<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/NCT04406818</url>
  </required_header>
  <id_info>
    <org_study_id>202106016</org_study_id>
    <secondary_id>R01NS121065</secondary_id>
    <nct_id>NCT04406818</nct_id>
  </id_info>
  <brief_title>Metabolic and Hemodynamic Reserve in Pediatric SCA</brief_title>
  <official_title>The Role of Metabolic and Hemodynamic Reserve in Age-Related Brain Vulnerability in Pediatric Sickle Cell Anemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to better understand how blood flow and metabolism&#xD;
      change can influence brain development in the early decades of life. SCA participants and&#xD;
      healthy controls are age and sex-matched for comparison. Within the SCA cohort, children with&#xD;
      infarcts may have thinner cortices than those without, reflecting a greater loss.&#xD;
&#xD;
      The investigators will examine brain blood flow and metabolism using magnetic resonance&#xD;
      imaging (MRI). The brain's blood vessels expand and constrict to regulate blood flow based on&#xD;
      the brain's needs. The amount of expanding and contracting the blood vessels may vary by age.&#xD;
      The brain's blood flow changes in small ways during everyday activities, such exercise, deep&#xD;
      concentration, or normal brain growth. Significant illness or psychological stress may&#xD;
      increase the brain's metabolic demand or cause other bigger changes in blood flow. If blood&#xD;
      vessels are not able to expand to give more blood flow when metabolic demand is high, the&#xD;
      brain may not get all of the oxygen it needs. In extreme circumstances, if the brain is&#xD;
      unable to get enough oxygen for a long time, a stroke may occur. Sometimes small strokes&#xD;
      occur without other noticeable changes and are only detectable on an MRI. These are sometimes&#xD;
      called &quot;silent strokes.&quot; In less extreme circumstances, not having a full oxygen supply may&#xD;
      cause the brain to grow and develop more slowly than when it has a full supply.&#xD;
&#xD;
      One way to test the ability of blood vessels to expand is by measuring blood flow while&#xD;
      breathing in carbon dioxide. Carbon dioxide causes blood vessels in the brain to dilate&#xD;
      without increasing brain metabolism.&#xD;
&#xD;
      During this study participants may be asked to undergo a blood draw, MRI, cognitive&#xD;
      assessments, and brief questionnaires. The study team will use a special mask to control the&#xD;
      amount of carbon dioxide the participants breathe in.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 30, 2021</start_date>
  <completion_date type="Anticipated">March 31, 2026</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2026</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Gray Matter cortical thickness</measure>
    <time_frame>3 years</time_frame>
    <description>Mean whole brain cortical thickness on high resolution T1 images</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total Brain volume</measure>
    <time_frame>3 years</time_frame>
    <description>Total brain volume (gray matter and white matter) on high resolution T1 image</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cerebrovascular Reactivity</measure>
    <time_frame>15 minutes</time_frame>
    <description>Change in blood flow as measured by MRI in response to carbon dioxide</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Child, Only</condition>
  <condition>Brain Diseases</condition>
  <condition>Sickle Cell Disease</condition>
  <condition>Anemia, Sickle Cell</condition>
  <arm_group>
    <arm_group_label>Healthy Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Sickle Cell Anemia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carbon Dioxide</intervention_name>
    <description>Participants inhale carbon dioxide while in magnetic resonance imaging scan to measure cerebrovascular reactivity</description>
    <arm_group_label>Healthy Control</arm_group_label>
    <arm_group_label>Sickle Cell Anemia</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Healthy Controls:&#xD;
&#xD;
          -  Healthy controls ages 4-21 years of age&#xD;
&#xD;
          -  Able to participate in MRI scan without sedation&#xD;
&#xD;
          -  Not currently pregnant&#xD;
&#xD;
          -  No significant psychiatric history, defined as having a severe psychiatric diagnosis,&#xD;
             per PI discretion&#xD;
&#xD;
          -  No history of epilepsy&#xD;
&#xD;
          -  No history of stroke or cerebrovascular disease&#xD;
&#xD;
          -  May have occasional headaches if not taking a daily preventative medication for&#xD;
             headaches&#xD;
&#xD;
          -  Not on vasodilatory medication, such as sildenafil or verapamil&#xD;
&#xD;
        Sickle Cell Anemia Participants:&#xD;
&#xD;
          -  Ages 4-21 years of age&#xD;
&#xD;
          -  Hb SS or SBeta-thal&#xD;
&#xD;
          -  Able to participate in MRI scan without sedation&#xD;
&#xD;
          -  Not currently pregnant&#xD;
&#xD;
          -  Not on vasodilatory medication, such as sildenafil or verapamil&#xD;
&#xD;
          -  No known vasculopathy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Years</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kristin P Guilliams, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kristin P Guilliams, MD</last_name>
    <phone>3144546120</phone>
    <email>kristinguilliams@wustl.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Washington University in St. Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristin P Guillliams, MD</last_name>
      <phone>314-454-6120</phone>
      <email>kristinguilliams@wustl.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>August 24, 2023</last_update_submitted>
  <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sickle cell anemia</keyword>
  <keyword>cerebrovascular reactivity</keyword>
  <keyword>cerebral oxygen metabolism</keyword>
  <keyword>cortical thickness</keyword>
  <keyword>gray matter</keyword>
  <keyword>carbon dioxide</keyword>
  <keyword>magnetic resonance imaging</keyword>
  <keyword>brain development</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Anemia, Sickle Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The proposed research assets will include MRI scan data and CO2 breathing data from 120 subjects, including pediatric subjects. As children are a vulnerable population, the project team will make the data (with any personally identifiable information redacted) available to qualified investigators under a data sharing agreement that provides for (1) a commitment to using for research purposes only, (2) a commitment to securing the data using appropriate computer technology, and (3) a commitment to destroying the data after analyses are completed. This will be available upon request within 6 months of the grant period ending.</ipd_description>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>At study conclusion</ipd_time_frame>
    <ipd_access_criteria>Upon request by qualified researchers</ipd_access_criteria>
  </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/NCT04406818
org study id: 202106016
secondary id: R01NS121065
nct id: NCT04406818
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this research study is to better understand how blood flow and metabolism
      change can influence brain development in the early decades of life. SCA participants and
      healthy controls are age and sex-matched for comparison. Within the SCA cohort, children with
      infarcts may have thinner cortices than those without, reflecting a greater loss.

