Brain Activity Monitoring for Epilepsy

Recruiting at 2 trial locations

Overseen By Sameer Sheth, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Disqualifiers: Inability to understand, Epilepsy, others

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

Compensation: Varies

Number of Visits: Unknown

205 Participants Needed

Trial Summary

What is the purpose of this trial?

Humans have a remarkable ability to flexibly interact with the environment. A compelling demonstration of this cognitive flexibility is human's ability to respond correctly to novel contextual situations on the first attempt, without prior rehearsal. The investigators refer to this ability as 'ad hoc self-programming': 'ad hoc' because these new behavioral repertoires are cobbled together on the fly, based on immediate demand, and then discarded when no longer necessary; 'self-programming' because the brain has to configure itself appropriately based on task demands and some combination of prior experience and/or instruction. The overall goal of our research effort is to understand the neurophysiological and computational basis for ad hoc self-programmed behavior. The previous U01 project (NS 108923) focused on how these programs of action are initially created. The results thus far have revealed tantalizing notions of how the brain represents these programs and navigates through the programs. In this proposal, therefore, the investigators focus on the question of how these mental programs are executed. Based on the preliminary findings and critical conceptual work, the investigators propose that the medial temporal lobe (MTL) and ventral prefrontal cortex (vPFC) creates representations of the critical elements of these mental programs, including concepts such as 'rules' and 'locations', to allow for effective navigation through the algorithm. These data suggest the existence of an 'algorithmic state space' represented in medial temporal and prefrontal regions. This proposal aims to understand the neurophysiological underpinnings of this algorithmic state space in humans. By studying humans, the investigators will profit from our species' powerful capacity for generalization to understand how such state spaces are constructed. The investigators therefore leverage the unique opportunities available in human neuroscience research to record from single cells and population-level signals, as well as to use intracranial stimulation for causal testing, to address this challenging problem. In Aim 1 the investigators study the basic representations of algorithmic state space using a novel behavioral task that requires the immediate formation of unique plans of action. Aim 2 directly compares representations of algorithmic state space to that of physical space by juxtaposing balanced versions of spatial and algorithmic tasks in a virtual reality (VR) environment. Finally, in Aim 3, the investigators test hypotheses regarding interactions between vPFC and MTL using intracranial stimulation.

Will I have to stop taking my current medications?

The trial protocol does not specify whether participants must stop taking their current medications.

What data supports the effectiveness of the drug Lacosamide for epilepsy?

Research shows that Lacosamide, when used with other epilepsy drugs, can reduce the frequency of partial-onset seizures. It works by affecting certain proteins and channels in the brain, which helps protect nerve cells and improve brain function. ^{1 2 3 4 5}

Is lacosamide safe for humans?

Lacosamide (also known as Vimpat) is generally well tolerated in humans, with common side effects including dizziness, headache, nausea, and double vision. It has been tested in clinical trials for epilepsy and has a good safety profile when used as an additional treatment for seizures. ^{1 2 6 7 8}

How does the Brain Activity Monitoring for Epilepsy treatment differ from other treatments for epilepsy?

The Brain Activity Monitoring for Epilepsy treatment, using the RNS System, is unique because it involves a brain-responsive neurostimulation device that detects abnormal brain activity and delivers electrical stimulation to prevent seizures. Unlike traditional medications or surgery, this treatment provides continuous monitoring and personalized intervention without affecting cognition or mood. ^{9 10 11 12 13}

Eligibility Criteria

This trial is for male and female epilepsy patients aged between 10 and 64 who are having intracranial electrodes placed for their condition. Participants must be able to understand instructions and concentrate well enough to respond correctly during tasks.

Inclusion Criteria

Undergo placement of intracranial electrodes for clinical characterization of epilepsy

I am between 10 and 64 years old.

