<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/NCT02200679</url>
  </required_header>
  <id_info>
    <org_study_id>201302002</org_study_id>
    <nct_id>NCT02200679</nct_id>
  </id_info>
  <brief_title>National Study on Autism Spectrum Disorder in China</brief_title>
  <official_title>Study on Approach and Standards for Diagnosis, Prevention and Control of Autism Spectrum Disorder in Children in China</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Health and Family Planning Commission, P.R.China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fudan University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aims of the national population-based study on Autism Spectrum Disorder (ASD) include:&#xD;
      (1) to understand the overall prevalence of ASD in children aged 6-12 years in 8 cities&#xD;
      (n=120,000), (2) to explore environmental and genetic risk factors associated with ASD&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is a multicenter, cross-sectional study involing eight cities. The program includes&#xD;
      a prevalence study and a risk factors analysis.&#xD;
&#xD;
        1. Prevalence study on ASD To estimate the national prevalence of ASD in Chinese pediatric&#xD;
           population aged 6-12 years.&#xD;
&#xD;
           1.1. Target population This 4-year study is initiated in the year of 2013 in eight&#xD;
           cities of China . For each city, 3 communities with different economic levels were&#xD;
           chosen including all children born within Jan 2001 to Dec 2007 (ages 6-12 years at&#xD;
           screening) with local residency or have lived in the community over 6 months. The ASD&#xD;
           children who are attending special education schools and meet with the inclusion&#xD;
           criteria will also be included in the prevalence estimation.&#xD;
&#xD;
           1.2. Sample size Based on the previous regional studies , we plan to recruit approx.15,&#xD;
           000 subjects for each city (average. 5,000 subjects for each community), and 120,000&#xD;
           subjects in total then comprise the national study sample. The plan will be updated,&#xD;
           based on the prevalence obtained in the pilot study.&#xD;
&#xD;
           1.3. Screening and diagnosis The screening tool will be chosen from Autism Spectrum&#xD;
           Rating Scale (ASRS) or SRS（Social Responsiveness Scale） after pilot study.The&#xD;
           questionnaire is a parent-administered form that takes approximately 15-20 minutes to&#xD;
           complete. Parents of recruied children were invited to complete the questionnaire.&#xD;
           Parents of all questionnaire screen-positive children will be contacted for appointing&#xD;
           further diagnostic evaluations. Children whose parents could not be reached are&#xD;
           classified as non-responders. The DSM-Ⅳ, ADI-R and ADOS (ADI-R: Autism Diagnosis&#xD;
           Interview-Revised, ADOS: Autism Diagnosis Observation Scales) are used for diagnostic&#xD;
           evaluations. Co-morbidities, such as epilepsy and ADHD (Attention Deficit Hyperactivity&#xD;
           Disorder )after aditional medical examinations such as, EEG(electroencephalogram), head&#xD;
           circumference, anthropometrics, allergies, sleep patterns, etc.&#xD;
&#xD;
        2. Risk Factors study on ASD A classic case-control design is applied to explore the risk&#xD;
           factors of ASD. 2.1. Study subjects 2.1.1. Cases and control Cases were children living&#xD;
           in target communities who are identified as positive based on questionnaire screen and&#xD;
           the subsequent diagnosis with DSM-Ⅳ, ADOS and ADI-R.&#xD;
&#xD;
      Controls were children who are screened to be negative and matched to cases by age, gender,&#xD;
      and class.&#xD;
&#xD;
      2.2. Environmental pollutants exposures Given the hypothesis that environmental factors might&#xD;
      play a role in the etiology of ASD, we will analyze the biological samples of the subjects to&#xD;
      investigate environmental exposures including chronic lead exposure, pesticides exposure, and&#xD;
      endocrine disruptors exposure , for which, hair, blood, and urine will be collected for cases&#xD;
      and controls. The detailed protocol for the measurement of each kind of biological sample has&#xD;
      been introduced everywhere (see the references in individual block).&#xD;
&#xD;
      2.3. Analysis of other potential risk factors This study will also analyze the association&#xD;
      between the onset of ASD and other risk factors, including diet (), living&#xD;
      environment(),perinatal characteristics of parents, feeding history, baby growth and&#xD;
      development after birth by using questionnaire and reviewing medical records.&#xD;
&#xD;
      2.4. Genetic analysis We are going to use the targeted area capture technology developed&#xD;
      before and HiSeq2000, the second generation of high throughput sequencing platform, to carry&#xD;
      out the molecular diagnosis screening (monogenic disease). Also, we will screen through Trio&#xD;
      those ASD-related genetic mutations that are of high credibility and occur frequently so as&#xD;
      to classify ASDs according to their definite etiologies.Furthermore, we will continue the&#xD;
