<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/NCT02187445</url>
  </required_header>
  <id_info>
    <org_study_id>DDCF2014086</org_study_id>
    <nct_id>NCT02187445</nct_id>
  </id_info>
  <brief_title>Inhaled Corticosteroid Use to Prevent Acute Chest Syndrome Recurrence in Children Between 1 and 4 With Sickle Cell Disease: a Feasibility Trial</brief_title>
  <official_title>Inhaled Corticosteroid Use to Prevent Acute Chest Syndrome Recurrence in Children Between 1 and 4 With Sickle Cell Disease: a Feasibility Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's National Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Acute and chronic pulmonary complications with concomitant inflammatory response are a&#xD;
      leading cause of morbidity and mortality in children with sickle cell disease (SCD). Acute&#xD;
      chest syndrome (ACS), defined broadly as an increase in respiratory effort, fever and new&#xD;
      radiodensity on chest x-ray, is a major cause of death in children and adults with SCD. There&#xD;
      is a high rate of ACS in children between 1 and 4 years of age that is associated with an&#xD;
      asthma diagnosis, and children with ACS events before 4 years of age have a 50% rate of being&#xD;
      hospitalized for either ACS or pain within 1 year of admission. For children with SCD that&#xD;
      develop ACS, the investigators propose that the use of budesonide inhalation suspension (BIS)&#xD;
      will attenuate pulmonary inflammation after an ACS episode and will decrease future&#xD;
      vaso-occlusive pain and ACS episodes. Through a single-arm prospective feasibility trial and&#xD;
      in preparation for a limited-institution randomized trial, the investigators plan to test the&#xD;
      following primary hypothesis for a phase III definitive trial: In children with SCD admitted&#xD;
      to the hospital for an ACS episode between 1 and 4 years of age, low dose BIS for 6 months&#xD;
      will result in a 50% reduction in the recurrent incidence rate of ACS or pain requiring&#xD;
      hospitalization. Through this trial, the investigators will determine the acceptability of&#xD;
      and adherence to BIS in the study population. The investigators will track respiratory&#xD;
      symptoms in cases versus controls over 6 months. Finally, the investigators will explore the&#xD;
      impact of BIS on biological correlates (sVCAM-1).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">February 13, 2017</completion_date>
  <primary_completion_date type="Actual">December 2016</primary_completion_date>
  <phase>Phase 1</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The acceptability of budesonide inhalation suspension</measure>
    <time_frame>6 Months</time_frame>
    <description>Specific Aim 1: To determine the acceptability of budesonide inhalation suspension (BIS) 0.5 QD for 6 months for children with SCD that develop ACS between 1 and 4 years of age (n=10). We will determine the proportions of eligible families who were willing to participate and families that enrolled and elected to stay throughout the six months of the trial. We will also assess adherence to BIS using the Morisky scale; this will be our primary outcome. If the participation rate for the trial is less than 60%, the dropout rate is greater than 20%, or if our adherence rate is poor as measured by the Morisky scale, then alternative strategies for recruitment, retention and adherence must be considered.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The impact of BIS on biological correlates of inflammation.</measure>
    <time_frame>12 weeks (or between 8-16 weeks) and at 24 weeks (or between 20-28 weeks)</time_frame>
    <description>Specific Aim 2: To explore the impact of BIS on biological correlates of inflammation. For this purpose, a blood sample measurement will be taken at baseline, at 12 weeks (between 8-16 weeks) and at 24 weeks (between 20-28 weeks), as per routine clinic visits. The research visit will be coordinated with the standard care visits and phlebotomy. Soluble vascular cell adhesion molecule-1 (sVCAM-1), a marker of chronic vasculopathy, will be the primary measure of vascular injury. Secondary outcome measures will include additional inflammatory markers (sP-selectin, sE-selectin, IL-1B, IL-6, TNFα, IFN-y, leukotrienes).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Quality of life for guardians of children with sickle cell disease and ACS</measure>
    <time_frame>0 weeks, 12 weeks (or between 8-16 weeks) and at 24 weeks (or between 20-28 weeks)</time_frame>
    <description>At each clinic visit, we will also collect patient-centered outcomes, assessing caregiver burden. Data will be collected using the Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), validated for parents of children with asthma.</description>
  </other_outcome>
  <other_outcome>
    <measure>Respiratory symptoms</measure>
    <time_frame>6 months, monthly</time_frame>
    <description>Using the TRACK survey, validated for guardians of children under the age of 5 years, we will call families monthly to collect data on respiratory symptoms over the course of the study.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Sickle Cell Disease</condition>
  <condition>Asthma</condition>
  <condition>Acute Chest Syndrome</condition>
  <arm_group>
    <arm_group_label>Budesonide inhalation suspension</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To determine the acceptability of budesonide inhalation suspension (BIS) 0.5 QD for 6 months for children with SCD that develop ACS between 1 and 4 years of age (n=10).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Budesonide inhalation suspension</intervention_name>
    <description>To determine the acceptability of budesonide inhalation suspension (BIS) 0.5 QD for 6 months for children with SCD that develop ACS between 1 and 4 years of age (n=10).</description>
    <arm_group_label>Budesonide inhalation suspension</arm_group_label>
    <other_name>inhaled corticosteroids</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1) confirmed diagnosis of sickle cell disease (SCD)&#xD;
&#xD;
          -  2) age between 1 and 4 years (must have reached 1st but not yet 4th birthday)&#xD;
&#xD;
          -  3) a prior diagnosis of ACS, defined as acute respiratory illness with a new&#xD;
             radiodensity on CXR, and one of the following: fever (temperature &gt; 38.50C), decrease&#xD;
             in oxygen saturation more than 3% from baseline, or increase in respiratory rate above&#xD;
             baseline&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1) patients already taking inhaled corticosteroids&#xD;
&#xD;
