CO2 Chemosensitivity Testing for SUDEP Risk in Epilepsy
Recruiting in Palo Alto (17 mi)
Overseen byBrian Gehlbach, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Iowa
Must not be taking: Opioids
Disqualifiers: Uncontrolled cardiac, pulmonary, hepatic, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The purpose of this research study is to better understand what causes Sudden Unexpected Death in Epilepsy (SUDEP). This study will enroll subjects from the University of Iowa Hospitals and Clinics (UIHC) Epilepsy Monitoring Unit (EMU) and Epilepsy Clinics. The investigators will analyze the effects of seizures on breathing, on the cardiovascular system, and on arousal. The investigators are studying these effects because some cases of SUDEP might be due, in part, to an inability to wake up or sense elevated carbon dioxide (CO2) levels when breathing is impaired. Subjects will be followed for ten years after enrollment to monitor their health.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it does exclude people who are currently using opioids.
What data supports the effectiveness of this treatment for SUDEP risk in epilepsy?
The research suggests that abnormal chemosensing of carbon dioxide (CO2) in the brainstem may be linked to SUDEP risk in epilepsy. Testing CO2 sensitivity could help identify patients at higher risk, although direct evidence of the treatment's effectiveness in reducing SUDEP risk is not provided.
12345Is the 6% CO2/50% O2/N2 gas mixture safe for humans?
The 5% carbon dioxide/95% oxygen mixture has been found to be safe in children with epilepsy, although its effectiveness was limited. However, high levels of oxygen can cause seizures in some people, especially if they have other health issues or are taking certain medications.
24567How does CO2 chemosensitivity testing differ from other treatments for SUDEP risk in epilepsy?
CO2 chemosensitivity testing is unique because it focuses on measuring the body's response to increased carbon dioxide levels to identify patients at higher risk for SUDEP, rather than treating epilepsy directly. This approach is novel as it aims to find biomarkers for SUDEP risk, which currently has no standard treatment.
238910Eligibility Criteria
This trial is for adults aged 18-99 with confirmed or suspected epilepsy, either admitted to the Epilepsy Monitoring Unit (EMU) or receiving care at the University of Iowa Health Care Epilepsy Clinic. It's not suitable for those with uncontrolled heart, lung, liver diseases, progressive neurological conditions not related to epilepsy, current opioid users, pregnant women or those who could become pregnant without effective birth control.Inclusion Criteria
Admission to the EMU for spell characterization (EMU group) or undergoing care in the University of Iowa Health Care Epilepsy Clinic
I have epilepsy.
I am between 18 and 99 years old.
Exclusion Criteria
I am a woman who could become pregnant and have not used effective birth control recently.
I do not have any uncontrolled heart, lung, or liver diseases.
I have difficulty making decisions and do not have someone to help me.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Hospital Admission and Initial Testing
Participants undergo continuous VideoEEG, ECG, and noninvasive cardiorespiratory monitoring during their stay in the Epilepsy Monitoring Unit (EMU) to correlate heart rate and breathing patterns with EEG patterns related to seizures.
5 days
Inpatient stay
Outpatient Testing
Participants undergo repeat HCVR testing up to 4 times over 2 years, with some tests occurring 30 minutes, 2 hours, and 18 hours after seizures.
2 years
4 visits (in-person)
Long-term Follow-up
Participants are monitored annually for ten years through interviews and questionnaires to assess health and ascertain any occurrences of SUDEP.
10 years
Annual interviews (in-person or virtual)
Participant Groups
The study aims to understand what causes Sudden Unexpected Death in Epilepsy (SUDEP) by examining how seizures affect breathing and arousal. Participants will inhale a special gas mixture containing carbon dioxide and oxygen while their health is monitored over ten years.
1Treatment groups
Experimental Treatment
Group I: Respiratory physiology testingExperimental Treatment1 Intervention
Subjects will wear a nosepiece and breathe through a Y-valve that allows switching from room air to two 5-liter rebreathing bags pre-filled with 50% O2, 6% CO2, and balance N2. Ventilation and respiratory gases will be measured using a pneumotachograph and rapid gas analyzers (Ultima PFX pulmonary function/stress testing system, Medical Graphics Corp). In subjects who experience clinical seizure-like activity, we will repeat the HCVR. This repeat test will occur 2 or more hours after a generalized convulsive seizure (GCS). We will repeat the HCVR at least 30 minutes after a non-GCS. Finally, we may repeat the HCVR at least 18 hours after the last seizure (GCS or non-GCS). It is anticipated that some subjects may exhibit frequent seizures that necessitate the adjustment of this schedule. Subjects may also be asked to sniff, hold their breath, and breathe through tubes of different sizes.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Iowa Hospitals and ClinicsIowa City, IA
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Who Is Running the Clinical Trial?
