Brain Stimulation for Epilepsy

Recruiting at 1 trial location

Overseen By Nitin Tandon, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Nitin Tandon

Disqualifiers: Stroke, Encephalitis, Meningitis, Dementia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 months

8 Participants Needed

Trial Summary

What is the purpose of this trial?

In this study, participants will receive unilateral Deep Brain Stimulation (DBS) for treatment of epilepsy, with network-based stimulation targets specifically defined using a stereo-electro-encephalographic evaluation and chronic recordings using the Medtronic Percept™ primary cell (PC) Neurostimulator DBS System with BrainSense™ Technology. The hypothesis is that, compared to no stimulation or to standard duty cycle high frequency stimulation, epilepsy neuromodulation using low frequency stimulation and informed by network architecture in patients with epilepsy that arises in a hippocampus that also subserves memory - epilepsy in a precious hippocampus (EPH) - will result in a significant decrease in seizure frequency and severity, paralleled by a decrease in EEG spike counts and improved memory function.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that prior vagus nerve stimulation therapy is acceptable if held constant, suggesting some treatments may be continued. It's best to discuss your specific medications with the trial coordinators.

What data supports the effectiveness of the Medtronic Percept PC system with BrainSense Technology for treating epilepsy?

Research on similar devices, like the NeuroPace responsive neurostimulator, shows that electrical brain stimulation can reduce seizure frequency by about half over two years. These devices monitor brain activity and deliver electrical pulses to prevent seizures, suggesting potential effectiveness for the Medtronic Percept PC system as well. ^{1 2 3 4 5}

Is the Medtronic Percept PC system generally safe for use in humans?

The Medtronic Percept PC system, used for deep brain stimulation, is FDA-approved and has been used safely in humans for conditions like Parkinson's disease. While specific safety data for epilepsy is not provided, its approval and use in other conditions suggest it is generally considered safe. ^{6 7 8 9 10}

How does the Medtronic Percept PC system with BrainSense Technology treatment for epilepsy differ from other treatments?

The Medtronic Percept PC system with BrainSense Technology is unique because it offers brain-responsive neurostimulation, which means it can detect abnormal brain activity and deliver electrical stimulation to normalize it. This system is designed to be more precise by using real-time brain data to tailor the treatment to each patient's needs, unlike traditional treatments that do not adapt to ongoing brain activity. ^{2 3 10 11 12}

Research Team

Nitin Tandon, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

This trial is for adults aged 18-65 with Mesial Temporal Lobe Epilepsy who have at least 2 seizures per month but no more than an average of 3 generalized seizures monthly. Participants must speak English, have relatively good memory function, and be able to follow study procedures. Exclusions include severe cognitive impairments, certain brain abnormalities, recent serious psychiatric issues or suicide attempts, pregnancy, and incompatible metal implants.

Inclusion Criteria

Patients with a presumptive diagnosis of EPH determined by the group of clinicians who participate in patient management conference

Proficient in English, as all of our tasks and consent forms will be in English and the inclusion of non-English speakers will introduce another confound in this small sample size and preclude grouped analysis

I am between 18 and 65 years old.

Exclusion Criteria

Patients who have attempted suicide in the past 12 months

Impaired reading and cognitive functions (more than 3 standard deviations below the mean, usually an IQ < 60), as determined by preoperative neuropsychological testing

I have never had non-epileptic spells that could affect seizure detection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive unilateral Deep Brain Stimulation (DBS) for epilepsy treatment, with four 4-month periods of low-frequency DBS stimulation at different sites, followed by a 3-month washout period after each stimulation period.

28 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

Long-term DBS Stimulation

A 7 to 12 month DBS stimulation period with the stimulation type that yielded the best results.

7-12 months

Treatment Details

Interventions

• Medtronic Percept PC system
• Medtronic Percept PC system with BrainSense Technology

Trial Overview The trial tests unilateral Deep Brain Stimulation (DBS) using the Medtronic Percept PC system on patients with epilepsy. It compares low frequency stimulation informed by network architecture against standard high frequency stimulation to see if it reduces seizure frequency and severity while improving memory functions.

