DBS Therapy for Epilepsy

(EPAS Trial)

Recruiting at 12 trial locations

Overseen By Jim Vollhaber

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: MedtronicNeuro

Must be taking: Antiepileptic drugs

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: Generalized epilepsy, Psychogenic seizures, others

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

140 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this post-approval study is to further evaluate the long-term safety and effectiveness of Medtronic DBS therapy for epilepsy on seizure reduction in newly implanted participants through 3 years of follow-up.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not be on certain medications like antiplatelet or anticoagulant drugs before surgery. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment Medtronic DBS Therapy for Epilepsy?

Research shows that deep brain stimulation (DBS) can help reduce seizures in people with epilepsy that doesn't respond to medication. Studies have found that targeting specific brain areas with DBS can decrease the abnormal brain activity that causes seizures, and a large trial showed it was effective for certain types of seizures. ^{1 2 3 4 5}

Is DBS therapy generally safe for humans?

Deep brain stimulation (DBS) has been studied for over 30 years and is considered generally safe for treating epilepsy, with risks mainly involving bleeding and infection. Clinical trials and studies have shown that DBS can be a safe option for people with epilepsy that doesn't respond to medication. ^{5 6 7 8 9}

How is DBS Therapy for Epilepsy different from other treatments?

DBS Therapy for Epilepsy is unique because it involves implanting a device that sends electrical impulses to specific areas of the brain, like the anterior nucleus of the thalamus, to help control seizures. Unlike medications, which are taken orally, this treatment is minimally invasive and targets the brain directly, offering an option for those with epilepsy that doesn't respond to drugs. ^{2 3 5 6 10}

Eligibility Criteria

This study is for adults with epilepsy who haven't responded to at least 3 antiepileptic drugs. Participants should have an average of 6 or more partial seizures per month and be able to attend scheduled visits and maintain a seizure diary. People can't join if they've had recent severe seizures, are candidates for surgery, have bleeding risks, substance abuse history, need frequent MRIs, or have other electrical implants.

Inclusion Criteria

I am 18 years old or older.

I have partial onset seizures that might become full-body seizures.

I average 6 or more partial seizures a month, with no 30-day seizure-free periods.

Exclusion Criteria

You have seizures so often that you can't keep track of them every day.

Within the past year, you have been hospitalized for a mental illness, attempted suicide, or experienced symptoms like hearing or seeing things that are not real, not related to seizures or medication.

Currently participating, or plans to participate, in another investigational study unless written approval is provided by the Medtronic study team

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation and Initial Treatment

Participants receive the Medtronic DBS implant and begin initial treatment

12 months

Regular visits for monitoring and adjustment

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Periodic visits for follow-up assessments

Treatment Details

Interventions

• Medtronic DBS Therapy

Trial Overview The trial is testing the long-term safety and effectiveness of Medtronic's Deep Brain Stimulation (DBS) therapy using Activa™ PC and Percept™ PC systems in reducing seizures over three years in those newly implanted with these devices.

Participant Groups

Group I: Active Deep Brain Stimulation (DBS) Experimental Treatment 1 Intervention

Medtronic DBS Therapy is already approved in European Union, United States for the following indications:

Approved in European Union as Medtronic DBS Therapy for Epilepsy for:

• Epilepsy characterized by partial-onset seizures, with or without secondary generalization, that are refractory to three or more antiepileptic medications

Approved in United States as Medtronic DBS Therapy for Epilepsy for:

• Epilepsy characterized by partial-onset seizures, with or without secondary generalization, that are refractory to three or more antiepileptic medications

Who Is Running the Clinical Trial?

MedtronicNeuro

Lead Sponsor

Trials

72

Recruited

20,900+

Geoff Martha

MedtronicNeuro

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Eric Peterson

MedtronicNeuro

Chief Medical Officer since 2020

MD from University of Miami

Findings from Research

A 39-year-old male with progressive myoclonic epilepsy experienced a 50% reduction in seizure intensity and frequency after receiving bilateral deep brain stimulation (DBS) in the subthalamic nucleus (STN), despite previous treatments being ineffective.