Exclusion Criteria

Inability to understand and follow instructions

I struggle to concentrate and often get things wrong because of it.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Behavioral Task Performance

Participants perform novel computerized tasks to assess behavioral performance and accuracy

1-2 weeks

Daily sessions in the Epilepsy Monitoring Unit

Neurophysiological Activity Monitoring

Neural activity is measured using depth electrodes to understand neural representations during tasks

1-2 weeks

Continuous monitoring in the Epilepsy Monitoring Unit

Follow-up

Participants are monitored for safety and effectiveness after task performance

4 weeks

Treatment Details

Interventions

• EMU
• NEUROPACE RNS SYSTEM

Trial Overview The study is examining how the brain responds when creating new behaviors on-the-spot, focusing on specific brain areas: medial temporal lobe (MTL) and ventral prefrontal cortex (vPFC). It involves novel tasks, virtual reality environments, and direct brain stimulation.

Participant Groups

Group I: Neuropace RNS Device Experimental Treatment 1 Intervention

Patients are implanted with RNS device to treat their seizure activity

Group II: Epilepsy Monitoring Unit Experimental Treatment 1 Intervention

Patient's behavioral and neural activity via computer tasks and questionnaires are monitored in the Epilepsy Monitoring Unit

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Findings from Research

In a study of 15 inpatients with frequent partial-onset seizures and cognitive or affective disorders, intravenous lacosamide significantly reduced seizure frequency by 75% in some patients, with 11 out of 15 experiencing no seizures after 2-3 days of treatment.

Lacosamide also positively impacted the emotional well-being and quality of life in 73.4% of patients, with only mild to moderate side effects reported in 2 patients, indicating it is a well-tolerated and effective option for drug-resistant seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of intravenous lacosamide in psychiatric hospital]. Vakula, IN., Bojko, EO., Vorona, UA., et al.[2018]

Lacosamide (Vimpat) is an antiepileptic drug that works through a dual mechanism: it enhances the slow inactivation of voltage-gated sodium channels and modulates the CRMP-2 protein, which is involved in neuroprotection.

Clinical studies have shown that lacosamide effectively reduces seizure frequency in patients with partial-onset seizures when used alongside other antiepileptic medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lacosamide. A new antiepileptic drug as adjunctive therapy in patients with partial-onset seizures]. Saussele, T.[2018]

In a study involving six patients with brain tumor-related epilepsy (BTRE) who completed four months of treatment with lacosamide (LCM), the drug showed good efficacy in seizure control, with one patient becoming seizure-free and four experiencing a reduction in seizure frequency by 50% or more.

Lacosamide had only a mild effect on EEG background activity, indicating that it may not significantly alter brain function while still providing therapeutic benefits for seizure management in BTRE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacosamide on background eeg activity in brain tumor-related epilepsy patients: A case series study. Maschio, M., Zarabla, A., Maialetti, A., et al.[2021]

Lacosamide was generally well tolerated in adults with cerebrovascular epilepsy etiology (CVEE), with common treatment-emergent adverse events including headache, dizziness, and fatigue, reported by 74.1% of patients on lacosamide.

In terms of efficacy, a higher proportion of patients on lacosamide completed 6 and 12 months of treatment without seizures compared to those on carbamazepine-CR, and during monotherapy, 56.7% of patients were 50% responders, with 20% achieving seizure freedom.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacosamide in patients with epilepsy of cerebrovascular etiology. Rosenow, F., Brandt, C., Bozorg, A., et al.[2020]

A dosing scheme using valproate sodium injection (VPA-IV) followed by divalproex sodium extended-release (VPA-ER) was developed for 42 patients in an epilepsy monitoring unit, allowing for rapid initiation of therapy without increasing seizure risk.

The treatment was well tolerated, with only mild side effects reported, and all patients showed improved seizure control within a week after discharge, indicating the efficacy of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful initiation of combined therapy with valproate sodium injection and divalproex sodium extended-release tablets in the epilepsy monitoring unit. Boggs, JG., Preis, K.[2013]

Lacosamide is effective as both monotherapy (in the USA) and adjunctive therapy for focal seizures in adults and adolescents, showing significant reductions in seizure rates compared to placebo in clinical trials.

Patients can safely switch from oral to intravenous lacosamide therapy at the same dosage, making it a flexible treatment option, especially when oral administration is not feasible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacosamide: A Review in Focal Seizures in Patients with Epilepsy. Scott, LJ.[2018]

In a study of 21 epilepsy patients taking lacosamide, the concentration of the drug in cerebrospinal fluid (CSF) was found to be approximately 85% of that in serum, indicating that serum levels can effectively reflect CNS exposure.