Participant Groups

Group I: Site 1, then SOC, then site 2, then SOC, then site 3, then SOC, then site 4, then SOC, then site 4 Experimental Treatment 2 Interventions

Group II: Site 1, then SOC, then site 2, then SOC, then site 3, then SOC, then site 4, then SOC, then site 3 Experimental Treatment 2 Interventions

Group III: Site 1, then SOC, then site 2, then SOC, then site 3, then SOC, then site 4, then SOC, then site 2 Experimental Treatment 2 Interventions

Group IV: Site 1, then SOC, then site 2, then SOC, then site 3, then SOC, then site 4, then SOC, then site 1 Experimental Treatment 2 Interventions

Medtronic Percept PC system is already approved in United States, European Union for the following indications:

Approved in United States as Medtronic Percept PC Neurostimulator for:

• Epilepsy
• Parkinson's disease
• Essential tremor
• Primary dystonia
• Obsessive-compulsive disorder

Approved in European Union as Medtronic Percept PC Neurostimulator for:

• Epilepsy
• Parkinson's disease
• Essential tremor
• Primary dystonia
• Obsessive-compulsive disorder

Who Is Running the Clinical Trial?

Nitin Tandon

Lead Sponsor

Trials

1

Recruited

8+

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

Implantable neurostimulation devices, considered brain-computer interfaces (BCI), are already used in clinical practice to treat challenging neurological disorders, demonstrating their efficacy in targeting both the central and peripheral nervous systems.

Recent advancements in BCI focus on 'closed-loop' systems that use biomarker feedback for personalized therapy, which enhances stimulation delivery while minimizing side effects, indicating a promising direction for future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical neuroprosthetics: Today and tomorrow. Lee, MB., Kramer, DR., Peng, T., et al.[2021]

The NeuroPace responsive neurostimulator, recently approved by the FDA, is an implantable device that monitors brain activity and delivers electrical stimulation to reduce seizures in patients with medically refractory epilepsy.

Initial reports indicate that the device is well tolerated and can reduce seizure frequency by about 50% over a 2-year period, providing a promising new treatment option for patients with limited alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical review of the responsive neurostimulator system for epilepsy. Thomas, GP., Jobst, BC.[2021]

Physical treatments for epilepsy, such as electrical or magnetic stimulators and cooling devices, can be applied externally or implanted, and may help prevent seizures by reducing brain excitability or terminate seizures by disrupting abnormal neuronal activity.

Challenges in clinical trials for these devices include ethical concerns about implantation, difficulties in maintaining blinding, and the need to optimize stimulation parameters to ensure safety and efficacy without causing adverse effects on normal brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Commentary: physical approaches for the treatment of epilepsy: electrical and magnetic stimulation and cooling. Löscher, W., Cole, AJ., McLean, MJ.[2021]

Mike McKenna participated in a clinical trial for the RNS System, an implantable device designed to monitor brain activity and prevent seizures by delivering electrical pulses.

This innovative approach has the potential to significantly improve the quality of life for individuals with epilepsy by actively stopping seizures before they occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlling Seizures with Technology: Researchers Are Working to Predict and Prevent Epileptic Seizures Before They Happen. Bates, M.[2018]

A responsive electrical brain stimulation system was tested in rats to treat seizures, showing significant reduction in seizure amplitude variance when using proportional feedback stimulation, particularly as feedback gain was increased.

The study suggests that the mechanism of seizure suppression may involve shunting of neuronal currents near the electrodes rather than changing neuronal dynamics, indicating potential for further improvements with more complex control algorithms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proportional feedback stimulation for seizure control in rats. Colpan, ME., Li, Y., Dwyer, J., et al.[2007]

The Percept™ PC platform by Medtronic represents a significant advancement in deep brain stimulation (DBS) technology, featuring brain sensing capabilities that allow for real-time monitoring and optimization of therapeutic stimulation.

This device not only enhances patient experience with improved battery life and MRI compatibility but also aims to refine treatment by correlating symptoms with neurophysiological data, although further research is needed to fully establish its clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Device profile of the percept PC deep brain stimulation system for the treatment of Parkinson's disease and related disorders. Jimenez-Shahed, J.[2021]

The Medtronic 'Percept' device, the first FDA-approved deep brain stimulation system with sensing capabilities, was tested on 7 subjects to identify and mitigate artifacts in local field potential signals that could affect its performance.

