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

Trial Summary

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 data supports the effectiveness of this treatment for epilepsy?

Deep brain stimulation (DBS) has shown promise in reducing seizures for people with epilepsy who do not respond to medication. Studies have demonstrated that DBS can modulate brain circuits and decrease the abnormal brain activity associated with seizures, leading to a reduction in seizure frequency. ^{1 2 3 4 5}

Is deep brain stimulation (DBS) generally safe for humans?

Deep brain stimulation (DBS) has been used in humans for various conditions, including epilepsy and Parkinson's disease. While it is generally considered safe, there can be complications related to the surgery and the device itself, as reported in studies involving a large number of cases. ^{1 5 6 7 8}

How is the DBS treatment for epilepsy different from other treatments?

Deep Brain Stimulation (DBS) for epilepsy is unique because it involves implanting a device that sends electrical impulses to specific brain areas to reduce seizures, especially in patients who do not respond to medications. Unlike traditional treatments, DBS can be adjusted in real-time to optimize its effects, and it offers a reversible and minimally invasive option for managing epilepsy. ^{1 4 5 9 10}

What is the purpose of this trial?

Deep brain stimulation (DBS) is used to treat epilepsy in cases where patients are medically refractory and are not candidates for surgical resection. This therapy has been shown to be effective in seizure reduction, yet very few patients achieve the ultimate goal of seizure freedom. Implantable neural stimulators (INSs) have many parameters that may be adjusted, and could be tuned to achieve very patient specific therapies. This study will develop a platform for stimulation setting optimization based on power spectral density (PSD) measures.

Research Team

Robert McGovern, MD

Principal Investigator

University of Minnesota

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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) 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]

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]

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]

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]

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]

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]

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]

References

1. Netherlands 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. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers. [2022]

3. India pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Treatment of Refractory Epilepsy. [2022]

4. Italy pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for intractabile epilepsy. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Sensing-enabled hippocampal deep brain stimulation in idiopathic nonhuman primate epilepsy. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Brain stimulation for epilepsy--local and remote modulation of network excitability. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for drug-resistant epilepsy. [2018]

8. Austria pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. [2023]

9. India pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Treatment of Refractory Epilepsy. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Effects of hippocampal low-frequency stimulation in idiopathic non-human primate epilepsy assessed via a remote-sensing-enabled neurostimulator. [2018]