Neuroimaging During Pure Oxygen Breathing

• Sponsor: Case Western Reserve University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03268590
• Collaborator: (none)
• Enrollment: 33
• Location: 1
• Arm: 1
• Actual Duration (Months): 7.2
• Patients Per Site Per Month: 4.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hyperoxia; Hypoxia, Brain; Neurobehavioral Manifestations	Drug: Oxygen	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• 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 maskAll 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
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Hyperoxia: An Unrecognized Mechanism for Inducing "Hypoxia-Like" Symptoms
• Actual Study Start Date: Oct 2, 2017
• Actual Primary Completion Date: May 2, 2018
• Actual Study Completion Date: May 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: All Study Participants Breathing 21% oxygen via non-rebreather face mask followed by breathing 100% oxygen via non-rebreather face mask	Drug: Oxygen; 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Case Western Reserve University	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• Case Western Reserve University

Investigators

• Principal Investigator: Michael J Decker, PhD, Case Western Reserve University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 6, 2019

More Information

Publications

• Baekey DM, Feng P, Decker MJ, Strohl KP. Breathing and sleep: measurement methods, genetic influences, and developmental impacts. ILAR J. 2009;50(3):248-61. Review.
• Beall CM, Strohl KP, Blangero J, Williams-Blangero S, Almasy LA, Decker MJ, Worthman CM, Goldstein MC, Vargas E, Villena M, Soria R, Alarcon AM, Gonzales C. Ventilation and hypoxic ventilatory response of Tibetan and Aymara high altitude natives. Am J Phys Anthropol. 1997 Dec;104(4):427-47.
• Beall CM, Strohl KP, Blangero J, Williams-Blangero S, Decker MJ, Brittenham GM, Goldstein MC. Quantitative genetic analysis of arterial oxygen saturation in Tibetan highlanders. Hum Biol. 1997 Oct;69(5):597-604.
• Decker MJ, Eyal S, Shinar Z, Fuxman Y, Cahan C, Reeves WC, Baharav A. Validation of ECG-derived sleep architecture and ventilation in sleep apnea and chronic fatigue syndrome. Sleep Breath. 2010 Sep;14(3):233-9. doi: 10.1007/s11325-009-0305-z. Epub 2009 Oct 9.
• Decker MJ, Tabassum H, Lin JM, Reeves WC. Electroencephalographic correlates of Chronic Fatigue Syndrome. Behav Brain Funct. 2009 Oct 6;5:43. doi: 10.1186/1744-9081-5-43.
• Gao Y, Goodnough CL, Erokwu BO, Farr GW, Darrah R, Lu L, Dell KM, Yu X, Flask CA. Arterial spin labeling-fast imaging with steady-state free precession (ASL-FISP): a rapid and quantitative perfusion technique for high-field MRI. NMR Biomed. 2014 Aug;27(8):996-1004. doi: 10.1002/nbm.3143. Epub 2014 Jun 3.
• Ma D, Gulani V, Seiberlich N, Liu K, Sunshine JL, Duerk JL, Griswold MA. Magnetic resonance fingerprinting. Nature. 2013 Mar 14;495(7440):187-92. doi: 10.1038/nature11971.

• Responsible Party: Michael J. Decker, Associate Professor, Case Western Reserve University
• ClinicalTrials.gov Identifier: NCT03268590
• Other Study ID Numbers: CON215044; FA8650-12-D6280 TO0052
• First Posted: Aug 31, 2017
• Last Update Posted: Nov 13, 2019
• Last Verified: Oct 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Michael J. Decker, Associate Professor, Case Western Reserve University: Hyperoxia; Hypoxia, Brain
• Additional relevant MeSH terms: Neurobehavioral Manifestations; Hypoxia, Brain; Hypoxia; Hyperoxia

Study Results

Participant Flow

Recruitment Details	41 persons responded to study advertisements and were screened for eligibility between September 2017 and April 2018. 33 were studied.

Arm/Group Title	All Study Participants
Arm/Group Description	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.
Period Title: Overall Study
STARTED	33
COMPLETED	32
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	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.
Overall Participants	33
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.61 (13.80)
Sex: Female, Male (Count of Participants)
Female	14 42.4%
Male	19 57.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.1%
Not Hispanic or Latino	31 93.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3%
White	30 90.9%
More than one race	0 0%
Unknown or Not Reported	2 6.1%
Region of Enrollment (participants) [Number]
United States	33 100%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.68 (4.15)

Outcome Measures

1. Primary Outcome

Title	Cerebral Blood Flow
Description	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

Outcome Measure Data

Analysis Population Description

Participants with usable MRI arterial spin labeling (ASL) data

Arm/Group Title	All Study Participants
Arm/Group Description	All 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.
Measure Participants	30
21% oxygen cerebral perfusion	48.54 (12.78)
100% oxygen cerebral perfusion	36.17 (11.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Study Participants
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Cortical Network Activity
Description	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

Outcome Measure Data

Analysis Population Description

Participants with usable MRI ASL (arterial spin labeling) data

Arm/Group Title	All Study Participants
Arm/Group Description	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.
Measure Participants	30
21% oxygen spectral power temporal alpha activity	6.15 (0.34)
100% oxygen spectral power temporal alpha activity	6.75 (0.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Study Participants
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Cognitive Performance
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Study Participants
Arm/Group Description	All 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.
Measure Participants	30
21% oxygen cognitive assessment	97.91 (2.22)
100% oxygen cognitive assessment	221.70 (2.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Study Participants
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	7 days
Adverse Event Reporting Description	The participants were healthy and received 100% oxygen. Oxygen is routinely used by healthy persons engaged in certain occupations such as firefighters and high altitude aviators and its use is not considered to be a contributor to all-cause mortality.
Arm/Group Title	All Study Participants When Breathing Room Air		All Study Participants When Breathing Pure Oxygen
Arm/Group Description	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.		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.
All Cause Mortality
	All Study Participants When Breathing Room Air		All Study Participants When Breathing Pure Oxygen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/33 (0%)
Serious Adverse Events
	All Study Participants When Breathing Room Air		All Study Participants When Breathing Pure Oxygen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	All Study Participants When Breathing Room Air		All Study Participants When Breathing Pure Oxygen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/33 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Funding source is the United States Air Force Research Laboratories. The AFRL must approve any presentation or publication of the study results before they can be disseminated.