Using automated template subtraction techniques, researchers successfully removed various artifacts, such as ECG signals and nonphysiologic noise, which could otherwise distort the neural signals and impact the effectiveness of adaptive deep brain stimulation algorithms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Artifact Characterization and a Multipurpose Template-Based Offline Removal Solution for a Sensing-Enabled Deep Brain Stimulation Device. Hammer, LH., Kochanski, RB., Starr, PA., et al.[2023]

The Neuro-Stim System™ devices, used for pain relief through a minimally invasive procedure, have been deemed low-risk by various regulatory bodies, indicating a favorable safety profile.

In a study monitoring 1,207 devices and over 19,000 punctures, the incidence of adverse effects such as bleeding, dermatitis, and infections was quantified, providing valuable data on the safety of this neuromodulation technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimal adverse effects profile following implantation of periauricular percutaneous electrical nerve field stimulators: a retrospective cohort study. Roberts, A., Sithole, A., Sedghi, M., et al.[2020]

In a study involving 12 patients and their caregivers using responsive neurostimulation (RNS) for refractory epilepsy, participants did not report changes in personality or self-perception due to the device, suggesting that concerns about such changes may be overstated.

However, RNS did influence how patients experienced and understood their illness, providing new ways to discuss and conceptualize epilepsy, which highlights the importance of considering the broader social and cultural context of neuroethical issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Closed-Loop Neuromodulation and Self-Perception in Clinical Treatment of Refractory Epilepsy. Haeusermann, T., Lechner, CR., Fong, KC., et al.[2023]

The NeuroPace® RNS® System is a safe and effective neuromodulation device for patients with epilepsy who do not respond to traditional antiseizure medications, providing a nondestructive alternative to surgical resection.

Clinical trials have shown that the RNS System can detect and respond to epileptiform activity by delivering targeted electrical stimulation, which may lead to improved seizure control and could be adapted for other neurological disorders using advanced machine learning techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The RNS System: brain-responsive neurostimulation for the treatment of epilepsy. Jarosiewicz, B., Morrell, M.[2021]

Vagus nerve stimulation is the only method of electrical stimulation for epilepsy that has undergone large, controlled clinical trials, showing its potential as a therapy for intractable epilepsy.

Other forms of electrical stimulation, such as targeting the anterior nuclei of the thalamus and cortical stimulation, are still in the trial phase and are considered experimental, indicating that more research is needed to establish their safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental Electrical Stimulation Therapy for Epilepsy. Oommen, J., Morrell, M., Fisher, RS.[2022]

Brain stimulation techniques, such as responsive neurostimulation and advanced vagus nerve stimulation, are being used to help epilepsy patients who do not respond well to medications, targeting either the seizure origin or key brain areas to reduce seizure severity.

While new transcutaneous stimulation methods are emerging, their effectiveness is still uncertain, highlighting the need for careful evaluation of different neuromodulatory strategies in treating epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain stimulation as a neuromodulatory epilepsy therapy. Schulze-Bonhage, A.[2017]

References

1. Scotland pubmed.ncbi.nlm.nih.gov

Clinical neuroprosthetics: Today and tomorrow. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Critical review of the responsive neurostimulator system for epilepsy. [2021]

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

Commentary: physical approaches for the treatment of epilepsy: electrical and magnetic stimulation and cooling. [2021]

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

Controlling Seizures with Technology: Researchers Are Working to Predict and Prevent Epileptic Seizures Before They Happen. [2018]

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

Proportional feedback stimulation for seizure control in rats. [2007]

6. England pubmed.ncbi.nlm.nih.gov

Device profile of the percept PC deep brain stimulation system for the treatment of Parkinson's disease and related disorders. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Artifact Characterization and a Multipurpose Template-Based Offline Removal Solution for a Sensing-Enabled Deep Brain Stimulation Device. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Minimal adverse effects profile following implantation of periauricular percutaneous electrical nerve field stimulators: a retrospective cohort study. [2020]

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

Closed-Loop Neuromodulation and Self-Perception in Clinical Treatment of Refractory Epilepsy. [2023]

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

The RNS System: brain-responsive neurostimulation for the treatment of epilepsy. [2021]

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

Experimental Electrical Stimulation Therapy for Epilepsy. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Brain stimulation as a neuromodulatory epilepsy therapy. [2017]