          -  2) those receiving blood transfusions for elevated TCD or strokes&#xD;
&#xD;
          -  3) presents over 2 weeks after discharge from hospital following initial ACS episode.&#xD;
&#xD;
        Participants may be on hydroxyurea and participate in this trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>4 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael R DeBaun, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232-9000</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>June 27, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <last_update_submitted>February 16, 2017</last_update_submitted>
  <last_update_submitted_qc>February 16, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University</investigator_affiliation>
    <investigator_full_name>Michael DeBaun</investigator_full_name>
    <investigator_title>Professor of Pediatrics and Medicine, Vice Chair of Clinical Research in Pediatrics, JC Peterson Endowed Chair in Pediatrics, Director, Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease</investigator_title>
  </responsible_party>
  <keyword>Sickle Cell Disease</keyword>
  <keyword>Budesonide inhalation suspension</keyword>
  <keyword>Acute Chest Syndrome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Chest Syndrome</mesh_term>
    <mesh_term>Anemia, Sickle Cell</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Budesonide</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02187445
org study id: DDCF2014086
nct id: NCT02187445
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Acute and chronic pulmonary complications with concomitant inflammatory response are a
      leading cause of morbidity and mortality in children with sickle cell disease (SCD). Acute
      chest syndrome (ACS), defined broadly as an increase in respiratory effort, fever and new
      radiodensity on chest x-ray, is a major cause of death in children and adults with SCD. There
      is a high rate of ACS in children between 1 and 4 years of age that is associated with an
      asthma diagnosis, and children with ACS events before 4 years of age have a 50% rate of being
      hospitalized for either ACS or pain within 1 year of admission. For children with SCD that
      develop ACS, the investigators propose that the use of budesonide inhalation suspension (BIS)
      will attenuate pulmonary inflammation after an ACS episode and will decrease future
      vaso-occlusive pain and ACS episodes. Through a single-arm prospective feasibility trial and
      in preparation for a limited-institution randomized trial, the investigators plan to test the
      following primary hypothesis for a phase III definitive trial: In children with SCD admitted
      to the hospital for an ACS episode between 1 and 4 years of age, low dose BIS for 6 months
      will result in a 50% reduction in the recurrent incidence rate of ACS or pain requiring
      hospitalization. Through this trial, the investigators will determine the acceptability of
      and adherence to BIS in the study population. The investigators will track respiratory
      symptoms in cases versus controls over 6 months. Finally, the investigators will explore the
      impact of BIS on biological correlates (sVCAM-1).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: The acceptability of budesonide inhalation suspension
time frame: 6 Months
description: Specific Aim 1: To determine the acceptability of budesonide inhalation suspension (BIS) 0.5 QD for 6 months for children with SCD that develop ACS between 1 and 4 years of age (n=10). We will determine the proportions of eligible families who were willing to participate and families that enrolled and elected to stay throughout the six months of the trial. We will also assess adherence to BIS using the Morisky scale; this will be our primary outcome. If the participation rate for the trial is less than 60%, the dropout rate is greater than 20%, or if our adherence rate is poor as measured by the Morisky scale, then alternative strategies for recruitment, retention and adherence must be considered.
measure: The impact of BIS on biological correlates of inflammation.
time frame: 12 weeks (or between 8-16 weeks) and at 24 weeks (or between 20-28 weeks)
description: Specific Aim 2: To explore the impact of BIS on biological correlates of inflammation. For this purpose, a blood sample measurement will be taken at baseline, at 12 weeks (between 8-16 weeks) and at 24 weeks (between 20-28 weeks), as per routine clinic visits. The research visit will be coordinated with the standard care visits and phlebotomy. Soluble vascular cell adhesion molecule-1 (sVCAM-1), a marker of chronic vasculopathy, will be the primary measure of vascular injury. Secondary outcome measures will include additional inflammatory markers (sP-selectin, sE-selectin, IL-1B, IL-6, TNFα, IFN-y, leukotrienes).
measure: Quality of life for guardians of children with sickle cell disease and ACS
time frame: 0 weeks, 12 weeks (or between 8-16 weeks) and at 24 weeks (or between 20-28 weeks)
description: At each clinic visit, we will also collect patient-centered outcomes, assessing caregiver burden. Data will be collected using the Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), validated for parents of children with asthma.
measure: Respiratory symptoms
time frame: 6 months, monthly
description: Using the TRACK survey, validated for guardians of children under the age of 5 years, we will call families monthly to collect data on respiratory symptoms over the course of the study.
arm group label: Budesonide inhalation suspension
arm group type: Experimental
description: To determine the acceptability of budesonide inhalation suspension (BIS) 0.5 QD for 6 months for children with SCD that develop ACS between 1 and 4 years of age (n=10).
intervention type: Drug
intervention name: Budesonide inhalation suspension
description: To determine the acceptability of budesonide inhalation suspension (BIS) 0.5 QD for 6 months for children with SCD that develop ACS between 1 and 4 years of age (n=10).
arm group label: Budesonide inhalation suspension
other name: inhaled corticosteroids
criteria: 
gender: All
minimum age: 1 Year
maximum age: 4 Years
healthy volunteers: No
last name: Michael R DeBaun, MD, MPH
role: Principal Investigator
affiliation: Vanderbilt University Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University
investigator full name: Michael DeBaun
investigator title: Professor of Pediatrics and Medicine, Vice Chair of Clinical Research in Pediatrics, JC Peterson Endowed Chair in Pediatrics, Director, Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease
mesh term: Acute Chest Syndrome
mesh term: Anemia, Sickle Cell
mesh term: Syndrome
mesh term: Recurrence
mesh term: Budesonide