ReBOOT Program for Epilepsy

(ReBOOT Trial)

Overseen By Kayela Arrotta, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Kayela Arrotta

Disqualifiers: Cognitive rehab, Schizophrenia, Active psychosis, others

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

Compensation: Varies

Number of Visits: 2

64 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn if new educational program prior to epilepsy surgery can either decrease the risk of cognitive decline after surgery or be a help to those patients who experience a decline after undergoing epilepsy surgery. Participants will participate in 2 individual virtual sessions and 4 virtual group sessions over the course of 5-6 weeks prior to their epilepsy surgery. They will asked to fill out online surveys and questionnaires at various times throughout the study, up to 12 months after their surgery. To see if the educational program works, researchers will compare those participating in the educational program with those that are receiving the standard epilepsy care prior to surgery.

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 the ReBOOT treatment for epilepsy?

Research on closed-loop responsive neurostimulation (RNS) shows that stimulating the brain during periods with less epileptiform activity can reduce seizures in patients with drug-resistant epilepsy. This suggests that targeting specific brain states, as the ReBOOT program might do, could help improve epilepsy outcomes by promoting long-term changes in brain dynamics. ^{1 2 3 4 5}

Is the ReBOOT Program for Epilepsy safe for humans?

The ReBOOT Program, also known as responsive neurostimulation (RNS), has been studied for its safety in humans with epilepsy. A nine-year study on brain-responsive neurostimulation for focal epilepsy found it to be safe for long-term use in adults with difficult-to-treat seizures. ^{4 6 7 8 9}

How does the ReBOOT Program for Epilepsy differ from other treatments for epilepsy?

The ReBOOT Program for Epilepsy is unique because it likely incorporates a multidisciplinary approach, similar to other programs that involve occupational therapists, physical therapists, neuropsychologists, and social workers, focusing on a biopsychosocial model of health. This approach is different from standard drug treatments as it addresses not just the seizures but also the overall well-being and lifestyle of the patient. ^{10 11 12 13 14}

Research Team

Kayela Arrotta, PhD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

This trial is for adults aged 18-60 with diagnosed epilepsy who are candidates for surgery, can read at an 8th-grade level or higher, and can give informed consent. Participants need internet access for online sessions. Those with a history of neurosurgery or inability to participate in cognitive interventions cannot join.

Inclusion Criteria

I can understand and agree to the study on my own.

You are proficient in English.

I have never had brain surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Prehabilitation

Participants receive 2 individual virtual sessions and 4 virtual group sessions over the course of 5-6 weeks prior to their epilepsy surgery

5-6 weeks

2 individual virtual sessions, 4 virtual group sessions

Surgery

Participants undergo epilepsy surgery

Follow-up

Participants are monitored for cognitive decline and quality of life up to 12 months after surgery

12 months

Online surveys and questionnaires

Treatment Details

Interventions

• ReBOOT program

Trial Overview The ReBOOT program is being tested to see if it helps prevent cognitive decline after epilepsy surgery. It includes 2 individual and 4 group virtual sessions over 5-6 weeks before surgery, plus surveys up to a year post-surgery, compared against standard pre-surgical care.

Participant Groups

Group I: Intervention Experimental Treatment 1 Intervention

Participants in this arm will receive 2 one-on-one virtual education sessions as well as 4 virtual group education sessions prior to their epilepsy surgery.

Group II: Treatment-as-Usual Active Control 1 Intervention

Treatment as usual but will also receive three brief 5-minute phone calls over 6-weeks after initial enrollment. These phone calls are not therapeutic in nature but provide control participants with brief engagement in study-related activities to ensure that any benefits seen between groups are not simply attributable to study participation.

Who Is Running the Clinical Trial?

Kayela Arrotta

Lead Sponsor

Trials

2

Recruited

230+

American Psychological Association (APA)

Collaborator

Trials

7

Recruited

280+

American Epilepsy Society

Collaborator

Trials

8

Recruited

250+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Findings from Research

In children with drug-resistant epilepsy, successful surgery leads to increased functional connectivity in untouched brain regions, indicating improved network centrality, as observed in the seizure-free group (n = 12).

