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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to precisely delineate human brain networks that modulate respiration and identify specific brain areas and stimulation techniques that can be used to prevent seizure-induced breathing failure.

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 data supports the effectiveness of the treatment for preventing SUDEP in epilepsy?

Research suggests that interventions like rescue breathing and cardiopulmonary resuscitation (CPR) can help manage airway issues and provide oxygen during seizures, potentially reducing the risk of sudden unexpected death in epilepsy (SUDEP). Additionally, monitoring respiratory changes during seizures can help identify when these interventions are needed. ^{1 2 3 4 5}

Is the breathing intervention for SUDEP prevention generally safe for humans?

The safety of breathing interventions like resuscitation techniques has been studied in various contexts, showing that they can be effective in emergency situations to manage respiratory arrest. However, specific safety data for these interventions in the context of SUDEP prevention is limited, and more research is needed to fully understand their safety and effectiveness in this specific application. ^{2 3 6 7 8}

How does the Breathing Rescue treatment differ from other treatments for SUDEP prevention in epilepsy?

Breathing Rescue is unique because it focuses on immediate airway management and resuscitation techniques, like mouth-to-mouth resuscitation, to prevent sudden death during seizures, unlike other treatments that primarily aim to control seizures through medication or surgery. This approach is based on the idea that sudden airway blockage during a seizure can lead to SUDEP, and timely intervention can prevent it. ^{2 3 4 5 9}

Research Team

Nuria L Lecumberri, MD,PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

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

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

Pregnancy

Prisoners

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

References

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

Sudden Unexpected Death in Epilepsy. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Proposed Mechanism-Based Risk Stratification and Algorithm to Prevent Sudden Death in Epilepsy. [2021]

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

From unwitnessed fatality to witnessed rescue: Nonpharmacologic interventions in sudden unexpected death in epilepsy. [2022]

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

A clinical evaluation of a novel algorithm in the reliable detection of epileptic seizures. [2021]

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

Recording respiratory parameters in patients with epilepsy. [2009]

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

DBA/1 mice exhibit chronic susceptibility to audiogenic seizures followed by sudden death associated with respiratory arrest. [2022]

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

Abbreviated report of the NIH/NINDS workshop on sudden unexpected death in epilepsy. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Sudden unexpected death in epilepsy: ongoing challenges in finding mechanisms and prevention. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Can We Prevent Sudden Unexpected Death in Epilepsy (SUDEP)? [2021]