<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03268590</url>
  </required_header>
  <id_info>
    <org_study_id>CON215044</org_study_id>
    <secondary_id>FA8650-12-D6280 TO0052</secondary_id>
    <nct_id>NCT03268590</nct_id>
  </id_info>
  <brief_title>Neuroimaging During Pure Oxygen Breathing</brief_title>
  <official_title>Hyperoxia: An Unrecognized Mechanism for Inducing &quot;Hypoxia-Like&quot; Symptoms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Case Western Reserve University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Case Western Reserve University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators will conduct a non-randomized clinical trial to examine the effect of pure&#xD;
      oxygen breathing on the brain. The study will compare cerebral blood flow, cortical&#xD;
      electrical activity, and cognitive performance in 32 persons during room air (21% oxygen)&#xD;
      breathing and pure oxygen (100% oxygen) breathing. Subjects will be used as their own&#xD;
      controls. The investigators aim to:&#xD;
&#xD;
        1. Determine whether breathing 100% oxygen changes blood flow through the brain. The&#xD;
           investigators will learn whether brain blood flow is increased, decreased or stays the&#xD;
           same.&#xD;
&#xD;
        2. Determine if changes that might occur in brain blood flow are also accompanied by&#xD;
           changes in the brain's electrical activity (EEG).&#xD;
&#xD;
        3. Learn whether changes in the speed at which the brain processes information (cognitive&#xD;
           function) accompany changes in brain blood flow and electrical activity that may be&#xD;
           seen.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators will conduct a crossover design clinical trial to compare the effect of&#xD;
      room air breathing (21% inspired oxygen) with pure oxygen breathing (100% inspired oxygen) on&#xD;
      brain blood flow and cortical electrical activity. The study involves a one-time data&#xD;
      collection taking place at University Hospitals Cleveland Medical Center on the Case Western&#xD;
      Reserve University campus in Cleveland, Ohio. The investigators will perform neuroimaging&#xD;
      (MRI) with electroencephalographic (EEG) cortical network mapping and cognitive assessments&#xD;
      in all participants during room air breathing and again while breathing 100% pure oxygen.&#xD;
      Oxygen will be delivered through a non-rebreather mask. Arterial blood partial pressure of&#xD;
      oxygen (PaO2) will be measured twice, from arterial blood samples drawn during breathing room&#xD;
      air prior to the MRI scan and again after 30 minutes of breathing 100% oxygen immediately&#xD;
      following neuroimaging. Thus, the investigators will be able to determine if breathing pure&#xD;
      oxygen may temporarily change brain blood flow and breathing, leading to changes in cognitive&#xD;
      status such as euphoria or slowed reflexes. Information gained in this study may have direct&#xD;
      operational relevance by helping us to understand one potential cause of &quot;Unexplained&#xD;
      Physiologic Events&quot; that are reported in some aircraft pilots when flying at high altitude.&#xD;
      Information gained could lead to development of new gas mixtures for use by personnel working&#xD;
      in low oxygen high altitude environments.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2, 2017</start_date>
  <completion_date type="Actual">May 9, 2018</completion_date>
  <primary_completion_date type="Actual">May 2, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <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</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cerebral Blood Flow</measure>
    <time_frame>Baseline and at 30 minutes</time_frame>
    <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).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cortical Network Activity</measure>
    <time_frame>Baseline and at 30 minutes</time_frame>
    <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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Performance</measure>
    <time_frame>Baseline and at 30 minutes</time_frame>
    <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.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Hyperoxia</condition>
  <condition>Hypoxia, Brain</condition>
  <condition>Neurobehavioral Manifestations</condition>
  <arm_group>
    <arm_group_label>All Study Participants</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Breathing 21% oxygen via non-rebreather face mask followed by breathing 100% oxygen via non-rebreather face mask</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxygen</intervention_name>
    <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.</description>
    <arm_group_label>All Study Participants</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Persons recruited from currently approved Human Subject Panel for high altitude&#xD;
             studies at Wright Patterson Air Force Base, Dayton, OH. Volunteers will have&#xD;
             documentation of past exposure to hypobaric conditions, either from past high-altitude&#xD;
             flight, as hypobaric chamber personnel, or as participants in previous/current high&#xD;
             altitude studies. Persons without past exposure to hypobaric conditions were also&#xD;
             eligible to participate.&#xD;
&#xD;
          2. Height 152.5-195.5 cm, weight 40-135 kg.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Persons who have contraindications to MRI such as cardiac pacemakers, intracranial&#xD;
             aneurysm clips, metallic implants or external clips within 10 mm of the head;&#xD;
             implanted metallic devices such as pumps or previously implanted neurostimulation&#xD;
             devices; cochlear implants, defibrillators, pacing wires, body piercings that cannot&#xD;
             be removed, metal filings such as shrapnel, tattoos on the head and neck, or medical&#xD;
             conditions contraindicated for MRI safety.&#xD;
&#xD;
          2. History of claustrophobia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael J Decker, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Case Western Reserve University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Case Western Reserve University</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <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.</citation>
    <PMID>24891124</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>9299881</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>9453694</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>23486058</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>19506312</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>19807920</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>19816726</PMID>
  </reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>August 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <results_first_submitted>July 30, 2019</results_first_submitted>
  <results_first_submitted_qc>October 25, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 13, 2019</results_first_posted>
  <last_update_submitted>October 25, 2019</last_update_submitted>
  <last_update_submitted_qc>October 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Case Western Reserve University</investigator_affiliation>
    <investigator_full_name>Michael J. Decker</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Hyperoxia</keyword>
  <keyword>Hypoxia, Brain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neurobehavioral Manifestations</mesh_term>
    <mesh_term>Hypoxia, Brain</mesh_term>
    <mesh_term>Hypoxia</mesh_term>
    <mesh_term>Hyperoxia</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 6, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/90/NCT03268590/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_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.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>All Study Participants</title>
          <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.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="32">One participant did not complete MRI due to a previously undiagnosed subdermal metal shard in scalp.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Previously unknown exclusion criteria</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>33 participants were studied; each served as their own control and received both 21% oxygen and 100% oxygen</population>
      <group_list>
        <group group_id="B1">
          <title>All Study Participants</title>
          <description>Breathing 21% and 100% oxygen via non-rebreather face mask&#xD;
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.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="33"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39.61" spread="13.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.68" spread="4.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cerebral Blood Flow</title>
        <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).</description>
        <time_frame>Baseline and at 30 minutes</time_frame>
        <population>Participants with usable MRI arterial spin labeling (ASL) data</population>
        <group_list>
          <group group_id="O1">
            <title>All Study Participants</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Cerebral Blood Flow</title>
          <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).</description>
          <population>Participants with usable MRI arterial spin labeling (ASL) data</population>
          <units>ml/min/100g tissue</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>21% oxygen cerebral perfusion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.54" spread="12.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>100% oxygen cerebral perfusion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.17" spread="11.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cortical Network Activity</title>
        <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).</description>
        <time_frame>Baseline and at 30 minutes</time_frame>
        <population>Participants with usable MRI ASL (arterial spin labeling) data</population>
        <group_list>
          <group group_id="O1">
            <title>All Study Participants</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Cortical Network Activity</title>
          <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).</description>
          <population>Participants with usable MRI ASL (arterial spin labeling) data</population>
          <units>microvolt/second</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>21% oxygen spectral power temporal alpha activity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.15" spread="0.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>100% oxygen spectral power temporal alpha activity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.75" spread="0.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Performance</title>
        <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.</description>
        <time_frame>Baseline and at 30 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Study Participants</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Performance</title>
          <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.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>21% oxygen cognitive assessment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.91" spread="2.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>100% oxygen cognitive assessment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="221.70" spread="2.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>7 days</time_frame>
      <desc>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.</desc>
      <group_list>
        <group group_id="E1">
          <title>All Study Participants When Breathing Room Air</title>
          <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.</description>
        </group>
        <group group_id="E2">
          <title>All Study Participants When Breathing Pure Oxygen</title>
          <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.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>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.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Michael John Decker, PhD</name_or_title>
      <organization>Case Western Reserve University</organization>
      <phone>216-368-2467</phone>
      <email>mjd6@case.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03268590
org study id: CON215044
secondary id: FA8650-12-D6280 TO0052
nct id: NCT03268590
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
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 mask
primary purpose: Basic Science
masking: None (Open Label)
measure: Cerebral Blood Flow
time frame: Baseline and at 30 minutes
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).
measure: Cortical Network Activity
time frame: Baseline and at 30 minutes
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).
measure: Cognitive Performance
time frame: Baseline and at 30 minutes
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.
arm group label: All Study Participants
arm group type: Experimental
description: Breathing 21% oxygen via non-rebreather face mask followed by breathing 100% oxygen via non-rebreather face mask
intervention type: Drug
intervention name: Oxygen
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.
arm group label: All Study Participants
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Michael J Decker, PhD
role: Principal Investigator
affiliation: Case Western Reserve University
facility: 
country: United States
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.
PMID: 24891124
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.
PMID: 9299881
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.
PMID: 9453694
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.
PMID: 23486058
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.
PMID: 19506312
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.
PMID: 19807920
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.
PMID: 19816726
responsible party type: Principal Investigator
investigator affiliation: Case Western Reserve University
investigator full name: Michael J. Decker
investigator title: Associate Professor
mesh term: Neurobehavioral Manifestations
mesh term: Hypoxia, Brain
mesh term: Hypoxia
mesh term: Hyperoxia
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 