EpilepsyNCT04134754
Carbon Dioxide (CO2) Chemosensitivity and SUDEP
A study testing 6% Carbon dioxide/50% oxygen/balance nitrogen mixture in people with Epilepsy and SUDEP, run by University of Iowa at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- What is being tested?
- 6% Carbon dioxide/50% oxygen/balance nitrogen mixture
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 335 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Dec 2019to 1 Oct 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The subject is between 18 and 99 years of age.
- Confirmed or suspected epilepsy.
- Admission to the EMU for spell characterization (EMU group) or undergoing care in the University of Iowa Health Care Epilepsy Clinic.
Who cannot join
- History of uncontrolled cardiac, pulmonary, or hepatic disease.
- Progressive or uncontrolled neurologic disease unrelated to epilepsy.
- Current opioid use.
- 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).
- Other comorbid condition that may influence the safety or feasibility of HCVR testing.
- Limited decision-making capacity and absence of a qualified representative.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Deidre Dragon, BS, (319) 356-4337, dragond@uiowa.edu
Brian K Gehlbach, MD, 319-356-3603, brian-gehlbach@uiowa.edu
About this study
Official title: The Role of Central CO2 Chemosensitivity in Postictal Respiratory Depression and SUDEP
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.
Read the 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.
- Being tested
- 6% Carbon dioxide/50% oxygen/balance nitrogen mixture
- Keywords
- Epilepsy
- Medical subject headings
- Epilepsy, Sudden Unexpected Death in Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
6% Carbon dioxide/50% oxygen/balance nitrogen mixtureOther
In the hypercapnic ventilatory response (HCVR) test, the subject will rebreathe a gas mixture that has 6% carbon dioxide and 50% oxygen. This test has been performed for decades for research and clinical purposes. The effects of carbon dioxide inhalation are short lived and do not cause long term consequences. the hypercapnic ventilatory response (HCVR), we will have you
| Study group | Role | What they receive |
|---|---|---|
| Respiratory physiology testing | Other | 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. Receives: Other: 6% Carbon dioxide/50% oxygen/balance nitrogen mixture |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the correlation between baseline central CO2 chemosensitivity and the increase in transcutaneous CO2 levels after a seizure.
The change in HCVR slope (change in minute ventilation [liters/min] vs change in end tidal CO2 [mm Hg]) will be correlated with the increase in transcutaneous CO2 level (mm Hg) provoked by a seizure.
Measured: Immediately before and after a seizure, variable for each subject but approximately 10 minutes
Determine the correlation between baseline central CO2 chemosensitivity and the duration of transcutaneous CO2 elevation above baseline after a seizure.
The change in HCVR slope (change in minute ventilation [liters/min] vs change in end tidal CO2 [mm Hg]) will be correlated with the duration (minutes) of end tidal CO2 elevation above pre-seizure baseline
Measured: Duration of hospital admission, approximately 5 days
Effect of seizures on HCVR slope (liters/min/mm Hg)
The percent change in HCVR slope (liters/min/mm Hg) from baseline that is induced by a seizure will be measured. The HCVR will be administered at 30 minutes, 2 hours, and 18 hours after nonconvulsive seizures. The HCVR will be administered at 2 hours and 18 hours after convulsive seizures.
Measured: Up to 18 hours after a seizure.
Determine the stability of the HCVR slope over time in patients with epilepsy. of the HCVR over time in patients with epilepsy
The stability of the HCVR slope (liters/min/mm Hg) measured 8 months for 2 years will be assessed using a generalized linear mixed model.
Measured: 2 years
Secondary outcomes (1)
Change in respiratory rate provoked by seizures
Frequency of breaths (breaths/minute) will be measured using respiratory effort belts around the chest and abdomen
Measured: Immediately before and after a seizure, variable for each subject but approximately 10 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2019
- Study start12 Dec 2019
- Primary completion1 Oct 2029 (estimated)
- Study completion1 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Basic Experimental Studies in Humans (BESH)
- Masking
- None (open label)
- Enrolment
- 335 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Brian Gehlbach, University of Iowa
- Investigators
- Brian Gehlbach, MD, Principal investigator, University of IowaGeorge Richerson, MD, PhD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04134754
- Sponsor's protocol ID
- 201908728
- Other IDs
- 1R01NS113764-01
- Status last verified
- Jun 2026
- First submitted
- 8 Oct 2019
- Last updated
- 23 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study data will be shared upon with qualified investigators upon completion of the study, under the guidelines of the NIH Data Sharing Policy and Implementation Guidance and under the control of the Principal Investigators.