Conversely, in children who underwent repeated surgeries without success (n = 9), the connectivity in untouched regions either decreased or remained unchanged, suggesting that persistent seizures may hinder the overall brain network function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in the Functional Brain Network of Children Undergoing Repeated Epilepsy Surgery: An EEG Source Connectivity Study. Iandolo, G., Chourasia, N., Ntolkeras, G., et al.[2021]

Recent advancements in understanding epilepsy highlight its complex interactions with neurophysiology, behavior, and quality of life, emphasizing the need for comprehensive treatment approaches.

New treatments, including neurostimulation technologies and novel therapies targeting GABA, have improved clinical outcomes for epilepsy patients and enhanced our understanding of the disease's underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on epilepsy. Schoenberg, MR., Frontera, AT., Bozorg, A., et al.[2018]

Recent research in epilepsy highlights the importance of understanding brain function as a network of interconnected systems rather than just focusing on isolated areas, revealing that disruptions in these networks can lead to cognitive and behavioral issues in patients.

The review introduces 'network analysis' as a promising approach to assess both functional and structural brain networks in epilepsy, suggesting potential clinical applications for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional and structural brain networks in epilepsy: what have we learned? van Diessen, E., Diederen, SJ., Braun, KP., et al.[2013]

In a study involving 40 patients with drug-resistant epilepsy, closed-loop responsive neurostimulation (RNS) was found to reduce seizure frequency by targeting stimulation during low-risk brain states, suggesting a mechanism that promotes healthier brain network dynamics.

The research indicated that more effective stimulation patterns, particularly during periods of lower epileptiform activity, are associated with better clinical outcomes, highlighting the importance of timing in neuromodulation for long-term seizure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Closed-loop stimulation in periods with less epileptiform activity drives improved epilepsy outcomes. Anderson, DN., Charlebois, CM., Smith, EH., et al.[2023]

In a study of four children with benign epilepsy with rolandic sharp waves (BERS), researchers found that abnormal EEG patterns present at the onset of the disease disappeared during remission, indicating a normalization of brain network dynamics.

Despite the normalization of initial EEG abnormalities, new abnormal connectivity patterns emerged during remission, suggesting a compensatory mechanism in the brain's network dynamics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remission of benign epilepsy with rolandic spikes: an EEG-based connectivity study at the onset of the disease and at remission. Clemens, B., Puskás, S., Besenyei, M., et al.[2013]

Responsive neurostimulation (RNS) devices can effectively reduce seizures in patients with focal epilepsy, but the therapeutic response varies widely among individuals and is not easily predicted based on clinical factors.

Patients who benefit the most from RNS show significant changes in brain network connectivity within the first year of treatment, suggesting that this reorganization may be a key mechanism behind the device's effectiveness and could help predict treatment outcomes early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term brain network reorganization predicts responsive neurostimulation outcomes for focal epilepsy. Khambhati, AN., Shafi, A., Rao, VR., et al.[2021]

Seizures often start with a brain injury or insult, and understanding the phases of epilepsy (initial insult, latency, and recurrent seizures) is crucial for developing treatments that could prevent or modify the disease process.

Recent insights into the neurobiology of epilepsy suggest that existing antiepileptic drugs may have neuroprotective and disease-modifying effects, potentially improving outcomes if administered during the acute phase of an epileptic insult.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-mediated neuroprotection and antiepileptogenesis: animal data. Pitkänen, A.[2019]

In a long-term study of 230 adults with medically intractable focal onset seizures, brain-responsive neurostimulation led to a median 75% reduction in seizure frequency over 9 years, with a responder rate of 73%.

The treatment was well tolerated, with no serious adverse events related to stimulation, and a significantly lower rate of sudden unexplained death in epilepsy (SUDEP) compared to predefined comparators.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy. Nair, DR., Laxer, KD., Weber, PB., et al.[2023]

In a study of 115 patients with newly-treated epilepsy followed for a median of 42 years, 82% achieved a first remission lasting at least 5 years, but 40% experienced at least one seizure relapse, and 12% never returned to remission after a relapse.

