<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/NCT04435834</url>
  </required_header>
  <id_info>
    <org_study_id>CHLA-20-00136</org_study_id>
    <nct_id>NCT04435834</nct_id>
  </id_info>
  <brief_title>Individual Cerebral Hemodynamic Oxygenation Relationships</brief_title>
  <acronym>ICHOR</acronym>
  <official_title>Individual Cerebral Hemodynamic Oxygenation Relationships</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital Los Angeles</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized controlled trial in patients who require clinical anesthesia. The main&#xD;
      purpose of this study is to understand whether there are differences in the cerebral blood&#xD;
      flow, and oxygen metabolism affected by two types of anesthesia: propofol or sevoflurane.&#xD;
      Subjects who require clinical anesthesia for a clinical MRI and for whom the use of propofol&#xD;
      and sevoflurane are in clinical equipoise will be offered to have the anesthesia they will&#xD;
      receive during their MRI randomized. All eligible subjects will be asked to provide informed&#xD;
      consent before participating in the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized controlled trial in patients who require clinical anesthesia. The main&#xD;
      purpose of this study is to understand whether there are differences in the cerebral blood&#xD;
      flow, and oxygen metabolism affected by two types of anesthesia: propofol or sevoflurane.&#xD;
      Subjects who require clinical anesthesia for a clinical MRI and for whom the use of propofol&#xD;
      and sevoflurane are in clinical equipoise will be offered to have the anesthesia they will&#xD;
      receive during their MRI randomized. All eligible subjects will be asked to provide informed&#xD;
      consent before participating in the study.&#xD;
&#xD;
      Treatment:&#xD;
&#xD;
      All patients will be screened to ensure propofol and sevoflurane are in clinical equipoise.&#xD;
      Those who meet eligibility criteria, and who undergo the informed consent, will be randomize&#xD;
      to receive propofol or sevoflurane during their MRI. Standard-of-care anesthesia safety, dose&#xD;
      and monitoring will not be changed. During their MRI, additional images will be acquired that&#xD;
      measure the cerebral blood flow and cerebral venous oxygenation. These additional images will&#xD;
      take up-to 10 extra minutes to acquire. This will increase the duration each subject spends&#xD;
      under anesthesia, and in the MRI scanner by up-to a total of 10 extra minutes.&#xD;
&#xD;
      Safety Assessment:&#xD;
&#xD;
      To ensure that either propofol or sevoflurane are in clinical equipoise, all patients will be&#xD;
      screened by an anesthesiologist. The experiment will occur in the standard-of-care clinical&#xD;
      MRI environment. All patient safety and monitoring will remain in place. Throughout the&#xD;
      induction, maintenance and recovery from anesthesia, all procedures will occur in the&#xD;
      standard of care environment and will be overseen by trained clinical personnel.&#xD;
&#xD;
      Efficacy Assessment:&#xD;
&#xD;
      Cerebral blood flow and metabolism MRIs will be collected from all subjects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 9, 2020</start_date>
  <completion_date type="Anticipated">September 10, 2026</completion_date>
  <primary_completion_date type="Anticipated">September 10, 2026</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Subjects will be randomized in a stratified, blocked study design. Stratification is based on two factors: gestational age (2 groups: ≥37 weeks and ≤37 weeks) and postmenstrual age at MRI (2 groups: ≥37 weeks and ≤37 weeks). Blocking of each stratum is performed in groups of 4.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
    <masking_description>Participant and care provider will be aware randomization status. Investigator and outcomes assessor will be masked.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in cerebral blood flow (ml blood/100g/min)</measure>
    <time_frame>Time points over which the change is assessed: change from (1) start of MRI, through (2) MRI completion, an average of 60 minutes.</time_frame>
    <description>Phase contrast (PC) acquisition via MRI will be used to assess any impact of anesthesia on cerebral blood flow.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in cerebral metabolic rate of oxygen (ml O2/100g/min)</measure>
    <time_frame>Time points over which the change is assessed: change from (1) start of MRI, through (2) MRI completion, an average of 60 minutes.</time_frame>
    <description>T2 relaxation under spin tagging (TRUST) acquisition via MRI will be used to assess any impact of anesthesia on cerebral metabolic rate of oxygen.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Anesthesia</condition>
  <condition>Anesthesia; Reaction</condition>
  <arm_group>
    <arm_group_label>Randomized propofol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subject will receive propofol anesthesia during their MRI. Dosage form: injectable solution. Dosage: 100-300 mcg/kg/min, or as per clinical standard of care appropriate for specific subjects.&#xD;
Frequency and duration: continuous infusion while undergoing MRI.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Randomized sevoflurane</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subject will receive sevoflurane anesthesia during their MRI. Dosage form: volatile liquid for inhalation Dosing: 0-1 month full term neonate (3.3% in oxygen), 1-6 months old (3% in oxygen), 6 months to &lt;3 years old (2.8% in oxygen), or as per clinical standard of care appropriate for specific subjects.&#xD;
Frequency and duration: continuous infusion while undergoing MRI.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol or Sevoflurane</intervention_name>
    <description>Patient's will be randomized to the group receiving propofol, or the group receiving sevoflurane.</description>
    <arm_group_label>Randomized propofol</arm_group_label>
    <arm_group_label>Randomized sevoflurane</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who are scheduled for a clinically indicated MRI at the sponsor institution.&#xD;
&#xD;
          -  Patients who are able to tolerate an MRI.&#xD;
&#xD;
          -  Patients who require clinical anesthesia for their MRI.&#xD;
&#xD;
          -  Patients with conditions not believed to alter oxygen metabolism or blood flow in the&#xD;
             brain, including but not limited to patients with orthopedic indications, undescended&#xD;
             testicles, hernia repairs, term equivalent age scans.&#xD;
&#xD;
          -  Patients who have no medical conditions that make the use of propofol or sevoflurane&#xD;
             better for their clinical outcome.&#xD;
&#xD;
          -  Patients between birth and up-to 1 year of age.&#xD;
&#xD;
          -  Patients with conditions known to alter oxygen metabolism or blood flow in the brain,&#xD;
             e.g. traumatic brain injury, hypoxic ischemic encephalopathy, tumor.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with an MRI-incompatible device or implant (e.g. pacemakers, stents)&#xD;
&#xD;
          -  Preterm infants less than 25 weeks postmenstrual age (PMA) at the time of the scan.&#xD;
&#xD;
          -  Patients who are clinically too unstable to extend their MRI by up-to 10 minutes.&#xD;
&#xD;
          -  Patients who do not require clinical anesthesia.&#xD;
&#xD;
          -  Patients at risk for propofol infusion syndrome (known severe metabolic acidosis,&#xD;
             hyperkalemia, lipemia, rhabdomyolysis, hepatomegaly, renal failure, ECG ST segment&#xD;
             elevation, and/or cardiac failure)&#xD;
&#xD;
          -  Patients at risk for sevoflurane-based malignant hyperthermia (known ryanodine&#xD;
             receptor mutations)&#xD;
&#xD;
          -  Patient at risk for sensitivity to volatile halogenated anesthetic agents (known&#xD;
             congenital Long QT Syndrome or patients taking drugs that can prolong the QT&#xD;
             interval),&#xD;
&#xD;
          -  Patients with Perioperative Hyperkalemia (known neuromuscular disease, particularly&#xD;
             Duchenne muscular dystrophy)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>1 Year</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Matthew Borzage, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Los Angeles</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hannah Wiseman</last_name>
    <phone>323-361-3963</phone>
    <email>hwiseman@chla.usc.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Candice Mulder</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>July 24, 2023</last_update_submitted>
  <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Magnetic Resonance Imaging</keyword>
  <keyword>Cerebral Blood Flow</keyword>
  <keyword>Cerebral Metabolism</keyword>
  <keyword>Anesthesia</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Propofol</mesh_term>
    <mesh_term>Sevoflurane</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/NCT04435834
org study id: CHLA-20-00136
nct id: NCT04435834
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a randomized controlled trial in patients who require clinical anesthesia. The main
      purpose of this study is to understand whether there are differences in the cerebral blood
      flow, and oxygen metabolism affected by two types of anesthesia: propofol or sevoflurane.
      Subjects who require clinical anesthesia for a clinical MRI and for whom the use of propofol
      and sevoflurane are in clinical equipoise will be offered to have the anesthesia they will
      receive during their MRI randomized. All eligible subjects will be asked to provide informed
      consent before participating in the study.
This is a randomized controlled trial in patients who require clinical anesthesia. The main
      purpose of this study is to understand whether there are differences in the cerebral blood
      flow, and oxygen metabolism affected by two types of anesthesia: propofol or sevoflurane.
      Subjects who require clinical anesthesia for a clinical MRI and for whom the use of propofol
      and sevoflurane are in clinical equipoise will be offered to have the anesthesia they will
      receive during their MRI randomized. All eligible subjects will be asked to provide informed
      consent before participating in the study.

      Treatment:

      All patients will be screened to ensure propofol and sevoflurane are in clinical equipoise.
      Those who meet eligibility criteria, and who undergo the informed consent, will be randomize
      to receive propofol or sevoflurane during their MRI. Standard-of-care anesthesia safety, dose
      and monitoring will not be changed. During their MRI, additional images will be acquired that
      measure the cerebral blood flow and cerebral venous oxygenation. These additional images will
      take up-to 10 extra minutes to acquire. This will increase the duration each subject spends
      under anesthesia, and in the MRI scanner by up-to a total of 10 extra minutes.

      Safety Assessment:

      To ensure that either propofol or sevoflurane are in clinical equipoise, all patients will be
      screened by an anesthesiologist. The experiment will occur in the standard-of-care clinical
      MRI environment. All patient safety and monitoring will remain in place. Throughout the
      induction, maintenance and recovery from anesthesia, all procedures will occur in the
      standard of care environment and will be overseen by trained clinical personnel.

      Efficacy Assessment:

      Cerebral blood flow and metabolism MRIs will be collected from all subjects.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Subjects will be randomized in a stratified, blocked study design. Stratification is based on two factors: gestational age (2 groups: ≥37 weeks and ≤37 weeks) and postmenstrual age at MRI (2 groups: ≥37 weeks and ≤37 weeks). Blocking of each stratum is performed in groups of 4.
primary purpose: Basic Science
masking: Double (Investigator, Outcomes Assessor)
masking description: Participant and care provider will be aware randomization status. Investigator and outcomes assessor will be masked.
measure: Change in cerebral blood flow (ml blood/100g/min)
time frame: Time points over which the change is assessed: change from (1) start of MRI, through (2) MRI completion, an average of 60 minutes.
description: Phase contrast (PC) acquisition via MRI will be used to assess any impact of anesthesia on cerebral blood flow.
measure: Change in cerebral metabolic rate of oxygen (ml O2/100g/min)
time frame: Time points over which the change is assessed: change from (1) start of MRI, through (2) MRI completion, an average of 60 minutes.
description: T2 relaxation under spin tagging (TRUST) acquisition via MRI will be used to assess any impact of anesthesia on cerebral metabolic rate of oxygen.
arm group label: Randomized propofol
arm group type: Active Comparator
description: Subject will receive propofol anesthesia during their MRI. Dosage form: injectable solution. Dosage: 100-300 mcg/kg/min, or as per clinical standard of care appropriate for specific subjects.
Frequency and duration: continuous infusion while undergoing MRI.
arm group label: Randomized sevoflurane
arm group type: Active Comparator
description: Subject will receive sevoflurane anesthesia during their MRI. Dosage form: volatile liquid for inhalation Dosing: 0-1 month full term neonate (3.3% in oxygen), 1-6 months old (3% in oxygen), 6 months to <3 years old (2.8% in oxygen), or as per clinical standard of care appropriate for specific subjects.
Frequency and duration: continuous infusion while undergoing MRI.
intervention type: Drug
intervention name: Propofol or Sevoflurane
description: Patient's will be randomized to the group receiving propofol, or the group receiving sevoflurane.
arm group label: Randomized propofol
arm group label: Randomized sevoflurane
criteria: 
gender: All
minimum age: N/A
maximum age: 1 Year
healthy volunteers: No
last name: Matthew Borzage, PhD
role: Principal Investigator
affiliation: Children's Hospital Los Angeles
last name: Hannah Wiseman
phone: 323-361-3963
email: hwiseman@chla.usc.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Propofol
mesh term: Sevoflurane
sharing ipd: No