Not yet recruitingNCT07927985ClinicalTrials.gov record

RESTORE: Restoring State-dependent Thalamocortical Oscillations in Epilepsy

Epilepsy, Drug Resistant

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THE QUICK READ

What this study involves

The registry does not currently label this study as recruiting. Ask about its status before planning a screening visit.

Study type: Interventional
Phase: Not applicable
Age range: 18 years - Not specified
Sex eligible: All sexes
Healthy volunteers: Not accepted
Participants: 10 Estimated

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

The purpose of this research study is to determine the safety and effectiveness of the investigational Cadence Biomarker Targeted Stimulation (BTS) System (Model 5100 EEG Workstation and Alera Model 2000 Biomarker Stimulation System), when used to reduce the frequency of seizures in patients with generalized onset epilepsy.

Read the full description

This prospective, randomized, sham-controlled study will evaluate the safety, feasibility, and clinical effectiveness of the investigational Cadence Biomarker Targeted Stimulation (BTS) System in adults with drug-resistant generalized epilepsy. The study will enroll 10 adult participants (≥18 years of age) across participating Mayo Clinic sites.

The Cadence BTS System is designed to provide deep brain stimulation (DBS) and record brain electrical activity. The system includes the Model 5100 EEG Workstation and the Alera implantable neural stimulation and recording system. Participants will undergo implantation of four DBS leads targeting the bilateral centromedian (CM) and mediodorsal (MD) nuclei of the thalamus. During implantation, intra-operative neurophysiologic recordings and brief stimulation trials will be used to evaluate brain responses, identify electrophysiologic biomarkers, and help select stimulation contacts and parameters for chronic therapy.

The study will include a baseline/enrollment phase, an implant phase, a CM-DBS optimization phase, a randomized CM+MD DBS evaluation phase, and an open-label phase. During the baseline phase, participants will record seizure frequency and undergo baseline clinical, neurological, neuropsychological, mood, memory, sleep, and quality-of-life assessments. Following implantation, CM stimulation will be optimized using clinical response, seizure counts, electrophysiologic biomarkers, and participant tolerability.

During the randomized evaluation phase, participants will continue optimized CM stimulation while receiving randomized MD stimulation conditions, including sham stimulation, low-frequency stimulation, and high-frequency stimulation. Participants will continue to record seizure frequency, and clinical and neuropsychological assessments will be performed following the randomized treatment periods. Participants will subsequently enter an open-label phase using the therapy determined to be optimal based on findings from the randomized phase.

The primary objective is to evaluate the safety and feasibility of combined bilateral CM and MD thalamic stimulation delivered using the Cadence BTS System. Safety will be assessed through monitoring of device-related, procedure-related, and stimulation-related adverse events and serious adverse events, as well as neurological examinations, neuropsychological testing, mood and behavioral assessments, and device performance.

Clinical effectiveness will be evaluated primarily by comparing disabling seizure frequency during treatment with each participant's baseline seizure frequency. Additional outcomes will include seizure responder rate (≥50% reduction in disabling seizure frequency), seizure freedom, total seizure frequency, seizure severity, quality of life, cognition, memory, mood, sleep, functional outcomes, electrophysiologic biomarkers, and long-term device performance.

Exploratory analyses will examine relationships between suppression of electrophysiologic biomarkers and seizure reduction, associations among sleep, cognition, mood, and seizure outcomes, stimulation parameters associated with clinical response, and longitudinal changes in thalamocortical network activity. These findings are intended to provide preliminary information to support future studies of biomarker-guided and adaptive thalamic neuromodulation for generalized epilepsy.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

Inclusion Criteria:

Generalized-onset seizures.
Failure of at least two appropriately selected and adequately dosed anti-seizure medications.
Distinct, stereotyped seizures that the participant or caregiver can reliably count.
Ability, independently or with a competent assistant, to maintain a seizure diary and use the BTS System.
Stable anti-seizure medication doses and ketogenic diet, if applicable, for 1 month before enrollment, except acute intermittent benzodiazepine use.
At least 3 disabling seizures per month on average. Seizures separated by less than 8 hours are counted as one cluster for this criterion.
Ability to complete required office and telephone or video visits.
For participants of childbearing potential: negative serum pregnancy test within 2 weeks before implantation and use of reliable contraception, surgical sterility, or at least 2 years postmenopausal.
Informed of reasonable alternatives, including surgery, other devices, medication, and dietary options.
Adequate epilepsy-protocol brain MRI within the previous 2 years.
Anatomy permits implantation of the INSR within 20 mm of the skin surface.

