<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/NCT04436432</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00173329</org_study_id>
    <nct_id>NCT04436432</nct_id>
  </id_info>
  <brief_title>Phenomenology of Anxiety in Preschool Children With ASD</brief_title>
  <official_title>Phenomenology of Anxiety in Preschool Children With Autism Spectrum Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hugo W. Moser Research Institute at Kennedy Krieger, Inc.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hugo W. Moser Research Institute at Kennedy Krieger, Inc.</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>
      This study investigates the prevalence, phenomenology, and correlates of anxiety in preschool&#xD;
      children with autism spectrum disorder (ASD) across a two-year period. Attention bias to&#xD;
      threat, a potential objective marker of anxiety, also is examined using eye tracking methods.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Anxiety disorders in children with autism spectrum disorders (ASD) are one of the most&#xD;
      prevalent and impairing co-occurring conditions, affecting approximately 40% of the&#xD;
      population and causing major disruptions in school and family life. Research in typically&#xD;
      developing (TD) children suggests that anxiety usually emerges in the preschool years (3-5&#xD;
      years) and can result in future psychopathology. Early detection and treatment of childhood&#xD;
      anxiety in children with ASD can lead to improved clinical outcomes.&#xD;
&#xD;
      This study assesses the prevalence and phenomenology of anxiety in preschool children with&#xD;
      ASD utilizing an established and comprehensive measure of anxiety in children with ASD across&#xD;
      three time points (baseline, one year post, two years post).It also investigates the&#xD;
      association of child (e.g., ASD features) and parent (e.g., mental health, caregiver strain)&#xD;
      characteristics with anxiety cross-sectionally and longitudinally, to determine if certain&#xD;
      correlates predict or maintain future anxiety. Attention bias to threat stimuli and its&#xD;
      physiological correlates are also examined as potential objective markers of anxiety using&#xD;
      eye tracking and pupillometry methods.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 25, 2018</start_date>
  <completion_date type="Actual">July 1, 2021</completion_date>
  <primary_completion_date type="Actual">July 1, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Anxiety diagnostic status as measured by Anxiety Disorders Interview Schedule with Autism Addendum</measure>
    <time_frame>Anxiety diagnostic status will be measured through study completion, up to 24 months</time_frame>
    <description>Gold-standard semi-structured interview for assessing anxiety disorders and the ASA, a supplement to the ADIS that facilitates the use of this tool in children with ASD; clinical severity ratings range from 0 to 3 or 0 to 8; higher scores indicate more impairment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Attention to threat behavioral paradigms</measure>
    <time_frame>Attention to threat and correlated physiological arousal will be measured across the final 12 months of the study</time_frame>
    <description>Child's attention to threatening stimuli measured via eye tracking and correlated physiological response measures via pupillometry; more frequent saccades to threatening stimuli indicate higher attention bias to threat; greater pupil dilation indicates higher physiological arousal</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Child Behavior Checklist</measure>
    <time_frame>Anxiety and other psychiatric symptoms will be assessed through study completion, up to 24 months</time_frame>
    <description>parent and teacher report scale that measures child anxiety and other psychiatric symptoms;T scores range from 20 to 100; Syndrome scales: T-scores over 65 indicate clinically significant symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preschool Anxiety Scale - Revised</measure>
    <time_frame>Anxiety will be assessed through study completion, up to 24 months</time_frame>
    <description>parent and teacher report scale measuring levels of anxiety in preschool aged children; scores range from 0 to 112; higher scores indicate higher anxiety</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Screen for Child Anxiety Related Disorders</measure>
    <time_frame>Anxiety will be assessed through study completion, up to 24 months</time_frame>
    <description>parent and teacher report scale measuring levels of anxiety in children 6 or older; scores range from 0 to 114; higher scores indicate higher anxiety</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response to Uncertainty and Low Environmental Stability Scale</measure>
