DBS Parameter Optimization for Epilepsy

Overseen By Alec Jonason

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Minnesota

Disqualifiers: Severe dementia

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to fine-tune deep brain stimulation (DBS) settings for people with epilepsy who don't respond to medication and can't undergo surgery. The goal is to use implantable neural stimulators (INSs) to reduce seizures and ideally stop them altogether. Participants will receive different stimulation settings to find the best fit for their needs. This trial suits those with hard-to-treat epilepsy who already have a DBS device implanted. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to benefit from these advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that these implantable neural stimulators (INSs) are safe for epilepsy treatment?

Research has shown that deep brain stimulation (DBS) is generally safe for treating epilepsy. In a study with 110 patients, researchers used DBS safely over many years. The FDA has approved it to help reduce seizures in people with difficult-to-treat epilepsy. The treatment is usually well-tolerated, but like any medical procedure, it carries some risks. Most reports highlight that DBS lowers the number of seizures, with an average reduction of 62%. While side effects can occur, they are usually manageable. Overall, DBS has a strong safety record when used for epilepsy. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how to optimize Deep Brain Stimulation (DBS) for epilepsy using different stimulation settings. Unlike traditional epilepsy treatments like anti-seizure medications or resective surgery, this trial focuses on fine-tuning the parameters of already implanted neural stimulators to enhance their effectiveness. By varying the order and type of electrical stimulation, the trial aims to discover the most effective patterns for reducing seizures, potentially offering a more personalized and precise approach to managing epilepsy.

What evidence suggests that this trial's treatments could be effective for epilepsy?

Research shows that deep brain stimulation (DBS) effectively reduces seizures in people whose epilepsy doesn't respond to medication. Studies have found that DBS decreases seizure frequency and duration, with improvements increasing over time. Another review noted that many patients experienced fewer seizures. The well-known SANTE trial reported a 40.4% reduction in seizures with DBS. The FDA has approved DBS for epilepsy, supporting its effectiveness for difficult-to-treat cases. In this trial, participants with already implanted DBS devices will join different stimulation groups to optimize parameters for seizure reduction. ^{1 2 4 5 6}

Who Is on the Research Team?

Robert McGovern, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for patients with epilepsy that doesn't respond to medication and who already have a deep brain stimulator implanted. It's not suitable for individuals with severe dementia as determined by the study investigator.

Inclusion Criteria

My epilepsy does not improve with medication.

Patients who already have a deep brain stimulator in place

Exclusion Criteria

Patients with severe dementia at investigator discretion

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive deep brain stimulation with optimized parameters based on power spectral density measures

12 months

Regular in-clinic visits for parameter adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Implantable Neural Stimulators (INSs)

Trial Overview The study tests how changing settings on an implantable neural stimulator can better control seizures in epilepsy patients. Different orders of stimulation (PS and OS) are being compared to find the most effective parameter adjustments.

How Is the Trial Designed?

Group I: Stimulation Group C Experimental Treatment 1 Intervention

Participants with already implanted DBS will receive stimulation order 1. OS, OS, PS.

Group II: Stimulation Group B Experimental Treatment 1 Intervention

Participants with already implanted DBS will receive stimulation order 1. OS, PS, OS.

Group III: Stimulation Group A Experimental Treatment 1 Intervention

Participants with already implanted DBS will receive stimulation order 1. PS, OS, OS.

Implantable Neural Stimulators (INSs) is already approved in United States, European Union for the following indications:

Approved in United States as Medtronic DBS System for:

• Focal-onset seizures with or without focal to bilateral seizures in adults who have not responded to three or more antiseizure medications

Approved in European Union as Deep Brain Stimulation (DBS) devices for:

• Epilepsy in adults with focal-onset seizures who have not achieved adequate seizure control despite appropriate trials of antiepileptic medication

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

Deep brain stimulation (DBS) targeting the anterior nucleus of thalamus (ANT) for epilepsy can be effectively visualized using 3 T MRI, allowing for better anatomical delineation of the target area.

There is significant individual variation in the location of ANT among patients, making direct targeting more effective than indirect methods; however, microelectrode recording (MER) alone may not provide reliable localization without detailed imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defining the anterior nucleus of the thalamus (ANT) as a deep brain stimulation target in refractory epilepsy: Delineation using 3 T MRI and intraoperative microelectrode recording. Möttönen, T., Katisko, J., Haapasalo, J., et al.[2022]

Deep brain stimulation (DBS) is a safe and effective treatment for refractory epilepsy, as it can modulate brain circuits and reduce the abnormal neuronal activity associated with seizures.

The video outlines the importance of precise surgical planning and targeting of specific brain nuclei (anterior thalamus, centromedian thalamus, and hippocampus) to optimize DBS outcomes, highlighting that each target has unique advantages and challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Treatment of Refractory Epilepsy. de Oliveira, TVHF., Cukiert, A.[2022]

Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT) and hippocampus (HC) has been shown to significantly reduce seizure frequency in drug-resistant epilepsy, with about 50% of patients experiencing a 46%-90% reduction with ANT-DBS and a 48%-95% reduction with HC-DBS.

Approximately 75% of patients receiving stimulation from ANT, HC, or centromedian nucleus of the thalamus (CMT) report at least a 50% reduction in seizures, with factors like the absence of structural brain abnormalities and specific seizure types influencing the effectiveness of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for drug-resistant epilepsy. Li, MCH., Cook, MJ.[2018]

Temporal Interference (TI) stimulation at 130 Hz non-invasively stimulates the hippocampus, leading to increased physiological brain activity (ripples) and decreased harmful brain activity (Fast Ripples and interictal discharges) in mouse models of epilepsy.