Exclusion Criteria:

Substance abuse within the previous 2 years.
Participation within the previous 30 days in another drug or device study that may confound results.
Implanted pacemaker, implantable cardioverter-defibrillator, cardiac management product, vagus nerve stimulator, or other medical device that interferes with the BTS System or is affected by it.
Anatomy that the surgical team determines may preclude safe electrode implantation.
Use of anticoagulants that cannot be discontinued perioperatively as required.
Significant platelet dysfunction due to a medical condition or medication unless a hematologist, investigator, and neurosurgeon agree enrollment is advisable.
Psychogenic or nonepileptic seizures that cannot be distinguished from epileptic events.
Ineligibility for cranial surgery or a medically or neurologically unstable condition, including brain tumor, multiple sclerosis, dementia, or intracranial vascular lesion.
Active psychosis, major depression, or suicidal ideation within the previous 6 months.
Unprovoked convulsive status epilepticus within the previous year, defined as a tonic-clonic seizure lasting at least 5 minutes or repeated tonic-clonic seizures without recovery of consciousness for more than 5 minutes.
Participant or legally authorized representative cannot demonstrate ability to provide valid informed consent in accordance with regulatory requirements.
In the investigator's opinion, the individual is a poor candidate for the study.

Understand screening

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment: Random assignment
Masking: Quadruple masked

Sham, High Frequency, Low Frequency

All participants receive four deep brain stimulation leads implanted bilaterally in the centromedian (CM) and mediodorsal (MD) thalamic nuclei.

After CM stimulation is optimized, participants complete three blinded, randomized 3-month periods of MD stimulation-sham, low frequency, and high frequency-in a participant-specific sequence while optimized CM stimulation continues.

Participants then enter an open-label phase and receive the stimulation settings selected as optimal based on the randomized periods.

Device: Sham Mediodorsal Thalamic (MD) Deep Brain Stimulation + Centromedian Thalamic (CM) Deep Brain Stimulation · Device: Low-Frequency Mediodorsal Thalamic Deep Brain Stimulation · Device: High-Frequency Mediodorsal Thalamic Deep Brain Stimulation · Device: Mediodorsal Thalamic Deep Brain Stimulation using optimal settings

Sham, Low Frequency, High Frequency

All participants receive four deep brain stimulation leads implanted bilaterally in the centromedian (CM) and mediodorsal (MD) thalamic nuclei.

Participants then enter an open-label phase and receive the stimulation settings selected as optimal based on the randomized periods.

Low Frequency, Sham, High Frequency

All participants receive four deep brain stimulation leads implanted bilaterally in the centromedian (CM) and mediodorsal (MD) thalamic nuclei.

Participants then enter an open-label phase and receive the stimulation settings selected as optimal based on the randomized periods.

Low Frequency, High Frequency, Sham

All participants receive four deep brain stimulation leads implanted bilaterally in the centromedian (CM) and mediodorsal (MD) thalamic nuclei.

Participants then enter an open-label phase and receive the stimulation settings selected as optimal based on the randomized periods.

High Frequency, Sham, Low Frequency

All participants receive four deep brain stimulation leads implanted bilaterally in the centromedian (CM) and mediodorsal (MD) thalamic nuclei.

Participants then enter an open-label phase and receive the stimulation settings selected as optimal based on the randomized periods.

High Frequency, Low Frequency, Sham

All participants receive four deep brain stimulation leads implanted bilaterally in the centromedian (CM) and mediodorsal (MD) thalamic nuclei.

Participants then enter an open-label phase and receive the stimulation settings selected as optimal based on the randomized periods.

Sham Mediodorsal Thalamic (MD) Deep Brain Stimulation + Centromedian Thalamic (CM) Deep Brain Stimulation DEVICE

The implanted Cadence BTS System is programmed so that no therapeutic MD stimulation is delivered during the 3-month sham period. Optimized centromedian nucleus thalamus (CM) stimulation continues. This intervention is administered once to every participant in the period specified by the assigned sequence.

Low-Frequency Mediodorsal Thalamic Deep Brain Stimulation DEVICE

The implanted Cadence BTS System delivers protocol-defined low-frequency stimulation to the bilateral MD thalamic nuclei for 3 months while optimized CM stimulation continues. This intervention is administered once to every participant in the period specified by the assigned sequence.

High-Frequency Mediodorsal Thalamic Deep Brain Stimulation DEVICE

The implanted Cadence BTS System delivers protocol-defined high-frequency stimulation to the bilateral MD thalamic nuclei for 3 months while optimized CM stimulation continues. This intervention is administered once to every participant in the period specified by the assigned sequence.

Mediodorsal Thalamic Deep Brain Stimulation using optimal settings DEVICE

After the randomized periods, all participants enter an open-label phase and receive the stimulation settings selected as optimal.

Prepare your questions

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

Number of Participants With a Device, Procedure, or Stimulation-Related Serious Adverse Events

Time frame: From device implantation through Month 21

Number of participants who experience at least one serious adverse event assessed by the investigator as related to the Cadence Biomarker Targeted Stimulation System, the device-implantation procedure, or delivered deep brain stimulation.