    <time_frame>Intolerance of uncertainty will be assessed through study completion, up to 24 months</time_frame>
    <description>parent and teacher report scale measuring response to uncertainty and low environmental structure in children; scores range from 1 to 5; higher scores indicate higher intolerance of uncertainty</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Social Responsiveness Scale</measure>
    <time_frame>ASD symptoms will be assessed through study completion, up to 24 months</time_frame>
    <description>parent report scale that assesses the presence and severity of social impairment in children; T-scores range from 20 to 100; higher scores indicate higher ASD severity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emotion Regulation Checklist</measure>
    <time_frame>Emotional regulation will be assessed through study completion, up to 24 months</time_frame>
    <description>parent report scale that assesses emotion regulation capacities in children; scores range from 24 to 96; higher scores indicate higher impairment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Children's Sleep Habits Questionnaire</measure>
    <time_frame>Sleep habits will be assessed across the final 12 months of the study</time_frame>
    <description>parent report questionnaire that measures sleep habits in children; scores range from 45 to 135; higher scores indicate greater frequency of sleep problems</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Anxiety and Depression scale</measure>
    <time_frame>Parental anxiety and depression will be assessed through the completion of the study, up to 24 months</time_frame>
    <description>screening tool that will be used to capture clinical anxiety and depression in parents; scores range from 0 to 21; higher scores indicate higher anxiety and/or depression symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intolerance of Uncertainty Scale</measure>
    <time_frame>Parental intolerance of uncertainty will be assessed through the completion of the study, up to 24 months</time_frame>
    <description>scale that will be used to measure parental responses to uncertainty, ambiguous situations and the future; scores range from 12 to 60; higher scores indicate higher intolerance of uncertainty</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Family Accommodation Scale</measure>
    <time_frame>Parental accommodation will be assessed through the completion of the study, up to 24 months</time_frame>
    <description>assesses parental accommodation of child's interfering symptoms; scores range from 0 to 36; higher scores indicate higher parental accommodation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Burden Assessment Scale</measure>
    <time_frame>Parental strain will be assessed through study completion, up to 24 months</time_frame>
    <description>measures strain (thoughts, feelings, disruption) associated with having a child with a neurodevelopmental disorder; scores range from 19 to 76; higher scores indicate greater family burden</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Broader Autism Phenotype</measure>
    <time_frame>Parental autism features will be assessed through study completion, up to 24 months</time_frame>
    <description>self-report scale that measures broader autism symptoms in the parent; scores range from 36 to 216; higher scores indicate greater severity of autism features</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">75</enrollment>
  <condition>Anxiety</condition>
  <condition>Autism Spectrum Disorder</condition>
  <arm_group>
    <arm_group_label>Assessment</arm_group_label>
    <description>Children with ASD ages 3-5 years at baseline</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Clinical and community based sample&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 3 years 0 months to 5 years 11 months;&#xD;
&#xD;
          -  DSM-5 ASD diagnosis based on clinical impressions and results of the Autism Diagnostic&#xD;
             Observation Schedule-2 (ADOS-2)&#xD;
&#xD;
          -  Child resides with at least one biological parent&#xD;
&#xD;
          -  Parents are English speaking&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of psychological trauma&#xD;
&#xD;
          -  History of neurologic illness&#xD;
&#xD;
          -  Parent substance abuse, bipolar disorder, psychosis&#xD;
&#xD;
          -  Parents require support from a medical interpreter&#xD;
&#xD;
          -  Child displays severe behavior challenges&#xD;
&#xD;
          -  Severe eyesight or hearing impairments that may interfere with the protocols&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>36 Months</minimum_age>