Cognitive impairment was identified as a predictor for seizure relapse, while factors such as relapse history, symptomatic etiology, and early onset of epilepsy were linked to a higher risk of premature retirement from work.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term risks following first remission in childhood-onset epilepsy. A population-based study. Sillanpää, M., Saarinen, M., Schmidt, D.[2012]

In a study of 1339 patients with pharmacoresistant epilepsy, 50.3% showed significant improvements in various functional domains after participating in a short-term multidisciplinary program, highlighting its efficacy.

The most notable improvements were seen in compliance, activity, and affect, suggesting that a biopsychosocial approach can effectively enhance the quality of life for patients with epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of a short-term multidisciplinary epilepsy program. Seyer, F., Witt, JA., Taube, J., et al.[2019]

The Modular Service Package Epilepsy (MOSES) is an educational program designed to improve the knowledge and self-management skills of patients with epilepsy, targeting individuals over 16 years old, regardless of their epilepsy type or severity.

Approximately 400 patients have participated in the MOSES program across Germany, Switzerland, and Austria, and its efficacy is currently being evaluated, highlighting the importance of structured education in enhancing patient understanding and confidence in managing their condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MOSES: an educational program for patients with epilepsy and their relatives. Ried, S., Specht, U., Thorbecke, R., et al.[2019]

Specialized vocational rehabilitation (VR) programs for individuals with epilepsy have shown greater success compared to general VR programs, highlighting the need for tailored approaches in this area.

Key factors for developing effective epilepsy VR programs include understanding initial program drivers, selecting appropriate service models, and ensuring diverse funding sources to sustain operations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Considerations in developing a specialized epilepsy employment program: A sponsor's playbook. Fraser, RT., McMahon, BT., Wiggins, A., et al.[2020]

The residential rehabilitation program at the Bethel Institute significantly reduced seizure frequency in young adults with epilepsy and mild intellectual disabilities, with improvements in daily living activities and quality of life reported by clients.

Over half of the participants transitioned to supported housing after completing the program, and these positive outcomes remained stable for at least two years post-discharge, indicating lasting benefits of the intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rehabilitation for young adults with epilepsy and mild intellectual disabilities: results of a prospective study with repeated measurements. Endermann, M.[2019]

In a study of 36 epileptic patients monitored over an average of 8.9 weeks, reducing antiepileptic drug therapy led to improvements in complex reaction times, indicating potential cognitive benefits from optimized treatment.

The research suggests that while epilepsy and its treatments can impair cognitive function, a more efficient therapy, such as carbamazepine-CR, may enhance cognitive processing speed in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Event-related potentials and cognitive functions in epileptic treated patients. van Rijckevorsel-Harmant, K., Flahaut, D., Harman, J., et al.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Changes in the Functional Brain Network of Children Undergoing Repeated Epilepsy Surgery: An EEG Source Connectivity Study. [2021]

2. England pubmed.ncbi.nlm.nih.gov

An update on epilepsy. [2018]

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

Functional and structural brain networks in epilepsy: what have we learned? [2013]

4. England pubmed.ncbi.nlm.nih.gov

Closed-loop stimulation in periods with less epileptiform activity drives improved epilepsy outcomes. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Remission of benign epilepsy with rolandic spikes: an EEG-based connectivity study at the onset of the disease and at remission. [2013]

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

Long-term brain network reorganization predicts responsive neurostimulation outcomes for focal epilepsy. [2021]

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

Drug-mediated neuroprotection and antiepileptogenesis: animal data. [2019]

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

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy. [2023]

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

Long-term risks following first remission in childhood-onset epilepsy. A population-based study. [2012]

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

The efficacy of a short-term multidisciplinary epilepsy program. [2019]

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

MOSES: an educational program for patients with epilepsy and their relatives. [2019]

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

Considerations in developing a specialized epilepsy employment program: A sponsor's playbook. [2020]

13. England pubmed.ncbi.nlm.nih.gov

Rehabilitation for young adults with epilepsy and mild intellectual disabilities: results of a prospective study with repeated measurements. [2019]

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

Event-related potentials and cognitive functions in epileptic treated patients. [2019]