Hyperoxia, Hypoxia, Brain, Neurobehavioral Manifestations
Conditions
Keywords
Hyperoxia, Hypoxia, Brain
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.
Interventions
DRUGOxygen
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.
Sponsors
Case Western Reserve University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
All participants will undergo neuroimaging (MRI) with electroencephalographic (EEG) cortical network mapping and cognitive assessments during room air breathing (placebo). Room air (21% inspired oxygen) will be delivered via non-rebreather face mask. Persons will serve as their own control and will next undergo neuroimaging (MRI) with electroencephalographic (EEG) cortical network mapping and cognitive assessments during pure oxygen breathing. Pure oxygen (100% inspired oxygen) will be delivered via non-rebreather face mask
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Persons recruited from currently approved Human Subject Panel for high altitude studies at Wright Patterson Air Force Base, Dayton, OH. Volunteers will have documentation of past exposure to hypobaric conditions, either from past high-altitude flight, as hypobaric chamber personnel, or as participants in previous/current high altitude studies. Persons without past exposure to hypobaric conditions were also eligible to participate. 2. Height 152.5-195.5 cm, weight 40-135 kg.
Exclusion criteria
1. Persons who have contraindications to MRI such as cardiac pacemakers, intracranial aneurysm clips, metallic implants or external clips within 10 mm of the head; implanted metallic devices such as pumps or previously implanted neurostimulation devices; cochlear implants, defibrillators, pacing wires, body piercings that cannot be removed, metal filings such as shrapnel, tattoos on the head and neck, or medical conditions contraindicated for MRI safety. 2. History of claustrophobia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral Blood Flow | Baseline and at 30 minutes | Change in brain blood flow from Baseline Room Air breathing (21% inspired oxygen) to Pure Oxygen breathing (100% inspired oxygen). Measured using Magnetic Resonance Imaging (MRI). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cortical Network Activity | Baseline and at 30 minutes | Change in alpha cortical electrical activity in the temporal brain region from Baseline Room Air breathing (21% inspired oxygen) to Pure Oxygen breathing (100% inspired oxygen). Measured using MRI-compatible 64-electrode high-density electroencephalography (EEG). |
| Cognitive Performance | Baseline and at 30 minutes | Change in cognitive performance from Baseline Room Air breathing (21% inspired oxygen) to Pure Oxygen breathing (100% inspired oxygen). Measured using the General Cognitive Function score on the MicroCog\^TM Assessment of Cognitive Functioning (TM= trademark of Pearson Education, Inc., New York, NY). The computer-administered MicroCog measures changes in cognitive performance in 9 domains related to attention, memory, reasoning, spatial processing, and reaction time. The General Cognitive Function score is a summed score and measures accuracy and speed processing. Education-adjusted Standardized Scores used to compare each study participant against population norms. Higher scores are indicative of better performance. Index Standardized Scores of 69 and below are considered Below Average; scores of 70-84 are considered Low Average; scores of 85-114 are considered to be Average; and scores of 115 and above are considered to be Above Average. |
Countries
United States
Participant flow
Recruitment details
41 persons responded to study advertisements and were screened for eligibility between September 2017 and April 2018. 33 were studied.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Breathing 21% and 100% oxygen via non-rebreather face mask
Oxygen: Persons will undergo MRI, EEG, and complete computerized cognitive testing in baseline room air. Persons will next breathe 100% pure oxygen and undergo MRI, EEG, and complete computerized cognitive testing. Persons will serve as their own controls. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Previously unknown exclusion criteria | 1 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 39.61 years STANDARD_DEVIATION 13.8 |
| BMI | 26.68 kg/m^2 STANDARD_DEVIATION 4.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Region of Enrollment United States | 33 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 33 |
| other Total, other adverse events | 0 / 33 | 0 / 33 |
| serious Total, serious adverse events | 0 / 33 | 0 / 33 |
Outcome results
Primary
Cerebral Blood Flow
Change in brain blood flow from Baseline Room Air breathing (21% inspired oxygen) to Pure Oxygen breathing (100% inspired oxygen). Measured using Magnetic Resonance Imaging (MRI).
Time frame: Baseline and at 30 minutes
Population: Participants with usable MRI arterial spin labeling (ASL) data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Study Participants | Cerebral Blood Flow | 21% oxygen cerebral perfusion | 48.54 ml/min/100g tissue | Standard Deviation 12.78 |
| All Study Participants | Cerebral Blood Flow | 100% oxygen cerebral perfusion | 36.17 ml/min/100g tissue | Standard Deviation 11.97 |
p-value: <0.05t-test, 2 sided
Secondary
Cognitive Performance
Change in cognitive performance from Baseline Room Air breathing (21% inspired oxygen) to Pure Oxygen breathing (100% inspired oxygen). Measured using the General Cognitive Function score on the MicroCog\^TM Assessment of Cognitive Functioning (TM= trademark of Pearson Education, Inc., New York, NY). The computer-administered MicroCog measures changes in cognitive performance in 9 domains related to attention, memory, reasoning, spatial processing, and reaction time. The General Cognitive Function score is a summed score and measures accuracy and speed processing. Education-adjusted Standardized Scores used to compare each study participant against population norms. Higher scores are indicative of better performance. Index Standardized Scores of 69 and below are considered Below Average; scores of 70-84 are considered Low Average; scores of 85-114 are considered to be Average; and scores of 115 and above are considered to be Above Average.
Time frame: Baseline and at 30 minutes
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Study Participants | Cognitive Performance | 21% oxygen cognitive assessment | 97.91 score on a scale | Standard Error 2.22 |
| All Study Participants | Cognitive Performance | 100% oxygen cognitive assessment | 221.70 score on a scale | Standard Error 2.49 |
p-value: <0.05t-test, 2 sided
Secondary
Cortical Network Activity
Change in alpha cortical electrical activity in the temporal brain region from Baseline Room Air breathing (21% inspired oxygen) to Pure Oxygen breathing (100% inspired oxygen). Measured using MRI-compatible 64-electrode high-density electroencephalography (EEG).
Time frame: Baseline and at 30 minutes
Population: Participants with usable MRI ASL (arterial spin labeling) data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Study Participants | Cortical Network Activity | 21% oxygen spectral power temporal alpha activity | 6.15 microvolt/second | Standard Error 0.34 |
| All Study Participants | Cortical Network Activity | 100% oxygen spectral power temporal alpha activity | 6.75 microvolt/second | Standard Error 0.45 |
p-value: <0.05t-test, 2 sided