    <maximum_age>71 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Roma A Vasa, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hugo W. Moser Research Institute at Kennedy Krieger, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kennedy Krieger Institute</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.kennedykrieger.org/sites/default/files/library/documents/patient-care/centers-and-programs/center-for-autism-and-related-disorders/FINAL_IRB00173329_Study%20flyer_revised%20(1).pdf</url>
    <description>Study Flier</description>
  </link>
  <reference>
    <citation>Vasa RA, Kreiser NL, Keefer A, Singh V, Mostofsky SH. Relationships between autism spectrum disorder and intolerance of uncertainty. Autism Res. 2018 Apr;11(4):636-644. doi: 10.1002/aur.1916. Epub 2018 Jan 7.</citation>
    <PMID>29316350</PMID>
  </reference>
  <reference>
    <citation>Vasa RA, Keefer A, Reaven J, South M, White SW. Priorities for Advancing Research on Youth with Autism Spectrum Disorder and Co-occurring Anxiety. J Autism Dev Disord. 2018 Mar;48(3):925-934. doi: 10.1007/s10803-017-3320-0.</citation>
    <PMID>29164436</PMID>
  </reference>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>November 23, 2021</last_update_submitted>
  <last_update_submitted_qc>November 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 24, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hugo W. Moser Research Institute at Kennedy Krieger, Inc.</investigator_affiliation>
    <investigator_full_name>Roma Vasa</investigator_full_name>
    <investigator_title>Director of Psychiatric Services</investigator_title>
  </responsible_party>
  <keyword>Autism</keyword>
  <keyword>Anxiety</keyword>
  <keyword>Eye tracking</keyword>
  <keyword>Preschool</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anxiety Disorders</mesh_term>
    <mesh_term>Autistic Disorder</mesh_term>
    <mesh_term>Autism Spectrum Disorder</mesh_term>
  </condition_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/NCT04436432
org study id: IRB00173329
nct id: NCT04436432
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study investigates the prevalence, phenomenology, and correlates of anxiety in preschool
      children with autism spectrum disorder (ASD) across a two-year period. Attention bias to
      threat, a potential objective marker of anxiety, also is examined using eye tracking methods.
Anxiety disorders in children with autism spectrum disorders (ASD) are one of the most
      prevalent and impairing co-occurring conditions, affecting approximately 40% of the
      population and causing major disruptions in school and family life. Research in typically
      developing (TD) children suggests that anxiety usually emerges in the preschool years (3-5
      years) and can result in future psychopathology. Early detection and treatment of childhood
      anxiety in children with ASD can lead to improved clinical outcomes.

      This study assesses the prevalence and phenomenology of anxiety in preschool children with
      ASD utilizing an established and comprehensive measure of anxiety in children with ASD across
      three time points (baseline, one year post, two years post).It also investigates the
      association of child (e.g., ASD features) and parent (e.g., mental health, caregiver strain)
      characteristics with anxiety cross-sectionally and longitudinally, to determine if certain
      correlates predict or maintain future anxiety. Attention bias to threat stimuli and its
      physiological correlates are also examined as potential objective markers of anxiety using
      eye tracking and pupillometry methods.
observational model: Cohort
time perspective: Prospective
measure: Anxiety diagnostic status as measured by Anxiety Disorders Interview Schedule with Autism Addendum
time frame: Anxiety diagnostic status will be measured through study completion, up to 24 months
description: Gold-standard semi-structured interview for assessing anxiety disorders and the ASA, a supplement to the ADIS that facilitates the use of this tool in children with ASD; clinical severity ratings range from 0 to 3 or 0 to 8; higher scores indicate more impairment
measure: Attention to threat behavioral paradigms
time frame: Attention to threat and correlated physiological arousal will be measured across the final 12 months of the study
description: Child's attention to threatening stimuli measured via eye tracking and correlated physiological response measures via pupillometry; more frequent saccades to threatening stimuli indicate higher attention bias to threat; greater pupil dilation indicates higher physiological arousal
measure: Child Behavior Checklist
time frame: Anxiety and other psychiatric symptoms will be assessed through study completion, up to 24 months
description: parent and teacher report scale that measures child anxiety and other psychiatric symptoms;T scores range from 20 to 100; Syndrome scales: T-scores over 65 indicate clinically significant symptoms
measure: Preschool Anxiety Scale - Revised
time frame: Anxiety will be assessed through study completion, up to 24 months
description: parent and teacher report scale measuring levels of anxiety in preschool aged children; scores range from 0 to 112; higher scores indicate higher anxiety
measure: Screen for Child Anxiety Related Disorders
time frame: Anxiety will be assessed through study completion, up to 24 months
description: parent and teacher report scale measuring levels of anxiety in children 6 or older; scores range from 0 to 114; higher scores indicate higher anxiety
measure: Response to Uncertainty and Low Environmental Stability Scale
time frame: Intolerance of uncertainty will be assessed through study completion, up to 24 months
description: parent and teacher report scale measuring response to uncertainty and low environmental structure in children; scores range from 1 to 5; higher scores indicate higher intolerance of uncertainty
measure: Social Responsiveness Scale
time frame: ASD symptoms will be assessed through study completion, up to 24 months
description: parent report scale that assesses the presence and severity of social impairment in children; T-scores range from 20 to 100; higher scores indicate higher ASD severity
measure: Emotion Regulation Checklist
time frame: Emotional regulation will be assessed through study completion, up to 24 months
description: parent report scale that assesses emotion regulation capacities in children; scores range from 24 to 96; higher scores indicate higher impairment
measure: The Children's Sleep Habits Questionnaire
time frame: Sleep habits will be assessed across the final 12 months of the study
description: parent report questionnaire that measures sleep habits in children; scores range from 45 to 135; higher scores indicate greater frequency of sleep problems
measure: Hospital Anxiety and Depression scale
time frame: Parental anxiety and depression will be assessed through the completion of the study, up to 24 months
description: screening tool that will be used to capture clinical anxiety and depression in parents; scores range from 0 to 21; higher scores indicate higher anxiety and/or depression symptoms
measure: Intolerance of Uncertainty Scale
time frame: Parental intolerance of uncertainty will be assessed through the completion of the study, up to 24 months
description: scale that will be used to measure parental responses to uncertainty, ambiguous situations and the future; scores range from 12 to 60; higher scores indicate higher intolerance of uncertainty
measure: Family Accommodation Scale
time frame: Parental accommodation will be assessed through the completion of the study, up to 24 months
description: assesses parental accommodation of child's interfering symptoms; scores range from 0 to 36; higher scores indicate higher parental accommodation
measure: Burden Assessment Scale
time frame: Parental strain will be assessed through study completion, up to 24 months
description: measures strain (thoughts, feelings, disruption) associated with having a child with a neurodevelopmental disorder; scores range from 19 to 76; higher scores indicate greater family burden
measure: Broader Autism Phenotype
time frame: Parental autism features will be assessed through study completion, up to 24 months
description: self-report scale that measures broader autism symptoms in the parent; scores range from 36 to 216; higher scores indicate greater severity of autism features
arm group label: Assessment
description: Children with ASD ages 3-5 years at baseline
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 36 Months
maximum age: 71 Months
healthy volunteers: No
last name: Roma A Vasa, M.D.
role: Principal Investigator
affiliation: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
facility: 
country: United States
url: https://www.kennedykrieger.org/sites/default/files/library/documents/patient-care/centers-and-programs/center-for-autism-and-related-disorders/FINAL_IRB00173329_Study%20flyer_revised%20(1).pdf
description: Study Flier
citation: Vasa RA, Kreiser NL, Keefer A, Singh V, Mostofsky SH. Relationships between autism spectrum disorder and intolerance of uncertainty. Autism Res. 2018 Apr;11(4):636-644. doi: 10.1002/aur.1916. Epub 2018 Jan 7.
PMID: 29316350
citation: Vasa RA, Keefer A, Reaven J, South M, White SW. Priorities for Advancing Research on Youth with Autism Spectrum Disorder and Co-occurring Anxiety. J Autism Dev Disord. 2018 Mar;48(3):925-934. doi: 10.1007/s10803-017-3320-0.
PMID: 29164436
responsible party type: Principal Investigator
investigator affiliation: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
investigator full name: Roma Vasa
investigator title: Director of Psychiatric Services
mesh term: Anxiety Disorders
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder
sharing ipd: No