<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/NCT02225808</url>
  </required_header>
  <id_info>
    <org_study_id>1211011144</org_study_id>
    <nct_id>NCT02225808</nct_id>
  </id_info>
  <brief_title>Neural Mechanisms of CBT for Anxiety in Autism (Open Pilot Study)</brief_title>
  <official_title>Neural Mechanisms of Cognitive-Behavioral Therapy for Anxiety in Children With Autism Spectrum Disorder: A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open, pilot study of neural mechanisms of cognitive-behavioral therapy for anxiety&#xD;
      in children with high-functioning autism spectrum disorder (ASD). In addition to the core&#xD;
      symptoms, approximately forty percent of children with ASD exhibit clinically significant&#xD;
      levels of anxiety. Cognitive-Behavioral Therapy (CBT) is a promising treatment for anxiety in&#xD;
      children with high-functioning ASD, but the neural mechanisms of this treatment have not been&#xD;
      studied. CBT teaches emotion regulation skills such as cognitive reappraisal, followed by&#xD;
      behavioral exposure to anxiety-provoking situations. The investigators propose to investigate&#xD;
      the neural mechanisms of CBT for anxiety by evaluating fMRI indices of socioemotional&#xD;
      functioning before and after treatment in children, ages 8 to 14, with high-functioning ASD.&#xD;
      Dysfunction of the amygdala and its connectivity with prefrontal cortex has been implicated&#xD;
      in co-occurring ASD and anxiety. In the investigators research, compared to typically&#xD;
      developing controls, children with ASD have shown lower activation in several regions of&#xD;
      prefrontal cortex and a lack of down-regulation in the amygdala during a task of emotion&#xD;
      regulation. Based on these observations, the investigators propose that a positive response&#xD;
      to CBT for anxiety in children with ASD will be associated with increased activation of&#xD;
      several regions in the prefrontal cortex as well as increased functional connectivity between&#xD;
      prefrontal regions the amygdala during the task of emotion regulation. The primary aim of&#xD;
      this pilot study is to examine the effects of CBT on the neural basis of anxiety in ASD by&#xD;
      collecting fMRI data during emotion regulation, face perception, and rest before and after&#xD;
      treatment. The investigators hypothesize that CBT will increase prefrontal activity, decrease&#xD;
      amygdala reactivity, and enhance amygdala-prefrontal functional connectivity during emotion&#xD;
      regulation. The investigators also hypothesize that CBT will decrease amygdala reactivity&#xD;
      during perception of emotional faces. Additional analyses will be conducted to explore change&#xD;
      in resting-state functional connectivity before and after CBT for anxiety in children with&#xD;
      ASD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2016</primary_completion_date>
  <phase>N/A</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>functional magnetic resonance imaging (fMRI)</measure>
    <time_frame>baseline (week 0)</time_frame>
    <description>fMRI scanning with tasks of emotion regulation and social perception</description>
  </primary_outcome>
  <primary_outcome>
    <measure>functional magnetic resonance imaging (fMRI)</measure>
    <time_frame>endpoint (week 12)</time_frame>
    <description>fMRI scanning with tasks of emotion regulation and social perception</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Multidimensional anxiety scale for children (MASC)</measure>
    <time_frame>baseline (week 0)</time_frame>
    <description>parent rating of child anxiety</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multidimensional anxiety scale for children (MASC)</measure>
    <time_frame>endpoint (week 12)</time_frame>
    <description>parent rating of child anxiety</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pediatric Anxiety Rating Scale (PARS)</measure>
    <time_frame>baseline (week 0)</time_frame>
    <description>clinician rating of anxiety based on an interview with parent and child</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pediatric Anxiety Rating Scale (PARS)</measure>
    <time_frame>endpoint (week 12)</time_frame>
    <description>clinician rating of anxiety based on an interview with parent and child</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Autism</condition>
  <condition>Autism Spectrum Disorder</condition>
  <condition>Anxiety</condition>
  <arm_group>
    <arm_group_label>CBT for anxiety in autism</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cognitive-behavioral therapy (CBT) teaches skills for coping with anxiety and consist of 12 weekly sessions. CBT is conducted with child and parent.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>CBT for anxiety in autism</intervention_name>
    <arm_group_label>CBT for anxiety in autism</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and females, ages 8 to 14 inclusive.&#xD;
&#xD;
          2. DSM-V diagnosis of autism spectrum disorder.&#xD;
&#xD;
          3. DSM-V diagnosis of generalized anxiety disorder, separation anxiety disorder, or&#xD;
             social phobia.&#xD;
&#xD;
          4. Score &gt; 19 on the 20 Item Anxiety scale of the Child and Adolescent Symptom Inventory.&#xD;
&#xD;
          5. Full Scale IQ and Verbal IQ &gt; 70.&#xD;
&#xD;
          6. Unmedicated or on stable medication for irritability, ADHD, anxiety, or depression for&#xD;
             at least 6 weeks, with no planned changes for duration of study.&#xD;
&#xD;
        7. Subjects will be free of metal medical implants, and will have a body weight of less&#xD;
        than 250 lbs. and no claustrophobia. [These are necessitated by the safety requirements of&#xD;
        the fMRI.]&#xD;
&#xD;
        8. Child is an English speaker.&#xD;
&#xD;
        9. Child is able to meet fMRI data quality requirements at baseline [to enable pre- to&#xD;
        post-treatment comparison.]&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of a known serious medical condition in the child (based on medical history&#xD;
             or parent report) that would interfere with child and parent's ability to participate&#xD;
             in the study.&#xD;
&#xD;
          2. Presence of a current psychiatric diagnosis in the child that would require&#xD;
