Breathing Interventions for SUDEP Prevention in Epilepsy

(BreatheS Trial)

Overseen By Sandhya Rani, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Respiratory, Cardiac, Cerebrovascular, Pregnancy, Prisoners

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

Compensation: Varies

Number of Visits: 2

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how certain brain networks affect breathing and to find ways to prevent breathing problems caused by seizures in people with epilepsy. Researchers are testing a treatment called Breathing Rescue, which involves specific breathing tasks and brain mapping with stimulation, also known as Brain Stimulation Therapy. The trial seeks participants diagnosed with difficult-to-control focal epilepsy who are currently undergoing invasive EEG monitoring at a specific medical center. Individuals with epilepsy who have had trouble managing it may find this trial a good fit. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could improve epilepsy management.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that these breathing interventions are safe for epilepsy patients?

Research shows that breathing rescue techniques, such as mouth-to-mouth resuscitation, help keep airways open and prevent breathing problems during seizures. These methods are generally safe and resemble first aid practices used in emergencies, like CPR, which assists breathing during a heart attack.

Studies on brain mapping with stimulation have found that brain stimulation treatments are safe and can reduce seizures in people with epilepsy. Long-term research indicates that these treatments have a good safety record, with side effects usually being manageable. This makes them a promising option for those seeking new ways to control seizures.

Both breathing rescue and brain stimulation have evidence supporting their safety, making them reasonable options to consider in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Breathing Rescue for SUDEP (Sudden Unexpected Death in Epilepsy) prevention because it explores a new approach by focusing on breathing tasks combined with brain mapping and stimulation. Unlike current treatments that primarily address seizure control through medication like antiepileptic drugs, this method aims to prevent SUDEP by targeting the respiratory system directly. This innovative technique could provide a non-pharmacological option, offering new hope for individuals with epilepsy who are at risk of SUDEP.

What evidence suggests that this trial's treatments could be effective for preventing SUDEP in epilepsy?

Research shows that breathing techniques, such as rescue breathing, can manage breathing problems and provide oxygen during seizures in people with epilepsy. This method aims to prevent breathing failure, a major cause of sudden unexpected death in epilepsy (SUDEP). In this trial, participants will engage in breathing tasks and brain mapping with stimulation. Studies have found that brain stimulation can reduce seizures, particularly in individuals who do not respond to medications. Brain stimulation sends electrical signals to specific brain areas to help control seizures. Together, these methods may help prevent SUDEP by supporting normal breathing and reducing seizures. ^{2 4 6 7 8}

Who Is on the Research Team?

Nuria L Lecumberri, MD,PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for individuals with intractable focal epilepsy who are admitted to the Epilepsy Monitoring Unit at Memorial Hermann-Texas Medical Center for specific brain monitoring procedures. It's not suitable for pregnant women, prisoners, or those with respiratory, cardiac, or cerebrovascular diseases.

Inclusion Criteria

I am admitted to the EMU for a specific epilepsy study.

I have been diagnosed with hard-to-treat focal epilepsy.

Exclusion Criteria

Pregnancy

I have a history of lung, heart, or stroke-related conditions.

Prisoners

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline measurements of breathing parameters and brain activity are taken before stimulation

1 day

1 visit (in-person)

Stimulation

Participants undergo brain stimulation to assess changes in breathing parameters

2 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after stimulation

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brain mapping with stimulation
• Breathing Rescue

Trial Overview

The study aims to map out brain networks that control breathing and find ways to stimulate certain brain areas to prevent breathing failure during seizures using tasks and mapping techniques.

How Is the Trial Designed?

Group I: Breathing tasks and Brain mapping with stimulation Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

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+

Published Research Related to This Trial

In a study of 79 seizures from 37 patients, apnea was observed in all generalized seizures and in 39% of complex partial seizures, indicating significant respiratory changes during seizures.

The findings suggest that central apnea, which lasted an average of 29 seconds, may play a critical role in the risk of sudden unexpected death in epilepsy (SUDEP), particularly following tachycardia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recording respiratory parameters in patients with epilepsy. Walker, F., Fish, DR.[2009]

Sudden Unexpected Death in Epilepsy (SUDEP) is a major risk for young adults with uncontrolled seizures, and recent evidence suggests that airway occlusion during seizures is a critical factor that can lead to this outcome.