This case represents the first documented positive outcome of DBS for progressive myoclonic epilepsy in an adult, suggesting that further studies are needed to determine the best targets for DBS in epilepsy treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic high-frequency deep brain stimulation of the STN/SNr for progressive myoclonic epilepsy. Vesper, J., Steinhoff, B., Rona, S., et al.[2007]

Deep brain stimulation (DBS) is an emerging and powerful treatment option for patients with drug-resistant epilepsy, particularly for those with extratemporal epilepsy.

DBS involves a minimally invasive surgical procedure to implant a pacemaker that electrically stimulates specific brain structures, similar to its established use in treating Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Refractory epilepsy and deep brain stimulation. Pereira, EA., Green, AL., Stacey, RJ., et al.[2011]

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) has shown efficacy in treating partial seizures in epilepsy, particularly in a recent large, double-blind trial focused on the anterior nucleus of the thalamus, indicating its potential clinical utility.

While DBS is a promising palliative treatment for epilepsy, it carries risks such as hemorrhage and infection, and further research is needed to understand its mechanisms and optimize stimulation parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic brain stimulation for epilepsy. Lockman, J., Fisher, RS.[2018]

In a study of 73 deep brain stimulation (DBS) implants for refractory epilepsy, transventricular (TV) lead trajectories were found to have a significantly higher success rate (90%) for placing contacts at the anterior nucleus of thalamus (ANT) compared to extraventricular (EV) trajectories (71%).

The use of TV trajectories also resulted in a higher bilateral success rate (84%) compared to EV trajectories (58%), with no intracranial bleeding reported, indicating that TV trajectories are both more effective and safe for this procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Surgical Approach to the Anterior Nucleus of Thalamus in Patients With Refractory Epilepsy: Experience from the International Multicenter Registry (MORE). Lehtimäki, K., Coenen, VA., Gonçalves Ferreira, A., et al.[2020]

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) has been shown to be effective in reducing seizure frequency in adults with epilepsy that does not respond to multiple medications, based on a randomized trial involving this treatment.

The U.S. Food and Drug Administration has approved DBS therapy for epilepsy as an adjunctive treatment, specifically for patients aged 18 and older with partial onset seizures that are resistant to three or more antiepileptic drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for epilepsy. Salanova, V.[2019]

Deep brain stimulation (DBS) is a promising alternative treatment for patients with epilepsy who do not respond well to antiepileptic drugs, particularly for the 30% of patients with refractory epilepsy.

The review of patient outcomes indicates that DBS can be both safe and effective, with various brain targets such as the thalamic nuclei and hippocampus showing positive results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of deep brain stimulation for the treatment of medically refractory epilepsy. Klinger, NV., Mittal, S.[2016]

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]

In a study of four patients with generalized epilepsy who underwent deep brain stimulation (DBS) of the centro-median thalamus after previous callosal section, all patients experienced a significant reduction in seizure frequency, ranging from 65% to 95%, with no reported complications.

The DBS procedure also improved attention levels in all patients, suggesting that the centro-median thalamus may help modulate epileptic discharges, although it does not appear to be the source of the epileptic activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Centro-median stimulation yields additional seizure frequency and attention improvement in patients previously submitted to callosotomy. Cukiert, A., Burattini, JA., Cukiert, CM., et al.[2014]

References

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

Chronic high-frequency deep brain stimulation of the STN/SNr for progressive myoclonic epilepsy. [2007]

2. Scotland pubmed.ncbi.nlm.nih.gov

Refractory epilepsy and deep brain stimulation. [2011]

3. 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]

4. India pubmed.ncbi.nlm.nih.gov

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

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

Therapeutic brain stimulation for epilepsy. [2018]

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

The Surgical Approach to the Anterior Nucleus of Thalamus in Patients With Refractory Epilepsy: Experience from the International Multicenter Registry (MORE). [2020]

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

Deep brain stimulation for epilepsy. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical efficacy of deep brain stimulation for the treatment of medically refractory epilepsy. [2016]

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

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

10. England pubmed.ncbi.nlm.nih.gov

Centro-median stimulation yields additional seizure frequency and attention improvement in patients previously submitted to callosotomy. [2014]