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Neuroimaging During Pure Oxygen Breathing

Primary Purpose

Hyperoxia, Hypoxia, Brain, Neurobehavioral Manifestations

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Oxygen
Sponsored by
Case Western Reserve University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Hyperoxia focused on measuring Hyperoxia, Hypoxia, Brain

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Case Western Reserve University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All Study Participants

Arm Description

Breathing 21% oxygen via non-rebreather face mask followed by breathing 100% oxygen via non-rebreather face mask

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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).
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.

Full Information

First Posted
August 25, 2017
Last Updated
October 25, 2019
Sponsor
Case Western Reserve University
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1. Study Identification

Unique Protocol Identification Number
NCT03268590
Brief Title
Neuroimaging During Pure Oxygen Breathing
Official Title
Hyperoxia: An Unrecognized Mechanism for Inducing "Hypoxia-Like" Symptoms
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
October 2, 2017 (Actual)
Primary Completion Date
May 2, 2018 (Actual)
Study Completion Date
May 9, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Case Western Reserve University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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: 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. Determine if changes that might occur in brain blood flow are also accompanied by changes in the brain's electrical activity (EEG). 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperoxia, Hypoxia, Brain, Neurobehavioral Manifestations
Keywords
Hyperoxia, Hypoxia, Brain

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
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
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
All Study Participants
Arm Type
Experimental
Arm Description
Breathing 21% oxygen via non-rebreather face mask followed by breathing 100% oxygen via non-rebreather face mask
Intervention Type
Drug
Intervention Name(s)
Oxygen
Intervention 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.
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Height 152.5-195.5 cm, weight 40-135 kg. Exclusion Criteria: 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. History of claustrophobia
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael J Decker, PhD
Organizational Affiliation
Case Western Reserve University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24891124
Citation
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.
Results Reference
background
PubMed Identifier
9299881
Citation
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.
Results Reference
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PubMed Identifier
9453694
Citation
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. doi: 10.1002/(SICI)1096-8644(199712)104:43.0.CO;2-P.
Results Reference
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PubMed Identifier
23486058
Citation
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.
Results Reference
background
PubMed Identifier
19506312
Citation
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. doi: 10.1093/ilar.50.3.248.
Results Reference
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PubMed Identifier
19807920
Citation
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.
Results Reference
background
PubMed Identifier
19816726
Citation
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.
Results Reference
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Neuroimaging During Pure Oxygen Breathing

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