To improve first aid for seizures and potentially prevent SUDEP, it is recommended to monitor airway status, recognize ineffective breathing, use the laryngospasm notch maneuver, provide oxygen early, and perform CPR promptly, as these steps can help manage airway issues and reduce the risk of death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proposed Mechanism-Based Risk Stratification and Algorithm to Prevent Sudden Death in Epilepsy. Lucchesi, M., Silverman, JB., Sundaram, K., et al.[2021]

The NIH-sponsored workshop highlighted the importance of educating people with epilepsy about Sudden Unexpected Death in Epilepsy (SUDEP) to potentially improve seizure control and reduce its incidence.

Ongoing research into the cardiac, autonomic, respiratory, and genetic factors associated with SUDEP is crucial, and a collaborative SUDEP Coalition has been established to enhance prevention efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abbreviated report of the NIH/NINDS workshop on sudden unexpected death in epilepsy. Hirsch, LJ., Donner, EJ., So, EL., et al.[2021]

The risk of Sudden Unexpected Death in Epilepsy (SUDEP) can be reduced through aggressive seizure control and nocturnal supervision, which allows for timely intervention during life-threatening events.

Nursing interventions in epilepsy monitoring units, such as repositioning and oxygen administration, have shown promise in reducing complications during seizures, but their effectiveness in outpatient settings remains unstudied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From unwitnessed fatality to witnessed rescue: Nonpharmacologic interventions in sudden unexpected death in epilepsy. Rugg-Gunn, F., Duncan, J., Hjalgrim, H., et al.[2022]

DBA/1 mice serve as a valuable chronic model for studying sudden unexpected death in epilepsy (SUDEP), as they experience generalized convulsive seizures followed by respiratory arrest, with a high incidence of respiratory failure (90-100%) after multiple seizures.

The respiratory arrest in these mice is reversible with resuscitation, and cardiac activity is detectable for several minutes post-arrest, indicating that respiratory failure is the primary cause of death, which allows for the testing of potential preventive treatments for SUDEP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DBA/1 mice exhibit chronic susceptibility to audiogenic seizures followed by sudden death associated with respiratory arrest. Faingold, CL., Randall, M., Tupal, S.[2022]

A novel algorithm using heart rate changes and oxygen saturation levels was developed to detect clinically significant epileptic seizures, showing an impressive sensitivity of 87% in a multicenter trial with 119 participants.

The algorithm successfully identified 683 seizures, including 77 clinically significant ones, with a low false alarm rate of 4.5 per 24 hours, indicating its potential effectiveness in providing timely assistance during seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical evaluation of a novel algorithm in the reliable detection of epileptic seizures. Brotherstone, R., McLellan, A., Graham, C., et al.[2021]

Patients with epilepsy face a significantly higher risk of sudden unexpected death in epilepsy (SUDEP), which is the leading cause of sudden death in this population, highlighting the urgent need for awareness and education about this risk.

The primary mechanisms behind SUDEP include cardiac arrhythmias, respiratory dysfunction, and brainstem arousal system dysfunction, with effective seizure control being the only proven preventive strategy, while other interventions require further research to establish their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sudden unexpected death in epilepsy: ongoing challenges in finding mechanisms and prevention. Ruthirago, D., Julayanont, P., Karukote, A., et al.[2022]

Sudden unexpected death in epilepsy (SUDEP) is a significant cause of death in patients with refractory epilepsy, but effective prevention strategies are currently lacking, with only low-quality evidence supporting nocturnal supervision as a potential preventive measure.

Various strategies have been proposed to reduce the risk of SUDEP, such as seizure detection devices and respiratory monitoring, but none have been conclusively proven to prevent SUDEP, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can We Prevent Sudden Unexpected Death in Epilepsy (SUDEP)? Bhasin, H., Sharma, S., Ramachandrannair, R.[2021]

Sudden unexpected death in epilepsy (SUDEP) accounts for 2-18% of epilepsy-related deaths, with higher risks in young adults aged 20-45, particularly among those with frequent seizures and those not on antiepileptic medications.

Effective strategies to reduce the risk of SUDEP include aggressive seizure control, patient education on medication adherence, and lifestyle modifications to avoid seizure triggers, highlighting the importance of healthcare provider involvement in patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sudden Unexpected Death in Epilepsy. O'Neal, TB., Shrestha, S., Singh, H., et al.[2022]

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