      The investigators will examine brain blood flow and metabolism using magnetic resonance
      imaging (MRI). The brain's blood vessels expand and constrict to regulate blood flow based on
      the brain's needs. The amount of expanding and contracting the blood vessels may vary by age.
      The brain's blood flow changes in small ways during everyday activities, such exercise, deep
      concentration, or normal brain growth. Significant illness or psychological stress may
      increase the brain's metabolic demand or cause other bigger changes in blood flow. If blood
      vessels are not able to expand to give more blood flow when metabolic demand is high, the
      brain may not get all of the oxygen it needs. In extreme circumstances, if the brain is
      unable to get enough oxygen for a long time, a stroke may occur. Sometimes small strokes
      occur without other noticeable changes and are only detectable on an MRI. These are sometimes
      called "silent strokes." In less extreme circumstances, not having a full oxygen supply may
      cause the brain to grow and develop more slowly than when it has a full supply.

      One way to test the ability of blood vessels to expand is by measuring blood flow while
      breathing in carbon dioxide. Carbon dioxide causes blood vessels in the brain to dilate
      without increasing brain metabolism.

      During this study participants may be asked to undergo a blood draw, MRI, cognitive
      assessments, and brief questionnaires. The study team will use a special mask to control the
      amount of carbon dioxide the participants breathe in.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Gray Matter cortical thickness
time frame: 3 years
description: Mean whole brain cortical thickness on high resolution T1 images
measure: Total Brain volume
time frame: 3 years
description: Total brain volume (gray matter and white matter) on high resolution T1 image
measure: Cerebrovascular Reactivity
time frame: 15 minutes
description: Change in blood flow as measured by MRI in response to carbon dioxide
arm group label: Healthy Control
arm group type: Active Comparator
arm group label: Sickle Cell Anemia
arm group type: Active Comparator
intervention type: Drug
intervention name: Carbon Dioxide
description: Participants inhale carbon dioxide while in magnetic resonance imaging scan to measure cerebrovascular reactivity
arm group label: Healthy Control
arm group label: Sickle Cell Anemia
criteria: 
gender: All
minimum age: 4 Years
maximum age: 21 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kristin P Guilliams, MD
role: Principal Investigator
affiliation: Washington University School of Medicine
last name: Kristin P Guilliams, MD
phone: 3144546120
email: kristinguilliams@wustl.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Brain Diseases
mesh term: Anemia
mesh term: Anemia, Sickle Cell
sharing ipd: Yes
ipd description: The proposed research assets will include MRI scan data and CO2 breathing data from 120 subjects, including pediatric subjects. As children are a vulnerable population, the project team will make the data (with any personally identifiable information redacted) available to qualified investigators under a data sharing agreement that provides for (1) a commitment to using for research purposes only, (2) a commitment to securing the data using appropriate computer technology, and (3) a commitment to destroying the data after analyses are completed. This will be available upon request within 6 months of the grant period ending.
ipd info type: Informed Consent Form (ICF)
ipd time frame: At study conclusion
ipd access criteria: Upon request by qualified researchers