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Central CO2 Chemosensitivity in Postictal Respiratory Depression and SUDEP
- ClinicalTrials.gov ID
- NCT04134754
- Acronym / sponsor ID
- 201908728
- Keywords
- Epilepsy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 335 participants (estimated)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 12 Dec 2019 (actual)
- Primary completion
- 1 Oct 2029 (estimated)
- Study completion
- 1 Oct 2029 (estimated)
- First posted
- 22 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Basic Experimental Studies in Humans (BESH)
| Arm | Type | Receives |
|---|---|---|
| Respiratory physiology testing | Other | Other: 6% Carbon dioxide/50% oxygen/balance nitrogen mixtureSubjects 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- The subject is between 18 and 99 years of age.
- Confirmed or suspected epilepsy.
- Admission to the EMU for spell characterization (EMU group) or undergoing care in the University of Iowa Health Care Epilepsy Clinic.
Key exclusion criteria (6 listed)
- History of uncontrolled cardiac, pulmonary, or hepatic disease.
- Progressive or uncontrolled neurologic disease unrelated to epilepsy.
- Current opioid use.
- 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).
- Other comorbid condition that may influence the safety or feasibility of HCVR testing.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 6% Carbon dioxide/50% oxygen/balance nitrogen mixtureIn the hypercapnic ventilatory response (HCVR) test, the subject will rebreathe a gas mixture that has 6% carbon dioxide and 50% oxygen. This test has been performed for decades for research and clinical purposes. The effects of carbon dioxide inhalation are short lived and do not cause long term consequences. the hypercapnic ventilatory response (HCVR), we will have you | Other | Respiratory physiology testing |
Primary outcome
Determine the correlation between baseline central CO2 chemosensitivity and the increase in transcutaneous CO2 levels after a seizure.
Time frame: Immediately before and after a seizure, variable for each subject but approximately 10 minutes
The change in HCVR slope (change in minute ventilation [liters/min] vs change in end tidal CO2 [mm Hg]) will be correlated with the increase in transcutaneous CO2 level (mm Hg) provoked by a seizure.
Determine the correlation between baseline central CO2 chemosensitivity and the duration of transcutaneous CO2 elevation above baseline after a seizure.
Time frame: Duration of hospital admission, approximately 5 days
The change in HCVR slope (change in minute ventilation [liters/min] vs change in end tidal CO2 [mm Hg]) will be correlated with the duration (minutes) of end tidal CO2 elevation above pre-seizure baseline
Effect of seizures on HCVR slope (liters/min/mm Hg)
Time frame: Up to 18 hours after a seizure.
The percent change in HCVR slope (liters/min/mm Hg) from baseline that is induced by a seizure will be measured. The HCVR will be administered at 30 minutes, 2 hours, and 18 hours after nonconvulsive seizures. The HCVR will be administered at 2 hours and 18 hours after convulsive seizures.
Determine the stability of the HCVR slope over time in patients with epilepsy. of the HCVR over time in patients with epilepsy
Time frame: 2 years
The stability of the HCVR slope (liters/min/mm Hg) measured 8 months for 2 years will be assessed using a generalized linear mixed model.
1 secondary outcome
Change in respiratory rate provoked by seizures
Time frame: Immediately before and after a seizure, variable for each subject but approximately 10 minutes
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
- Individual participant dataSharing planned: Yes. Study data will be shared upon with qualified investigators upon completion of the study, under the guidelines of the NIH Data Sharing Policy and Implementation Guidance and under the control of the Principal Investigators.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Brian Gehlbach, MD principal investigator
University of Iowa
George Richerson, MD, PhD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 6% Carbon dioxide/50% oxygen/balance nitrogen mixture in people with Epilepsy and SUDEP, run by University of Iowa at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Coordinator (319-356-4337, dragond@healthcare.uiowa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the correlation between baseline central CO2 chemosensitivity and the increase in transcutaneous CO2 levels after a seizure. (time frame: Immediately before and after a seizure, variable for each subject but approximately 10 minutes). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.