University of IowaLead Sponsor
References
Ictal central apnea as a predictor for sudden unexpected death in epilepsy. [2011]Epidemiological evidence associating ictal hypoventilation during focal seizures with a heightened risk for subsequent sudden unexpected death in epilepsy (SUDEP) is lacking. We describe a patient with temporal lobe epilepsy with two focal seizures recorded in the epilepsy monitoring unit that were associated with central apnea lasting 57 and 58 seconds. During these events, she demonstrated oxygen desaturation down to 68 and 62%. The patient subsequently died at home from autopsy-confirmed SUDEP. The family was not alerted of any seizure activity by the auditory alarm system in her room nor by sleeping in the adjacent room with open doors. This case emphasizes the fact that ictal hypoxia and SUDEP may occur in seizures without noticeable convulsive activity. The report gives credibility to the growing body of literature suggesting that epilepsies affecting the autonomic nervous system may predispose to SUDEP independent of the effects of a secondary generalized convulsion.
Functional MRI Correlates of Carbon Dioxide Chemosensing in Persons With Epilepsy. [2023]Label="Objectives" NlmCategory="UNASSIGNED">Sudden unexpected death in epilepsy (SUDEP) is a catastrophic epilepsy outcome for which there are no reliable premortem imaging biomarkers of risk. Percival respiratory depression is seen in monitored SUDEP and near SUDEP cases, and abnormal chemosensing of raised blood carbon dioxide (CO2) is thought to contribute. Damage to brainstem respiratory control and chemosensing structures has been demonstrated in structural imaging and neuropathological studies of SUDEP. We hypothesized that functional MRI (fMRI) correlates of abnormal chemosensing are detectable in brainstems of persons with epilepsy (PWE) and are different from healthy controls (HC).
Ventilatory response to CO2 in patients with epilepsy. [2021]Label="OBJECTIVE">Severe periictal respiratory depression is thought to be linked to risk of sudden unexpected death in epilepsy (SUDEP) but its determinants are largely unknown. Interindividual differences in the interictal ventilatory response to CO2 (hypercapnic ventilatory response [HCVR] or central respiratory CO2 chemosensitivity) may identify patients who are at increased risk for severe periictal hypoventilation. HCVR has not been studied previously in patients with epilepsy; therefore we evaluated a method to measure it at bedside in an epilepsy monitoring unit (EMU) and examined its relationship to postictal hypercapnia following generalized convulsive seizures (GCSs).
The effect of carbamazepine and ethosuximide on hyperoxic seizures. [2019]The main manifestations of CNS oxygen toxicity are generalized tonic-clonic seizures. We tested the protective effect of 2 antiepileptic drugs, carbamazepine and ethosuximide, which are commonly used for the treatment of generalized seizures, on hyperbaric oxygen-induced convulsions. Rats implanted with chronic cortical electrodes for continuous EEG monitoring were injected i.p. with either carbamazepine (5 doses in the range of 1.5-50 mg/kg), ethosuximide (400 mg/kg), or their vehicles (40% propylene glycol and saline, respectively). The rats were exposed to 5 ATA (0.5 MPa) oxygen. The duration of the latency until the appearance of electrical discharges in the EEG was used as an index of toxicity. Ethosuximide did not protect against hyperoxic seizures. In contrast, rats pretreated (30 min) with carbamazepine exhibited a dose-related protective effect against hyperoxically induced seizures. The results of our study suggest that carbamazepine should be considered for prevention of oxygen-induced seizures during hyperbaric oxygen therapy.