TI stimulation shows better penetration into the human hippocampus compared to traditional transcranial current stimulation (TCS), suggesting its potential as a focused therapeutic approach for treating epilepsy without affecting surrounding brain tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers. Acerbo, E., Jegou, A., Luff, C., et al.[2022]

A novel neurostimulator was used to monitor and stimulate a non-human primate with idiopathic epilepsy, allowing for real-time seizure detection and detailed analysis of seizure characteristics.

Low-frequency hippocampal stimulation showed that optimal parameters (2Hz, 150μs pulse width, 4mA current) could suppress seizure activity, but continuous stimulation was less effective than intermittent stimulation, and the effects varied with circadian rhythms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of hippocampal low-frequency stimulation in idiopathic non-human primate epilepsy assessed via a remote-sensing-enabled neurostimulator. Wozny, TA., Lipski, WJ., Alhourani, A., et al.[2018]

Deep brain stimulation (DBS) shows promising results in reducing seizure frequency for various types of epilepsy, particularly with the anterior nucleus of the thalamus (ANT) and responsive neurostimulation (RNS), which have been tested in larger patient groups and achieved strong evidence for efficacy and safety.

While all stimulation targets (ANT, hippocampus formation, and centromedian nucleus of the thalamus) showed encouraging results, ANT stimulation is effective for multifocal seizures, and hippocampus stimulation can help with temporal lobe epilepsy, indicating that different targets may be better suited for specific epileptic syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for intractabile epilepsy. Morace, R., DI Gennaro, G., Quarato, P., et al.[2022]

Deep brain stimulation (DBS) for Parkinson's disease is generally safe, with a low mortality rate of 0.2% and permanent morbidity at 0.6%, but complications such as intracerebral hemorrhage (ICH) and seizures can occur in a small percentage of cases.

The study found that the type of lead used in DBS can influence complications, with Medtronic's leads associated with higher rates of perielectrode brain edema compared to Boston Scientific's, highlighting the need for further research on hardware design to improve safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. Servello, D., Galbiati, TF., Iess, G., et al.[2023]

This study is the first to use a modified deep brain stimulation (DBS) system to record and analyze brain activity in a nonhuman primate with idiopathic epilepsy, providing valuable insights into seizure characteristics and mechanisms.

The research demonstrated that specific stimulation parameters could either suppress or induce seizure activity, highlighting the potential of DBS as a therapeutic option for epilepsy and paving the way for future advancements in this technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensing-enabled hippocampal deep brain stimulation in idiopathic nonhuman primate epilepsy. Lipski, WJ., DeStefino, VJ., Stanslaski, SR., et al.[2015]

Deep brain stimulation (DBS) has shown remarkable safety and efficacy in treating motor diseases, leading to interest in its potential for managing refractory epilepsy.

Experimental evidence suggests that DBS can modulate brain circuits and reduce the neuronal hypersynchronization associated with epileptic activity, although the exact mechanisms of action are still not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Treatment of Refractory Epilepsy. de Oliveira, TVHF., Cukiert, A.[2021]

This study demonstrated that both anterior thalamic and hippocampal Deep Brain Stimulation (DBS) can effectively modulate local field potential activity and reduce network excitability in a large animal model, suggesting potential therapeutic effects for treatment-resistant epilepsy.

The research also showed that closed-loop stimulation, which adjusts based on real-time brain activity, can effectively control network excitability, indicating a promising direction for future epilepsy treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain stimulation for epilepsy--local and remote modulation of network excitability. Stypulkowski, PH., Stanslaski, SR., Jensen, RM., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11791334/

Effect of deep brain stimulation on the severity of seizures ... DBS reduced seizure frequency and duration in DRE over a 6-month follow-up. SSQ decreased progressively over time, indicating long-term ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0920121125001081

Deep brain stimulation for epilepsy: A systematic review ... Our findings demonstrate high responder rates and reductions in seizure frequency for DBS targeting the ANT or CMN of the thalamus with low rates of seizure ...

3. europe.medtronic.com europe.medtronic.com/xd-en/healthcare-professionals/therapies-procedures/neurological/deep-brain-stimulation/indications/epilepsy/clinical-outcomes.html

CLINICAL OUTCOMES: EPILEPSY Deep Brain Stimulation EFFECTIVENESS RESULTS · REDUCED SEIZURE FREQUENCY. DBS for Epilepsy was shown to reduce median seizure frequency, and these results improved over time. · FREEDOM ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12185915/

Deep Brain Stimulation Therapy for Drug-Resistant Epilepsy The seminal SANTE trial provided robust evidence of its efficacy, with an initial median seizure reduction of approximately 40.4% observed ...

5. mayoclinic.org mayoclinic.org/tests-procedures/deep-brain-stimulation/about/pac-20384562

Deep brain stimulation And deep brain stimulation has been approved by the Food and Drug Administration as a treatment to reduce seizures in hard-to-treat epilepsy.

6. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf/P960009S478B.pdf

P960009/S478 Summary of Safety and Effectiveness (SSED) Medtronic's Deep Brain Stimulator (DBS) System was approved for the following ... The Medtronic DBS System for Epilepsy has demonstrated safety and effectiveness.