Clinical trial NCT03268590
Conditions: Hyperoxia Hypoxia, Brain Neurobehavioral Manifestations
Keywords: Hyperoxia Hypoxia, Brain
Sponsor: Case Western Reserve University
Start date: 2017-10-02; Completion date: 2018-05-09
Enrollment: 33 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The investigators will conduct a non-randomized clinical trial to examine the effect of pure oxygen breathing on the brain. The study will compare cerebral blood flow, cortical electrical activity, and cognitive performance in 32 persons during room air (21% oxygen) breathing and pure oxygen (100% oxygen) breathing. Subjects will be used as their own controls. The investigators aim to:

1. Determine whether breathing 100% oxygen changes blood flow through the brain. The investigators will learn whether brain blood flow is increased, decreased or stays the same.
2. Determine if changes that might occur in brain blood flow are also accompanied by changes in the brain's electrical activity (EEG).
3. Learn whether changes in the speed at which the brain processes information (cognitive function) accompany changes in brain blood flow and electrical activity that may be seen.

Detailed description:
The investigators will conduct a crossover design clinical trial to compare the effect of room air breathing (21% inspired oxygen) with pure oxygen breathing (100% inspired oxygen) on brain blood flow and cortical electrical activity. The study involves a one-time data collection taking place at University Hospitals Cleveland Medical Center on the Case Western Reserve University campus in Cleveland, Ohio. The investigators will perform neuroimaging (MRI) with electroencephalographic (EEG) cortical network mapping and cognitive assessments in all participants during room air breathing and again while breathing 100% pure oxygen. Oxygen will be delivered through a non-rebreather mask. Arterial blood partial pressure of oxygen (PaO2) will be measured twice, from arterial blood samples drawn during breathing room air prior to the MRI scan and again after 30 minutes of breathing 100% oxygen immediately following neuroimaging. Thus, the investigators will be able to determine if breathing pure oxygen may temporarily change brain blood flow and breathing, leading to changes in cognitive status such as euphoria or slowed reflexes. Information gained in this study may have direct operational relevance by helping us to understand one potential cause of "Unexplained Physiologic Events" that are reported in some aircraft pilots when flying at high altitude. Information gained could lead to development of new gas mixtures for use by personnel working in low oxygen high altitude environments.

Arms: arm 1: Breathing 21% oxygen via non-rebreather face mask followed by breathing 100% oxygen via non-rebreather face mask
Interventions: intervention 1: Oxygen
Intervention descriptions: intervention 1: Persons will undergo MRI, EEG, and complete computerized cognitive testing in baseline room air. Persons will then breathe 100% pure oxygen and undergo MRI, EEG, and complete computerized cognitive testing. Persons will serve as their own controls.

Protocol documents:
Prot_SAP_000.pdf: 
PROTOCOL: Neuroimaging During Pure Oxygen Breathing 
  
 
 
 
 
 
 
 
 
Study Title: Neuroimaging During Pure Oxygen Breathing 
 
NCT number: NCT03268590 
 
IRB Approval Date: March 6, 2018 
 
 
 


PROTOCOL: Neuroimaging During Pure Oxygen Breathing 
  
 
 
Consented study participants will be asked to come to the Case Western Reserve University Magnetic 
Resonance (MR) Facility located within University Hospitals on 11100 Euclid Ave, Cleveland OH 44106 at 
a scheduled date/time. Data collection will involve 1 visit lasting approximately 3-4 hours in length. 
 
 
PROCEDURE: 
1. Confirmation of signed informed consent & repeat MRI screening to ensure subject safety 
2. Obtain focused neurological history and physical examination 
3. Obtain baseline vital signs 
4. Apply HD-EEG head cap on scalp, apply EEG gel, and program EEG acquisition software, check 
impedances 
5. Obtain 5 minutes of baseline EEG recording 
6. While the participant is breathing room air and EEG is being recorded, administer baseline 
neurocognitive assessments 
7. Obtain baseline arterial blood sample for blood gas and venous blood sample for inflammatory 
markers. Perform Allen test for collateral circulation prior to obtaining arterial blood sample. 
Apply pressure over the artery for 5-10 minutes after the blood sample is obtained to minimize 
bleeding 
8. Obtain baseline exhaled breath sample 
9. Transfer participant to MRI scanning room. Final MRI safety check 
10. Apply MRI-compatible respiratory monitoring sensors, pulse oximeter probe, nasal cannula, face 
mask 
11. While the participant is breathing room air, MRI scan and simultaneous EEG recording begins 
12. Continuously monitor heart and respiratory rate, oxygenation during scanning session 
13. After baseline MR scans are acquired, scanning and EEG recording continues and oxygen 
administration is begun 
14. Following 30 minutes of 100% oxygen administration, MRI scan ends. Arterial blood gas sample 
and exhaled breath sample are obtained while oxygen administration and EEG recording 
continues. Perform Allen test for collateral circulation prior to obtaining arterial blood sample. 
Apply pressure over the artery for 5-10 minutes after the blood sample is obtained to minimize 
bleeding 
15. While continuing 100% oxygen breathing and EEG recording, repeat neurocognitive assessments 
16. 100% oxygen breathing discontinued. Room air breathing begins 
17. The participant is observed and vital signs are assessed for 30 minutes during room air breathing 
Arterial puncture site is assessed for hemostasis. Participant is assisted to remove EEG gel 
18. Participant is contacted within 1 week to assess for development of any adverse events 


STATISTICAL ANALYSIS PLAN: 
 
 
General statistical approaches: Sample size estimation and power analyses were based on a minimum 
statistical power of ≥ 0.80 at a two-tailed significance of 0.05. Physiologic measures were continuous in 
nature and frequency analyses with normality plots providing information of data distributions. 
Descriptive statistics include the mean, standard error of the mean (SEM), and range. Independent 
samples t-tests were utilized to compare males and females, incorporating the Levene test for 
homogeneity of variance. Paired t-tests were used to compare physiologic measures in 21% FiO2 versus 
100% FiO2.