      study on the distribution of ASD relevant gene mutations among patients in China, which will&#xD;
      lay a solid foundation for further studies of molecular epidemiology.Meanwhile, we will also&#xD;
      apply genome-wide sequencing technology on the positive cases so as to find new mutation that&#xD;
      might serve as potential molecular markers facilitating the diagnosis and treatment of ASDs.&#xD;
&#xD;
      A pilot study involving 4 cities (n=400 for each, in total n&gt;=1600)will be conducted to test&#xD;
      all methodology that will be applied in the prevalence study. A diagnostic study will be&#xD;
      performed to evalute the performance of ASRS and SRS in screening ASD, one of which will be&#xD;
      applied in the main study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2014</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>prevalence of autism spectrum disorder</measure>
    <time_frame>3-12 years</time_frame>
    <description>The outcome of the study include ASD and its commorbidities. The disease occurs in children as early as 18 months old, however the confirmation of diagnosis usually is 3 or later. 6-12 years is time frame for confirmed diagnosis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ASRS</measure>
    <time_frame>6-18 years</time_frame>
    <description>ASRS is a measure for screen ASD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ADI-R</measure>
    <time_frame>4-18 yeas</time_frame>
    <description>The ADI-R is a good diagnosis tool for children with ASD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ADOS</measure>
    <time_frame>14months-16 years</time_frame>
    <description>The ADOS is a appropriate instrutment for ASD diagnosis.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">143755</enrollment>
  <condition>Autism Spectrum Disorders</condition>
  <arm_group>
    <arm_group_label>Autism Spectrum Disorders</arm_group_label>
    <description>Cases were children living in target communities who are identified as positive based on questionnaire screen and the following diagnosis with DSM-Ⅳ, ADOS and ADI-R</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      whole blood 2*5ml, (isolate Plasma, Serum and white cell) Hair, Urine(biosample will be&#xD;
      collected only for Cases 1200 +Controls 1200)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Community-based populations aged 6-12 years old form 8 cities in China&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All children aged 6-12 years old and have lived in the recruied community over 6&#xD;
             months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  None&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yi Wang, PhD,MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital of Fudan University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Capital Institute of Pediatrics</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Chongqing Medical University</name>
      <address>
        <city>Chongqing</city>
        <state>Chongqing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Third Affiliated Hosptial,Sun Yat-Sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harbin Medical University</name>
      <address>
        <city>Harbin</city>
        <state>Heilongjiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central South University</name>
      <address>
        <city>ChangSha</city>
        <state>Hunan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chengdu Women's and Children's Central Hospital</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sichuan University</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The 2nd Affiliated Hospital of Wenzhou Medical University</name>
      <address>
        <city>Wenzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>http://ch.shmu.edu.cn/</url>
    <description>The Children's Hospital of Fudan University (CHFU) is a service of the National Institute on Children</description>
  </link>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <last_update_submitted>May 15, 2017</last_update_submitted>
  <last_update_submitted_qc>May 15, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 16, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fudan University</investigator_affiliation>
    <investigator_full_name>Yi Wang</investigator_full_name>
    <investigator_title>Vice Prsident Chlidren's Hospital of Fudan University</investigator_title>
  </responsible_party>
  <keyword>Autism spectrum disorders</keyword>
  <keyword>Prevalence</keyword>
  <keyword>Diagnosis</keyword>
  <keyword>Screen</keyword>
  <keyword>Risk Factor</keyword>
  <keyword>SRS</keyword>
  <keyword>ASRS</keyword>
  <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/NCT02200679
org study id: 201302002
nct id: NCT02200679
lead sponsor: 
collaborator: 
has dmc: Yes
The aims of the national population-based study on Autism Spectrum Disorder (ASD) include:
      (1) to understand the overall prevalence of ASD in children aged 6-12 years in 8 cities
      (n=120,000), (2) to explore environmental and genetic risk factors associated with ASD
The study is a multicenter, cross-sectional study involing eight cities. The program includes
      a prevalence study and a risk factors analysis.

