An interventional study of Sham Mediodorsal Thalamic (MD) Deep Brain Stimulation + Centromedian Thalamic (CM) Deep Brain Stimulation and Low-Frequency Mediodorsal Thalamic Deep Brain Stimulation in Epilepsy, Drug Resistant, sponsored by Gregory Worrell. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-10.
Sponsored by Gregory Worrell · Not applicable, Interventional, and Device feasibility
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.
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.
257 studies on the registry are indexed under Drug Resistant Epilepsy; 108 are open to participants now.
This study's planned enrollment of 10 is below the median of 30 across 202 interventional studies indexed under Drug Resistant Epilepsy.
Browse Drug Resistant Epilepsy studies →This is the only study on the registry with Gregory Worrell as lead sponsor.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
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
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
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
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
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.
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.
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.
After the randomized periods, all participants enter an open-label phase and receive the stimulation settings selected as optimal.
Number of Participants With a Device, Procedure, or Stimulation-Related Serious Adverse Events
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.
Time frame: From device implantation through Month 21
Change in Monthly Disabling Seizure Frequency
Percent change in number of disabling seizures as reported in seizure diary. Disabling seizures include generalized tonic-clonic seizures, tonic seizures, atonic seizures, focal-to-bilateral tonic-clonic seizures, and other seizure types associated with loss of awareness, falls, injury risk, or clinically significant functional impairment.
Time frame: Baseline, 3, 6, 9, 12 and 21 months post-implant
Percentage of Participants With at Least a 50% Reduction in Disabling Seizure Frequency
Percentage of participants whose 28-day disabling seizure frequency is at least 50% lower than baseline during each post-baseline assessment interval.
Time frame: Baseline, 3, 6, 9, 12 and 21 months post-implant
Percentage of Participants Free of Disabling Seizures
Percentage of participants with no diary-recorded disabling seizures during each post-baseline assessment interval.
Time frame: Baseline, 3, 6, 9, 12 and 21 months post-implant
Change in Liverpool Seizure Severity Scale 2.0 Total Score
The Liverpool Seizure Severity Scale 2.0 is a patient-reported measure of the severity of the participant's most severe seizure during the previous 4 week period. The revised scoring system uses responses to 12 ictal and postictal severity items to calculate a single score that is linearly transformed to a scale from 0 to 100. A score of 0 represents no seizures and a score of 100 represents the most severe possible seizure; higher scores indicate greater seizure severity. A decrease from baseline indicates improvement.
Time frame: Baseline, 3, 6, 9, 12 and 21 months post-implant
Change in Quality of Life in Epilepsy-31 Total Score
The Quality of Life in Epilepsy-31 is a 31-item, patient-reported measure of epilepsy-specific health-related quality of life. It includes seven multi-item scales: seizure worry, overall quality of life, emotional well-being, energy/fatigue, cognitive functioning, medication effects, and social functioning. Item responses are converted to 0-to-100 scale scores according to the QOLIE-31 scoring manual. The overall score is calculated as a weighted average of the seven multi-item scale scores and ranges from 0 to 100. Higher scores indicate better health-related quality of life; a positive change from baseline indicates improvement.
Time frame: Baseline, 3, 6, 9, 12 and 21 months post-implant
Change in NIH Toolbox Flanker Inhibitory Control and Attention Test Score
The NIH Toolbox Flanker Inhibitory Control and Attention test measures attention and inhibitory control by requiring the participant to indicate the direction of a central target while ignoring flanking stimuli that may be congruent or incongruent. The computed score combines response accuracy and reaction time and ranges from 0 to 10. When accuracy is below 80%, the computed score is based on accuracy alone; when accuracy is 80% or higher, accuracy and reaction time are combined. Higher scores indicate better performance, reflecting greater accuracy and, among sufficiently accurate responses, faster reaction time; a positive change from baseline indicates improvement.
Time frame: Baseline, 3, 6, 9, 12 and 21 months post-implant
Change in Free Recall Memory Score
Change from baseline in the number of protocol-specified proper nouns correctly recalled from a 12-item list. Scores range from 0 to 12; higher scores indicate better free recall.
Time frame: Baseline, 3, 6, 9, 12 and 21 months post-implant
Change in NIH Toolbox Picture Sequence Memory Test Score
The NIH Toolbox Picture Sequence Memory Test is an examiner-administered measure of episodic memory. The participant views an ordered series of pictures and then reconstructs the sequence. 1 point is awarded for each pair placed in the correct relative order; higher scores indicate better memory and a positive change indicates improvement.
Time frame: Baseline, 3, 6, 9, 12 and 21 months post-implant
Change in NIH Toolbox Picture Vocabulary Test score
The NIH Toolbox Picture Vocabulary Test is a computer-adaptive measure of receptive vocabulary. The participant hears a word and selects the picture that best matches it from four choices; subsequent items are selected based on prior responses. Responses are scored using item-response theory to estimate vocabulary ability. Higher scores indicate better receptive vocabulary, and a positive change from baseline indicates improvement.
Time frame: Baseline, 3, 6, 9, 12 and 21 months post-implant
Change in Beck Depression Inventory Total Score
The Beck Depression Inventory-II (BDI-II) is a 21-item, self-reported measure of depressive symptoms experienced during the past 2 weeks. Each item is rated from 0 to 3, and item ratings are summed to produce a total score from 0 to 63. Higher scores indicate greater depressive symptom severity. Common interpretive ranges are 0-13, minimal; 14-19, mild; 20-28, moderate; and 29-63, severe. A negative change from baseline indicates improvement.
Time frame: Baseline, 3, 6, 9, 12 and 21 months post-implant
Change in Beck Anxiety Inventory Total Score
The Beck Anxiety Inventory (BAI) is a 21-item, self-reported measure of anxiety symptoms experienced during the past week. Each item is rated from 0 (not at all) to 3 (severely), and item ratings are summed to produce a total score from 0 to 63. Higher scores indicate greater anxiety symptom severity. Common interpretive ranges are 0-7, minimal anxiety; 8-15, mild anxiety; 16-25, moderate anxiety; and 26-63, severe anxiety. A negative change from baseline indicates improvement.
Time frame: Baseline, 3, 6, 9, 12 and 21 months post-implant
Number of Participants With a Device Performance Event
Number of participants with at least one device malfunction, technical problem, lead or system revision, explant, or permanent discontinuation of stimulation attributable to device performance.
Time frame: Post-implementation through 21 months
Change in Epworth Sleepiness Scale Total Score
The Epworth Sleepiness Scale (ESS) is an 8-item, self-reported measure of usual daytime sleep propensity in common situations. Each situation is rated from 0 (would never doze) to 3 (high chance of dozing), and item ratings are summed to produce a total score from 0 to 24. Higher scores indicate greater daytime sleepiness. Common interpretive ranges are 0-10, normal; 11-14, mild sleepiness; 15-17, moderate sleepiness; and 18-24, severe sleepiness. A negative change from baseline indicates improvement.
Time frame: Baseline, 3, 6, 9, 12 and 21 months post-implant
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