The study demonstrated a strong correlation between CSF and serum concentrations of lacosamide, suggesting that monitoring serum levels could be a reliable method for assessing drug exposure in the central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of lacosamide concentrations in cerebrospinal fluid and serum in patients with epilepsy. May, TW., Brandt, C., Helmer, R., et al.[2018]

Lacosamide is an effective antiepileptic drug that works by enhancing sodium channel inactivation and binding to CRMP2, helping to stabilize neuronal membranes and reduce seizures in patients with uncontrolled partial-onset seizures.

In clinical trials, lacosamide was generally well tolerated, with common side effects including dizziness and headache, and it has a favorable pharmacokinetic profile allowing for twice-daily dosing with low potential for drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacosamide for the prevention of partial onset seizures in epileptic adults. Kelemen, A., Halász, P.[2021]

The responsive neurostimulator (RNS) has been clinically used since 2013 to treat patients with medically refractory partial epilepsy, showing significant seizure reduction compared to sham stimulation in a randomized clinical trial.

Long-term use of the RNS has provided valuable data on epilepsy dynamics, including insights into seizure onset patterns and the potential for early detection of treatment benefits, although optimal patient selection and lead placement remain areas for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responsive neurostimulation: Review of clinical trials and insights into focal epilepsy. Geller, EB.[2019]

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]

In a study involving 16 patients with medically refractory focal epilepsy, robotic-assisted implantation of the responsive neurostimulation system (RNS) led to an impressive average seizure reduction of 82% at 6 months and 90% at 1 year, demonstrating its efficacy as a treatment.

The use of the ROSA robot for targeting ictal-onset zones resulted in a highly accurate lead placement, with only a 0.165-mm discrepancy between the expected and actual lead locations, indicating a precise method for improving seizure control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Robotic-Assisted Technique to Implant the Responsive Neurostimulation System. Tran, DK., Paff, M., Mnatsakanyan, L., et al.[2021]

In patients with the RNS System for epilepsy, a significant reduction in 'long episodes' of electrographic seizures within the first week of starting new antiseizure drugs (ASDs) was highly predictive of the medication's efficacy.

In a larger multicenter study, a decrease in 'episode starts' by 50% or more within the first 1-2 weeks was 90% specific for effective medications, suggesting that early neurophysiological data can guide quicker medication adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early detection rate changes from a brain-responsive neurostimulation system predict efficacy of newly added antiseizure drugs. Quraishi, IH., Mercier, MR., Skarpaas, TL., et al.[2021]

The RNS® System offers a promising treatment for patients with refractory partial onset seizures, achieving a 44% reduction in seizures at one year, which improves to 60-66% over three to six years.

This closed-loop brain stimulation method does not negatively affect cognitive function or mood, and the risks associated with the device are comparable to those of other implanted medical devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responsive Direct Brain Stimulation for Epilepsy. Morrell, MJ., Halpern, C.[2022]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The efficacy of intravenous lacosamide in psychiatric hospital]. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

[Lacosamide. A new antiepileptic drug as adjunctive therapy in patients with partial-onset seizures]. [2018]

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

Lacosamide on background eeg activity in brain tumor-related epilepsy patients: A case series study. [2021]

4. Denmark pubmed.ncbi.nlm.nih.gov

Lacosamide in patients with epilepsy of cerebrovascular etiology. [2020]

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

Successful initiation of combined therapy with valproate sodium injection and divalproex sodium extended-release tablets in the epilepsy monitoring unit. [2013]

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

Lacosamide: A Review in Focal Seizures in Patients with Epilepsy. [2018]

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

Comparison of lacosamide concentrations in cerebrospinal fluid and serum in patients with epilepsy. [2018]

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

Lacosamide for the prevention of partial onset seizures in epileptic adults. [2021]

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

Responsive neurostimulation: Review of clinical trials and insights into focal epilepsy. [2019]

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

A Novel Robotic-Assisted Technique to Implant the Responsive Neurostimulation System. [2021]

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

Early detection rate changes from a brain-responsive neurostimulation system predict efficacy of newly added antiseizure drugs. [2021]

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

Responsive Direct Brain Stimulation for Epilepsy. [2022]