        1. Prevalence study on ASD To estimate the national prevalence of ASD in Chinese pediatric
           population aged 6-12 years.

           1.1. Target population This 4-year study is initiated in the year of 2013 in eight
           cities of China . For each city, 3 communities with different economic levels were
           chosen including all children born within Jan 2001 to Dec 2007 (ages 6-12 years at
           screening) with local residency or have lived in the community over 6 months. The ASD
           children who are attending special education schools and meet with the inclusion
           criteria will also be included in the prevalence estimation.

           1.2. Sample size Based on the previous regional studies , we plan to recruit approx.15,
           000 subjects for each city (average. 5,000 subjects for each community), and 120,000
           subjects in total then comprise the national study sample. The plan will be updated,
           based on the prevalence obtained in the pilot study.

           1.3. Screening and diagnosis The screening tool will be chosen from Autism Spectrum
           Rating Scale (ASRS) or SRS（Social Responsiveness Scale） after pilot study.The
           questionnaire is a parent-administered form that takes approximately 15-20 minutes to
           complete. Parents of recruied children were invited to complete the questionnaire.
           Parents of all questionnaire screen-positive children will be contacted for appointing
           further diagnostic evaluations. Children whose parents could not be reached are
           classified as non-responders. The DSM-Ⅳ, ADI-R and ADOS (ADI-R: Autism Diagnosis
           Interview-Revised, ADOS: Autism Diagnosis Observation Scales) are used for diagnostic
           evaluations. Co-morbidities, such as epilepsy and ADHD (Attention Deficit Hyperactivity
           Disorder )after aditional medical examinations such as, EEG(electroencephalogram), head
           circumference, anthropometrics, allergies, sleep patterns, etc.

        2. Risk Factors study on ASD A classic case-control design is applied to explore the risk
           factors of ASD. 2.1. Study subjects 2.1.1. Cases and control Cases were children living
           in target communities who are identified as positive based on questionnaire screen and
           the subsequent diagnosis with DSM-Ⅳ, ADOS and ADI-R.

      Controls were children who are screened to be negative and matched to cases by age, gender,
      and class.

      2.2. Environmental pollutants exposures Given the hypothesis that environmental factors might
      play a role in the etiology of ASD, we will analyze the biological samples of the subjects to
      investigate environmental exposures including chronic lead exposure, pesticides exposure, and
      endocrine disruptors exposure , for which, hair, blood, and urine will be collected for cases
      and controls. The detailed protocol for the measurement of each kind of biological sample has
      been introduced everywhere (see the references in individual block).

      2.3. Analysis of other potential risk factors This study will also analyze the association
      between the onset of ASD and other risk factors, including diet (), living
      environment(),perinatal characteristics of parents, feeding history, baby growth and
      development after birth by using questionnaire and reviewing medical records.

      2.4. Genetic analysis We are going to use the targeted area capture technology developed
      before and HiSeq2000, the second generation of high throughput sequencing platform, to carry
      out the molecular diagnosis screening (monogenic disease). Also, we will screen through Trio
      those ASD-related genetic mutations that are of high credibility and occur frequently so as
      to classify ASDs according to their definite etiologies.Furthermore, we will continue the
      study on the distribution of ASD relevant gene mutations among patients in China, which will
      lay a solid foundation for further studies of molecular epidemiology.Meanwhile, we will also
      apply genome-wide sequencing technology on the positive cases so as to find new mutation that
      might serve as potential molecular markers facilitating the diagnosis and treatment of ASDs.

      A pilot study involving 4 cities (n=400 for each, in total n>=1600)will be conducted to test
      all methodology that will be applied in the prevalence study. A diagnostic study will be
      performed to evalute the performance of ASRS and SRS in screening ASD, one of which will be
      applied in the main study.
observational model: Other
time perspective: Cross-Sectional
measure: prevalence of autism spectrum disorder
time frame: 3-12 years
description: The outcome of the study include ASD and its commorbidities. The disease occurs in children as early as 18 months old, however the confirmation of diagnosis usually is 3 or later. 6-12 years is time frame for confirmed diagnosis.
measure: ASRS
time frame: 6-18 years
description: ASRS is a measure for screen ASD.
measure: ADI-R
time frame: 4-18 yeas
description: The ADI-R is a good diagnosis tool for children with ASD
measure: ADOS
time frame: 14months-16 years
description: The ADOS is a appropriate instrutment for ASD diagnosis.
arm group label: Autism Spectrum Disorders
description: Cases were children living in target communities who are identified as positive based on questionnaire screen and the following diagnosis with DSM-Ⅳ, ADOS and ADI-R
whole blood 2*5ml, (isolate Plasma, Serum and white cell) Hair, Urine(biosample will be
      collected only for Cases 1200 +Controls 1200)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Years
maximum age: 12 Years
healthy volunteers: No
last name: Yi Wang, PhD,MD
role: Principal Investigator
affiliation: Children's Hospital of Fudan University
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
url: http://ch.shmu.edu.cn/
description: The Children's Hospital of Fudan University (CHFU) is a service of the National Institute on Children
responsible party type: Principal Investigator
investigator affiliation: Fudan University
investigator full name: Yi Wang
investigator title: Vice Prsident Chlidren's Hospital of Fudan University
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder
mesh term: Child Development Disorders, Pervasive