Symptoms of central nervous system oxygen toxicity during 100% oxygen breathing at normobaric pressure with increasing inspired levels of carbon dioxide: a case report. [2021]The greatest danger faced by divers who use oxygen-enriched gas mixtures is central nervous system oxygen toxicity (CNS-OT). CNS-OT is characterised by convulsions resembling grand-mal epileptic seizures, which may terminate in drowning and death. Elevated arterial levels of carbon dioxide (CO₂) (hypercapnia) represent a major risk factor for CNS-OT when breathing hyperoxic gas mixtures. To reduce the risk of a diver being involved in a CNS-OT incident due to hypercapnia, candidates for combat diving are examined at our institute using a routine physiological training procedure, in which they are tested for CO₂ detection and retention. We present the case of a candidate for combat diving, who unexpectedly exhibited signs typical of CNS-OT while breathing pure oxygen under normobaric conditions with > 3 kPa inspired CO₂. Severe headache and nausea, as well as facial muscle twitching, appeared during one of these routine tests. Subsequent medical examination including neurological tests, magnetic resonance imaging and an electroencephalogram were unremarkable. To the best of our knowledge, an event such as this has never previously been published in the medical literature. We present a discussion of the case, and a review of the relevant literature regarding CO₂ as a risk factor for the development of CNS-OT.
5% Carbon Dioxide is safe but of limited efficacy as a treatment for paediatric non-convulsive status epilepticus: An open label observational study. [2018]To establish the efficacy and tolerability of inhaled 5% carbon dioxide/95% oxygen as a treatment for paediatric non-convulsive status epilepticus (NCSE).
Risk factors for oxygen toxicity seizures in hyperbaric oxygen therapy: case reports from multiple institutions. [2013]Oxygen toxicity seizures are a rare but recognized complication of hyperbaric oxygen (HBO2) therapy. Many patients undergoing HBO2 therapy have medical conditions or are taking medications that could contribute to seizures. Previous literature has not extensively reported on these factors in patients experiencing oxygen toxicity seizures. We conducted a chart review at several hyperbaric oxygen centers in the Milwaukee, Wisc., area to explore whether the patients who experienced seizures in the hyperbaric chamber had other medical comorbidities or were on medications which lowered their seizure threshold, thereby contributing to oxygen toxicity seizures. There were a total of seven cases of seizures in five patients. Each patient had risk factors for seizures, including hypercapnia secondary to chronic obstructive pulmonary disease, narcotic withdrawal, alcohol dependence, and antidepressant, tramadol or cephalosporin/ceftriaxone use. We hypothesize that patients who experience oxygen toxicity seizures may have other factors which contribute to the development of these seizures.
Ictal activation of oxygen-conserving reflexes as a mechanism for sudden death in epilepsy. [2023]To test the hypothesis that death with physiological parallels to human cases of sudden unexpected death in epilepsy (SUDEP) can be induced in seizing rats by ictal activation of oxygen-conserving reflexes (OCRs).
Respiratory changes with seizures in localization-related epilepsy: analysis of periictal hypercapnia and airflow patterns. [2010]The rate of sudden unexpected death in epilepsy (SUDEP) approaches 9 per 1,000 patient-years in patients with refractory epilepsy. Respiratory causes are implicated in SUDEP. We reported that ictal hypoxemia occurs in one-third of seizures in localization-related epilepsy. We now report on respiratory changes in the ictal/postictal period including changes in end-tidal CO₂ (ETCO₂) that correlate directly with alveolar CO(2) , allowing a precise evaluation of seizure-related respiratory disturbances.
Biomarkers for SUDEP: Are We There Yet? [2020]Postconvulsive Central Apnea as a Biomarker for Sudden Unexpected Death in Epilepsy (SUDEP) Laura Vilella, MD, Nuria Lacuey, MD, Johnson P. Hampson, MSBME, M. R. Sandhya Rani, PhD, Rup K. Sainju, MBBS, Daniel Friedman, MD, Maromi Nei, MD, Kingman Strohl, MD, Catherine Scott, MPhil, Brian K. Gehlbach, MD, Bilal Zonjy, MD, Norma J. Hupp, Anita Zaremba, BA, Nassim Shafiabadi, MD, Xiuhe Zhao, MD, Victoria Reick-Mitrisin, MS, Stephan Schuele, MD, MPH, Jennifer Ogren, PhD, Ronald M. Harper, PhD, Beate Diehl, MD, PhD, FRCP, Lisa Bateman, MD, Orrin Devinsky, MD, George B. Richerson, MD, PhD, Philippe Ryvlin, MD, PhD, and Samden D. Lhatoo, MD, FRCP. Neurology. 2019;92:e171-e182.