18466. Epub 2025 May 24.

  PMID: 40411751 BACKGROUND

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Epilepsies, Partial; Seizures; Drug Resistant Epilepsy

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Benjamin Brinkmann, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Gregory A Worrell, MD, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Jamie J Van Gompel, MD

  Mayo Clinic

  STUDY DIRECTOR

Central Study Contacts

Jeff Laivell

CONTACT

507-538-8095; laivell.jeffrey@mayo.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DEVICE FEASIBILITY
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: All study participants will be implanted with a subscalp EEG system. Personalized seizure forecasting algorithms will be developed, and this will be used to prompt subjects to take a supplemental antiseizure medicine.

Study Record Dates

• First Submitted: May 21, 2025
• First Posted: June 10, 2025
• Study Start: January 20, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: September 25, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)