Carbon Dioxide (CO2) Chemosensitivity and SUDEP

NCT04134754 | Recruiting

• 2 other identifiers: 2019087281R01NS113764-01
• Study Type: interventional
• Target: 335
• Locations: 1 country
• Sites: 1

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.

Conditions

Epilepsy; SUDEP

Keywords

Epilepsy

Outcome Measures

Primary Outcomes (4)

• 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.

  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

  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.

  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.

  2 years

Secondary Outcomes (1)

• Change in respiratory rate provoked by seizures

  Immediately before and after a seizure, variable for each subject but approximately 10 minutes

Study Arms (1)

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.

Other: 6% Carbon dioxide/50% oxygen/balance nitrogen mixture

Interventions

6% Carbon dioxide/50% oxygen/balance nitrogen mixture OTHER

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

Respiratory physiology testing

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Iowa: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

MeSH Terms

Conditions

Epilepsy; Sudden Unexpected Death in Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Brian Gehlbach, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

• George Richerson, MD, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

319-356-4337; dragond@healthcare.uiowa.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: Basic Experimental Studies in Humans (BESH)

Study Record Dates

• First Submitted: October 8, 2019
• First Posted: October 22, 2019
• Study Start: December 12, 2019
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: March 9, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data elements will be potentially eligible for sharing 1 year after the study has been completed and the results have been disseminated via a summary report.
• Access Criteria: Direct communication with the Principle Investigators.

Locations

US (1)