             alternative treatment (based on assessment by experienced study clinician).&#xD;
&#xD;
          3. Previous treatment with four or more sessions of CBT for anxiety. -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>14 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Denis Sukhodolsky, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale School of Medicine, Child Study Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Sukhodolsky DG, Bloch MH, Panza KE, Reichow B. Cognitive-behavioral therapy for anxiety in children with high-functioning autism: a meta-analysis. Pediatrics. 2013 Nov;132(5):e1341-50. doi: 10.1542/peds.2013-1193. Epub 2013 Oct 28.</citation>
    <PMID>24167175</PMID>
  </reference>
  <reference>
    <citation>Sukhodolsky DG, Scahill L, Gadow KD, Arnold LE, Aman MG, McDougle CJ, McCracken JT, Tierney E, Williams White S, Lecavalier L, Vitiello B. Parent-rated anxiety symptoms in children with pervasive developmental disorders: frequency and association with core autism symptoms and cognitive functioning. J Abnorm Child Psychol. 2008 Jan;36(1):117-28. doi: 10.1007/s10802-007-9165-9. Epub 2007 Aug 3.</citation>
    <PMID>17674186</PMID>
  </reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <last_update_submitted>January 10, 2020</last_update_submitted>
  <last_update_submitted_qc>January 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CBT</keyword>
  <keyword>autism</keyword>
  <keyword>anxiety</keyword>
  <keyword>treatment</keyword>
  <keyword>fMRI</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>
  <!-- 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/NCT02225808
org study id: 1211011144
nct id: NCT02225808
lead sponsor: 
has dmc: Yes
This is an open, pilot study of neural mechanisms of cognitive-behavioral therapy for anxiety
      in children with high-functioning autism spectrum disorder (ASD). In addition to the core
      symptoms, approximately forty percent of children with ASD exhibit clinically significant
      levels of anxiety. Cognitive-Behavioral Therapy (CBT) is a promising treatment for anxiety in
      children with high-functioning ASD, but the neural mechanisms of this treatment have not been
      studied. CBT teaches emotion regulation skills such as cognitive reappraisal, followed by
      behavioral exposure to anxiety-provoking situations. The investigators propose to investigate
      the neural mechanisms of CBT for anxiety by evaluating fMRI indices of socioemotional
      functioning before and after treatment in children, ages 8 to 14, with high-functioning ASD.
      Dysfunction of the amygdala and its connectivity with prefrontal cortex has been implicated
      in co-occurring ASD and anxiety. In the investigators research, compared to typically
      developing controls, children with ASD have shown lower activation in several regions of
      prefrontal cortex and a lack of down-regulation in the amygdala during a task of emotion
      regulation. Based on these observations, the investigators propose that a positive response
      to CBT for anxiety in children with ASD will be associated with increased activation of
      several regions in the prefrontal cortex as well as increased functional connectivity between
      prefrontal regions the amygdala during the task of emotion regulation. The primary aim of
      this pilot study is to examine the effects of CBT on the neural basis of anxiety in ASD by
      collecting fMRI data during emotion regulation, face perception, and rest before and after
      treatment. The investigators hypothesize that CBT will increase prefrontal activity, decrease
      amygdala reactivity, and enhance amygdala-prefrontal functional connectivity during emotion
      regulation. The investigators also hypothesize that CBT will decrease amygdala reactivity
      during perception of emotional faces. Additional analyses will be conducted to explore change
      in resting-state functional connectivity before and after CBT for anxiety in children with
      ASD.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: functional magnetic resonance imaging (fMRI)
time frame: baseline (week 0)
description: fMRI scanning with tasks of emotion regulation and social perception
measure: functional magnetic resonance imaging (fMRI)
time frame: endpoint (week 12)
description: fMRI scanning with tasks of emotion regulation and social perception
measure: Multidimensional anxiety scale for children (MASC)
time frame: baseline (week 0)
description: parent rating of child anxiety
measure: Multidimensional anxiety scale for children (MASC)
time frame: endpoint (week 12)
description: parent rating of child anxiety
measure: Pediatric Anxiety Rating Scale (PARS)
time frame: baseline (week 0)
description: clinician rating of anxiety based on an interview with parent and child
measure: Pediatric Anxiety Rating Scale (PARS)
time frame: endpoint (week 12)
description: clinician rating of anxiety based on an interview with parent and child
arm group label: CBT for anxiety in autism
arm group type: Experimental
description: Cognitive-behavioral therapy (CBT) teaches skills for coping with anxiety and consist of 12 weekly sessions. CBT is conducted with child and parent.
intervention type: Behavioral
intervention name: CBT for anxiety in autism
arm group label: CBT for anxiety in autism
criteria: 
gender: All
minimum age: 8 Years
maximum age: 14 Years
healthy volunteers: No
last name: Denis Sukhodolsky, Ph.D.
role: Principal Investigator
affiliation: Yale University
facility: 
country: United States
citation: Sukhodolsky DG, Bloch MH, Panza KE, Reichow B. Cognitive-behavioral therapy for anxiety in children with high-functioning autism: a meta-analysis. Pediatrics. 2013 Nov;132(5):e1341-50. doi: 10.1542/peds.2013-1193. Epub 2013 Oct 28.
PMID: 24167175
citation: Sukhodolsky DG, Scahill L, Gadow KD, Arnold LE, Aman MG, McDougle CJ, McCracken JT, Tierney E, Williams White S, Lecavalier L, Vitiello B. Parent-rated anxiety symptoms in children with pervasive developmental disorders: frequency and association with core autism symptoms and cognitive functioning. J Abnorm Child Psychol. 2008 Jan;36(1):117-28. doi: 10.1007/s10802-007-9165-9. Epub 2007 Aug 3.
PMID: 17674186
responsible party type: Sponsor
mesh term: Anxiety Disorders
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder