<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/NCT03254264</url>
  </required_header>
  <id_info>
    <org_study_id>2015-A00696-43</org_study_id>
    <nct_id>NCT03254264</nct_id>
  </id_info>
  <brief_title>Impact of Early Interventions on Neurocognitive Profile of Children With Autism Spectrum Disorder</brief_title>
  <acronym>IDEAEYE</acronym>
  <official_title>Impact of Early Intervention on Neurocognitive Profile of Children With Autism Spectrum Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hôpital le Vinatier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hôpital le Vinatier</source>
  <oversight_info>
    <has_dmc>Yes</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 Early start Denver model (Rogers, 2010; Dawson, 2010) is a developmental and behavioral&#xD;
      model that aim to enhance socio-comunicative abilities and also global development of&#xD;
      children with Autism spectrum disorder (ASD). The purpose of this study is to identify&#xD;
      changes in neurocognitive profile of children population with ASD receiving Early Start&#xD;
      Denver Model (ESDM) applied 12 hours per week in comparison to children receiving other&#xD;
      interventions. That is a study proposed to children with ASD and their families that&#xD;
      participate already to a randomized control study called IDEA registered on&#xD;
      clinicaltrials.gov NCT02608333.&#xD;
&#xD;
      the investigators hypothesized that ESDM would increase social cognition, reduce shifting&#xD;
      attention time and increase preference for unpredictable stimuli.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      IDEA is a multicenter (4 centers in France and 1 center in Belgium), randomized, controlled,&#xD;
      single blind trial using a modified Zelen design .It concerns children with ASD aged 15 to 36&#xD;
      months without severe neurological or physical disorder and living in the proximity of one&#xD;
      the early intervention units. After diagnostic, Children will be included in a longitudinal&#xD;
      cohort with the consent of the parents. Sixty children will be drawn lots among 180 children&#xD;
      of the cohort and will be included in an ESDM intervention with the consent of the parents.&#xD;
      Two groups will be compared: an experimental group of 60 children receiving 12 hours a week&#xD;
      of ESDM intervention delivered by trained therapists during 2 years and a control group of&#xD;
      120 children receiving typical heterogeneous 'as-usual' intervention proposed by&#xD;
      professionals and public services over the same period. In IDEA development of communication&#xD;
      and social interactions and global developmental of all the children will be measured at&#xD;
      different time points (at baseline (t0), after 1 year (t1), after 2 years( t2)) over the two&#xD;
      years through standardized tests such as Autism diagnostic observation Schedule (ADOS-2),&#xD;
      Mullen Scales of Early Learning (MSEL) and the Vineland Adaptive Behavior Scale (VABS-2).&#xD;
&#xD;
      Children will be included in this second study called IDEA-EYE with parents' consent. Then,&#xD;
      preference for biological motion and social scene, shifting attention time and preference for&#xD;
      sameness will be measure in both groups with an Eye-tracker Tobii TX 300 at t0,t1 and t2.&#xD;
      These measures will also be collected in a group of children without ASD at t0,t1 and t2.&#xD;
&#xD;
      the investigators expect, as primary criteria, a significant superior time spend on&#xD;
      biological motion in ESDM group versus control group after 2 years of treatment. the&#xD;
      investigators also expect a significant superior orientation toward eyes in complex social&#xD;
      scenes, an inferior shifting attention time and a superior preference for unpredictable&#xD;
      stimuli in ESDM group versus ASD control group after 2 years. the investigators also expect&#xD;
      that ESDM group would have time spend on biological motion, orientation toward eyes in&#xD;
      complex scenes, shifting attention time and preference for unpredictable stimuli comparable&#xD;
      to children without ASD after 2 years.&#xD;
&#xD;
      This study would allow better understanding of ESDM active principles.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    one inclusion and not others&#xD;
  </why_stopped>
  <start_date type="Actual">May 29, 2017</start_date>
  <completion_date type="Actual">March 25, 2022</completion_date>
  <primary_completion_date type="Actual">March 25, 2022</primary_completion_date>
  <phase>N/A</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>ESDM is a comprehensive relational, developmental and behavioral intervention. It's described in a manual for professional (Rogers et al, 2010).&#xD;
Children receive ESDM at minimum 12H per week by trained therapist. Therapist work in collaboration with parents (at home) and preschool or nursery.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The primary outcome will be the time spent on biological motion in the task of visual preference stimuli.</measure>
    <time_frame>2 years</time_frame>
    <description>2 different types of stimuli (dynamic biological or geometrical movements) are presented in parallel on each part of the screen alternatively (left and/ or right). Child sit at 60 cm from the screen of the Eye-tracker can look towards the one or the other one stimuli.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Average proximity from pattern eyes norm in complex social scene task</measure>
    <time_frame>2 years</time_frame>
    <description>A 3-minute cartoon is displayed on a Tobii TX 300 eye-tracker. Inspired by the concept of a heatmap, for each frame of the video &quot;normative&quot; gaze pattern distribution are created by employing kernel density distribution estimation on the raw gaze data of TD individuals (Botev et al., 2009). For each patient we then will calculate the &quot;distance&quot; of his/hers gaze coordinates from this &quot;norm&quot;. Thus we will obtain one measure per frame of Proximity from the &quot;norm&quot;, which will be then averaged for the duration of the video.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference of saccadic latencies between overlap and gap condition</measure>
    <time_frame>2 years</time_frame>
    <description>in a gap/ overlap paradigm displayed on the Tobii TX 300 eye-tracker screen, we will measure the difference of mean of saccadic latencies between the two conditions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time spent on unpredictable stimuli</measure>
    <time_frame>2 years</time_frame>
    <description>2 type of stimuli are presented on the Eye-tracker screen : one very predictable stimuli and unpredictable stimuli.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Autism Spectrum Disorder</condition>
  <arm_group>
    <arm_group_label>ESDM-12</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>an experimental group of 60 children receiving 12 hours a week of Early Start Denver Model (ESDM) intervention delivered by trained therapists during 2 years ESDM is a comprehensive relational, developmental and behavioral intervention.It's described in a manual for Professional and parents.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>a control group of 120 children receiving typical heterogeneous 'as-usual' intervention proposed by professionals and public services over the same period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Early Start Denver Model</intervention_name>
    <description>ESDM is a comprehensive relational, developmental and behavioral intervention. It's described in a manual for professional (Rogers et al, 2010).&#xD;
Children receive ESDM at minimum 12H per week by trained therapist. Therapist work in collaboration with parents (at home) and preschool or nursery.</description>
    <arm_group_label>ESDM-12</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>'as-usual' intervention</intervention_name>
    <description>a control group receiving typical heterogeneous 'as-usual' intervention proposed by professionals and public services over the same period.</description>
    <arm_group_label>Control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children 15 months to 36 months&#xD;
&#xD;
          -  Children with autism spectrum disorder (according to international criteria, ADI and&#xD;
             ADOS)&#xD;
&#xD;
          -  DQ at 30 at least at the Early Learning Mullen Scale&#xD;
&#xD;
          -  Family domiciled within 40 minutes of an early intervention unit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe neurological or physical disorder identified in the child or family that would&#xD;
             interfere with intervention&#xD;
&#xD;
          -  Unavailability of the family for regular monitoring of the child by the investigator&#xD;
             center&#xD;
&#xD;
          -  Child with a Rett Sd or Childhood disintegrative disorders&#xD;
&#xD;
          -  Visual problems or with eyes in general&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Months</minimum_age>
    <maximum_age>36 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GEOFFRAY Marie-Maude, PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Hospitalier le Vinatier</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hopital Vinatier</name>
      <address>
        <city>Bron</city>
        <zip>69678</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>March 25, 2022</last_update_submitted>
  <last_update_submitted_qc>March 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Autistic Disorder</mesh_term>
    <mesh_term>Autism Spectrum Disorder</mesh_term>
    <mesh_term>Child Development Disorders, Pervasive</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/NCT03254264
org study id: 2015-A00696-43
nct id: NCT03254264
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The Early start Denver model (Rogers, 2010; Dawson, 2010) is a developmental and behavioral
      model that aim to enhance socio-comunicative abilities and also global development of
      children with Autism spectrum disorder (ASD). The purpose of this study is to identify
      changes in neurocognitive profile of children population with ASD receiving Early Start
      Denver Model (ESDM) applied 12 hours per week in comparison to children receiving other
      interventions. That is a study proposed to children with ASD and their families that
      participate already to a randomized control study called IDEA registered on
      clinicaltrials.gov NCT02608333.

      the investigators hypothesized that ESDM would increase social cognition, reduce shifting
      attention time and increase preference for unpredictable stimuli.
IDEA is a multicenter (4 centers in France and 1 center in Belgium), randomized, controlled,
      single blind trial using a modified Zelen design .It concerns children with ASD aged 15 to 36
      months without severe neurological or physical disorder and living in the proximity of one
      the early intervention units. After diagnostic, Children will be included in a longitudinal
      cohort with the consent of the parents. Sixty children will be drawn lots among 180 children
      of the cohort and will be included in an ESDM intervention with the consent of the parents.
      Two groups will be compared: an experimental group of 60 children receiving 12 hours a week
      of ESDM intervention delivered by trained therapists during 2 years and a control group of
      120 children receiving typical heterogeneous 'as-usual' intervention proposed by
      professionals and public services over the same period. In IDEA development of communication
      and social interactions and global developmental of all the children will be measured at
      different time points (at baseline (t0), after 1 year (t1), after 2 years( t2)) over the two
      years through standardized tests such as Autism diagnostic observation Schedule (ADOS-2),
      Mullen Scales of Early Learning (MSEL) and the Vineland Adaptive Behavior Scale (VABS-2).

      Children will be included in this second study called IDEA-EYE with parents' consent. Then,
      preference for biological motion and social scene, shifting attention time and preference for
      sameness will be measure in both groups with an Eye-tracker Tobii TX 300 at t0,t1 and t2.
      These measures will also be collected in a group of children without ASD at t0,t1 and t2.

      the investigators expect, as primary criteria, a significant superior time spend on
      biological motion in ESDM group versus control group after 2 years of treatment. the
      investigators also expect a significant superior orientation toward eyes in complex social
      scenes, an inferior shifting attention time and a superior preference for unpredictable
      stimuli in ESDM group versus ASD control group after 2 years. the investigators also expect
      that ESDM group would have time spend on biological motion, orientation toward eyes in
      complex scenes, shifting attention time and preference for unpredictable stimuli comparable
      to children without ASD after 2 years.

      This study would allow better understanding of ESDM active principles.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: ESDM is a comprehensive relational, developmental and behavioral intervention. It's described in a manual for professional (Rogers et al, 2010).
Children receive ESDM at minimum 12H per week by trained therapist. Therapist work in collaboration with parents (at home) and preschool or nursery.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: The primary outcome will be the time spent on biological motion in the task of visual preference stimuli.
time frame: 2 years
description: 2 different types of stimuli (dynamic biological or geometrical movements) are presented in parallel on each part of the screen alternatively (left and/ or right). Child sit at 60 cm from the screen of the Eye-tracker can look towards the one or the other one stimuli.
measure: Average proximity from pattern eyes norm in complex social scene task
time frame: 2 years
description: A 3-minute cartoon is displayed on a Tobii TX 300 eye-tracker. Inspired by the concept of a heatmap, for each frame of the video "normative" gaze pattern distribution are created by employing kernel density distribution estimation on the raw gaze data of TD individuals (Botev et al., 2009). For each patient we then will calculate the "distance" of his/hers gaze coordinates from this "norm". Thus we will obtain one measure per frame of Proximity from the "norm", which will be then averaged for the duration of the video.
measure: Difference of saccadic latencies between overlap and gap condition
time frame: 2 years
description: in a gap/ overlap paradigm displayed on the Tobii TX 300 eye-tracker screen, we will measure the difference of mean of saccadic latencies between the two conditions.
measure: Time spent on unpredictable stimuli
time frame: 2 years
description: 2 type of stimuli are presented on the Eye-tracker screen : one very predictable stimuli and unpredictable stimuli.
arm group label: ESDM-12
arm group type: Experimental
description: an experimental group of 60 children receiving 12 hours a week of Early Start Denver Model (ESDM) intervention delivered by trained therapists during 2 years ESDM is a comprehensive relational, developmental and behavioral intervention.It's described in a manual for Professional and parents.
arm group label: Control group
arm group type: Active Comparator
description: a control group of 120 children receiving typical heterogeneous 'as-usual' intervention proposed by professionals and public services over the same period.
intervention type: Behavioral
intervention name: Early Start Denver Model
description: ESDM is a comprehensive relational, developmental and behavioral intervention. It's described in a manual for professional (Rogers et al, 2010).
Children receive ESDM at minimum 12H per week by trained therapist. Therapist work in collaboration with parents (at home) and preschool or nursery.
arm group label: ESDM-12
intervention type: Behavioral
intervention name: 'as-usual' intervention
description: a control group receiving typical heterogeneous 'as-usual' intervention proposed by professionals and public services over the same period.
arm group label: Control group
criteria: 
gender: All
minimum age: 15 Months
maximum age: 36 Months
healthy volunteers: Accepts Healthy Volunteers
last name: GEOFFRAY Marie-Maude, PHD
role: Principal Investigator
affiliation: Centre Hospitalier le Vinatier
facility: 
country: France
responsible party type: Sponsor
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder
mesh term: Child Development Disorders, Pervasive