<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/NCT03023449</url>
  </required_header>
  <id_info>
    <org_study_id>824559</org_study_id>
    <nct_id>NCT03023449</nct_id>
  </id_info>
  <brief_title>Diffuse Optical Monitoring With Inhaled Nitric Oxide</brief_title>
  <acronym>DOMINO</acronym>
  <official_title>Diffuse Optical Monitoring With Inhaled Nitric Oxide</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Steven Messe</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Mallinckrodt</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>No</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>
      This study is a non-randomized, Phase 2 clinical trial designed to measure the cerebral blood&#xD;
      flow (CBF) response to inhaled nitric oxide in acute ischemic stroke patients and healthy&#xD;
      subjects. The monitoring is a 35 minute session during which cerebral hemodynamics will be&#xD;
      monitored with both diffuse correlation spectroscopy (DCS) and transcranial doppler&#xD;
      ultrasonography (TCD) while blood pressure, heart rate, cardiac output, respiratory rate, end&#xD;
      oxygen saturation, and inhaled nitric oxide (NO)/nitrogen dioxide (NO2) concentration, are&#xD;
      continuously monitored.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 4, 2017</start_date>
  <completion_date type="Anticipated">July 2023</completion_date>
  <primary_completion_date type="Anticipated">July 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in cerebral blood flow during the administration of iNO</measure>
    <time_frame>Conclusion of the 35 minute protocol</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in blood flow velocity as measured by TCD during iNO administration</measure>
    <time_frame>Conclusion of the 35 minute protocol</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in mean arterial blood pressure (MAP) during iNO administration</measure>
    <time_frame>Conclusion of the 35 minute protocol</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum CBF effect after the introduction of iNO</measure>
    <time_frame>Conclusion of the 35 minute protocol</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of residual effect after cessation of iNO (time to return to baseline)</measure>
    <time_frame>Conclusion of the 35 minute protocol</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Stroke</condition>
  <arm_group>
    <arm_group_label>Healthy Controls</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The protocol will be a 35-minute monitoring session, during which cerebral hemodynamics will be monitored with both DCS and TCD, while blood pressure, heart rate, cardiac output, respiratory rate, end oxygen saturation, and inhaled nitric oxide concentration, are continuously monitored. 5 minutes of baseline hemodynamics will be assessed, after which the subject will breath iNO for 5 minutes, followed by 5 minutes of room air. This iNO/room air cycle will be repeated with a total of 3 different iNO concentrations. The full protocol will require 35 minutes. Subjects will be called at 24 hours after the monitoring session to determine any tolerability issues or adverse events.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Acute Ischemic Stroke</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be enrolled in the study within 72 hours of stroke symptom onset. The protocol will be a 35-minute monitoring session, during which cerebral hemodynamics will be monitored with both DCS and TCD, while blood pressure, heart rate, cardiac output, respiratory rate, end oxygen saturation, and inhaled nitric oxide concentration, are continuously monitored. 5 minutes of baseline hemodynamics will be assessed, after which the subject will breath iNO for 5 minutes, followed by 5 minutes of room air. This iNO/room air cycle will be repeated with a total of 3 different iNO concentrations. The full protocol will require 35 minutes. Subjects will be undergo a final assessment at 24 hours after the monitoring session to determine any tolerability issues or adverse events.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nitric Oxide</intervention_name>
    <description>Inhaled Nitric Oxide gas</description>
    <arm_group_label>Acute Ischemic Stroke</arm_group_label>
    <arm_group_label>Healthy Controls</arm_group_label>
    <other_name>iNO</other_name>
    <other_name>NO2</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Stroke Patients:&#xD;
&#xD;
          1. Age greater than 18&#xD;
&#xD;
          2. Acute ischemic stroke in the territory of the anterior, middle, or posterior cerebral&#xD;
             artery, on either side of the brain&#xD;
&#xD;
          3. Study can be initiated within 72 hours of stroke symptom onset&#xD;
&#xD;
        3. Ability and willingness to sign informed consent&#xD;
&#xD;
        Healthy subjects:&#xD;
&#xD;
          1. Age greater than 18&#xD;
&#xD;
          2. Ability and willingness to sign informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Stroke subjects:&#xD;
&#xD;
          1. History of prior stroke or transient ischemic attack&#xD;
&#xD;
          2. Known cerebrovascular abnormality&#xD;
&#xD;
          3. History of congestive heart failure&#xD;
&#xD;
          4. Presence of pneumonia or active pulmonary infection&#xD;
&#xD;
          5. Current use of any NO donor medication (sodium nitroprusside or nitroglycerin)&#xD;
&#xD;
          6. Age less than 18 years&#xD;
&#xD;
          7. Skull defect that would interfere with CBF monitoring&#xD;
&#xD;
          8. Pregnancy&#xD;
&#xD;
          9. Structural brain lesion&#xD;
&#xD;
         10. Prior neurosurgical procedure&#xD;
&#xD;
         11. History of psychiatric disease&#xD;
&#xD;
         12. Any medical condition that the clinical investigator feels would pose a hazard to the&#xD;
             subject if he/she participated in the study&#xD;
&#xD;
        Healthy subjects:&#xD;
&#xD;
          1. History of any neurological disease&#xD;
&#xD;
          2. History of stroke or transient ischemic attack&#xD;
&#xD;
          3. Known cerebrovascular abnormality&#xD;
&#xD;
          4. History of congestive heart failure&#xD;
&#xD;
          5. History of chronic pulmonary disease such as asthma or chronic obstructive pulmonary&#xD;
             disease&#xD;
&#xD;
          6. Presence of pneumonia or active pulmonary infection&#xD;
&#xD;
          7. Current use of any NO donor medication (sodium nitroprusside or nitroglycerin)&#xD;
&#xD;
          8. Age less than 18 years&#xD;
&#xD;
          9. Skull defect that would interfere with CBF monitoring&#xD;
&#xD;
         10. Pregnancy (urine or blood tests will not be performed)&#xD;
&#xD;
         11. Structural brain lesion&#xD;
&#xD;
         12. Prior neurosurgical procedure&#xD;
&#xD;
         13. History of psychiatric disease&#xD;
&#xD;
         14. Any medical condition that the clinical investigator feels would pose a hazard to the&#xD;
             subject if he/she participated in the study&#xD;
&#xD;
         15. Cognitive impairment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven R Messe, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital of the University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>January 13, 2017</study_first_submitted>
  <study_first_submitted_qc>January 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>November 23, 2022</last_update_submitted>
  <last_update_submitted_qc>November 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pennsylvania</investigator_affiliation>
    <investigator_full_name>Steven Messe</investigator_full_name>
    <investigator_title>Associate Professor of Neurology</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nitric Oxide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03023449
org study id: 824559
nct id: NCT03023449
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is a non-randomized, Phase 2 clinical trial designed to measure the cerebral blood
      flow (CBF) response to inhaled nitric oxide in acute ischemic stroke patients and healthy
      subjects. The monitoring is a 35 minute session during which cerebral hemodynamics will be
      monitored with both diffuse correlation spectroscopy (DCS) and transcranial doppler
      ultrasonography (TCD) while blood pressure, heart rate, cardiac output, respiratory rate, end
      oxygen saturation, and inhaled nitric oxide (NO)/nitrogen dioxide (NO2) concentration, are
      continuously monitored.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change in cerebral blood flow during the administration of iNO
time frame: Conclusion of the 35 minute protocol
measure: Change in blood flow velocity as measured by TCD during iNO administration
time frame: Conclusion of the 35 minute protocol
measure: Change in mean arterial blood pressure (MAP) during iNO administration
time frame: Conclusion of the 35 minute protocol
measure: Time to maximum CBF effect after the introduction of iNO
time frame: Conclusion of the 35 minute protocol
measure: Duration of residual effect after cessation of iNO (time to return to baseline)
time frame: Conclusion of the 35 minute protocol
arm group label: Healthy Controls
arm group type: Experimental
description: The protocol will be a 35-minute monitoring session, during which cerebral hemodynamics will be monitored with both DCS and TCD, while blood pressure, heart rate, cardiac output, respiratory rate, end oxygen saturation, and inhaled nitric oxide concentration, are continuously monitored. 5 minutes of baseline hemodynamics will be assessed, after which the subject will breath iNO for 5 minutes, followed by 5 minutes of room air. This iNO/room air cycle will be repeated with a total of 3 different iNO concentrations. The full protocol will require 35 minutes. Subjects will be called at 24 hours after the monitoring session to determine any tolerability issues or adverse events.
arm group label: Acute Ischemic Stroke
arm group type: Experimental
description: Patients will be enrolled in the study within 72 hours of stroke symptom onset. The protocol will be a 35-minute monitoring session, during which cerebral hemodynamics will be monitored with both DCS and TCD, while blood pressure, heart rate, cardiac output, respiratory rate, end oxygen saturation, and inhaled nitric oxide concentration, are continuously monitored. 5 minutes of baseline hemodynamics will be assessed, after which the subject will breath iNO for 5 minutes, followed by 5 minutes of room air. This iNO/room air cycle will be repeated with a total of 3 different iNO concentrations. The full protocol will require 35 minutes. Subjects will be undergo a final assessment at 24 hours after the monitoring session to determine any tolerability issues or adverse events.
intervention type: Drug
intervention name: Nitric Oxide
description: Inhaled Nitric Oxide gas
arm group label: Acute Ischemic Stroke
arm group label: Healthy Controls
other name: iNO
other name: NO2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Steven R Messe, M.D.
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pennsylvania
investigator full name: Steven Messe
investigator title: Associate Professor of Neurology
mesh term: Nitric Oxide
sharing ipd: No