Clinical trial NCT04134754: Carbon Dioxide (CO2) Chemosensitivity and SUDEP
Official title: The Role of Central CO2 Chemosensitivity in Postictal Respiratory Depression and SUDEP
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Epilepsy
SUDEP
Keywords: Epilepsy
Lead sponsor: University of Iowa
Sponsor class: OTHER
First posted: 2019-10-22
Enrollment: 335
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Basic Experimental Studies in Humans (BESH)
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: In this study, the investigators will only enroll adults with confirmed or suspected epilepsy; there is no control group. Patients admitted to the UIHC Epilepsy Monitoring Unit (EMU) for continuous VideoEEG will undergo video recordings of their face and body, electroencephalography (EEG), and electrocardiogram (ECG) as part of their normal clinical care. Research subjects will undergo noninvasive cardiorespiratory monitoring during their EMU stay for the purpose of correlating heart rate and breathing patterns with EEG patterns related to their seizures.

Eligible subjects will undergo several respiratory tests. This may include sniffing and breath holding and breathing through tubes of different sizes. One test, called the hypercapnic ventilatory response (HCVR), will have you rebreathe a gas mixture of 6% carbon dioxide and 50% oxygen to look at how more you breath in response to the increase in carbon dioxide levels. The investigators will then measure how much more subjects breathe in response to the increase in carbon dioxide levels, and also how breathing feels at the end of the test. The investigators will analyze the relationship between the HCVR and cardiorespiratory changes from seizures. The investigators will also analyze the effect of seizures on the HCVR. The HCVR test will be done by our respiratory therapist during subjects' stay in the EMU.

Some subjects will be asked to participate in repeat testing of the HCVR 3 more times as an outpatient over the next 2 years. Additional subjects will also be enrolled from the clinic and will also undergo HCVR testing 4 times over the 2 years. All subjects will agree to undergo an interview in person or by phone, email, or questionnaire annually for ten years. They will also provide consent for follow-up with a personal contact in the event of subject death, for the purpose of ascertaining whether the death was due to SUDEP.

Eligibility criteria: Inclusion Criteria:

1. The subject is between 18 and 99 years of age.
2. Confirmed or suspected epilepsy.
3. Admission to the EMU for spell characterization (EMU group) or undergoing care in the University of Iowa Health Care Epilepsy Clinic.

Exclusion Criteria:

1. History of uncontrolled cardiac, pulmonary, or hepatic disease.
2. Progressive or uncontrolled neurologic disease unrelated to epilepsy.
3. Current opioid use.
4. Women of child-bearing potential who are pregnant or capable of becoming pregnant (e.g. sexual activity within the past 21 days without a highly effective form of birth control or positive urine pregnancy test).
5. Other comorbid condition that may influence the safety or feasibility of HCVR testing.
6. Limited decision-making capacity and absence of a qualified representative.

Primary outcomes:
measure: Determine the correlation between baseline central CO2 chemosensitivity and the increase in transcutaneous CO2 levels after a seizure.
timeFrame: Immediately before and after a seizure, variable for each subject but approximately 10 minutes
measure: Determine the correlation between baseline central CO2 chemosensitivity and the duration of transcutaneous CO2 elevation above baseline after a seizure.
timeFrame: Duration of hospital admission, approximately 5 days
measure: Effect of seizures on HCVR slope (liters/min/mm Hg)
timeFrame: Up to 18 hours after a seizure.
measure: Determine the stability of the HCVR slope over time in patients with epilepsy. of the HCVR over time in patients with epilepsy
timeFrame: 2 years
Secondary outcomes:
measure: Change in respiratory rate provoked by seizures
timeFrame: Immediately before and after a seizure, variable for each subject but approximately 10 minutes
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
Study officials:
affiliation: University of Iowa
name: Brian Gehlbach, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Iowa
name: George Richerson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: