<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/NCT02228876</url>
  </required_header>
  <id_info>
    <org_study_id>201403019RINA</org_study_id>
    <nct_id>NCT02228876</nct_id>
  </id_info>
  <brief_title>A Family Study of Copy Number Variations in Patients With Autism Spectrum Disorder</brief_title>
  <official_title>A Family Study of Copy Number Variations in Patients With Autism Spectrum Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This 3-year proposal is a family-based cohort study to establish a representative sample of&#xD;
      probands with ASD and their parents with well-characterized environmental, clinical&#xD;
      phenotypes, endophenotypes, and genetic data to conduct CNV experiments and the&#xD;
      genotype-phenotype correlations. Based on our previous findings, probands with CNVs larger&#xD;
      than 500kb has been identified and their families will be newly recruit in the present&#xD;
      project to reveal the origin of the CNVs and reveal the clinical feature of the families. The&#xD;
      significant findings in specific genes will conduct pathway analysis to reveal the etiology&#xD;
      in ASD, providing further understanding in the disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Due to its high prevalence, long-term impairment, high genetic component (heritability &gt;&#xD;
      90%), and lack of effective prevention and treatment, ASD has been prioritized for genetic&#xD;
      studies. However, despite extensive genetic research, there has been no any conclusive result&#xD;
      mainly due to the clinical and genetic heterogeneity of ASD. Given the progress of CNV study&#xD;
      in ASD, several challenges remain to be faced with, such as differences in phenotypic&#xD;
      definition across different studies; a lack of population norms for CNVs, and a lack of&#xD;
      consensus in methods for CNV detection and analysis. In the present study, the large segments&#xD;
      of CNV found in ASD probands will be compared with standardized controls from National Center&#xD;
      for Genome Medicine (NCGM), Academia Sinica to identify the possible CNVs. The other&#xD;
      important issue of CNV research in ASD is to investigate whether the origin of CNVs are&#xD;
      inherited or de novo. By collecting the complete background and revealing the CNVs of the&#xD;
      parents and siblings, the origin of the CNVs will be uncovered in the present project. The&#xD;
      candidate genes from important CNVs will be identified by pathway analysis. Gene expression&#xD;
      will be conducted to confirm the pathogenic genes. Notably the present study will help bridge&#xD;
      the gap to translate the bench findings to bedside to help early detection of ASD and pave&#xD;
      the way developing effective treatment for ASD in the future.&#xD;
&#xD;
      Specific Aims:&#xD;
&#xD;
      With the above-mentioned rationale of this project and limited research budget from NSC, the&#xD;
      ultimate goal of this project is to identify the important CNVs to reveal the pathogenic&#xD;
      genes for ASD for future translational research in ASD and to prospectively characterize&#xD;
      clinical features of ASD individuals with CNV.&#xD;
&#xD;
      The specific aims of this study are as follows,&#xD;
&#xD;
        1. To identify important and pathogenic CNVs by comparing the CNVs and CNPs of the controls&#xD;
           provided by NCGM , Academia Sinica;&#xD;
&#xD;
        2. To assess parents and siblings of ASD patients who were found to have ~500 kb CNVs in&#xD;
           our previous study using clinical, psychopathological, and social measures for family&#xD;
           study and also to conduct CNV analysis in the families to determine the origin of the&#xD;
           CNVs;&#xD;
&#xD;
        3. To conduct a follow-up assessments of clinical features, and social and&#xD;
           neuropsychological functions of ASD probands with CNV to examine the phenotype changes&#xD;
           over time;&#xD;
&#xD;
        4. To study the clinical phenotypes between de novo and inherited groups to reveal the&#xD;
           pathogenic CNVs;&#xD;
&#xD;
        5. To conduct pathway analysis of genes involved in the CNVs, and to confirm the pathogenic&#xD;
           genes by conducting gene expression analysis;&#xD;
&#xD;
        6. To investigate the associations of clinical phenotypes such as autistic tendency, and&#xD;
           social impairments between (1) probands with/without CNVs/controls, and (2)&#xD;
           probands/unaffected siblings/controls.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2014</start_date>
  <completion_date type="Actual">July 31, 2017</completion_date>
  <primary_completion_date type="Actual">July 31, 2017</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>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Diagnosis of autism</measure>
    <time_frame>1 day</time_frame>
    <description>Using the Autism Diagnostic Interview-Revised (ADI-R) to assess the developmental and behavioral aspects of autism, including reciprocal social interaction, communication, and repetitive behaviors and stereotyped patterns</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Diagnosis of psychiatric disorders</measure>
    <time_frame>1 day</time_frame>
    <description>Using the Schedule for Affective Disorders &amp; Schizophrenia (K-SADS-E) to assess the DSM-IV diagnosis of ADHD and other psychiatric disorders</description>
  </secondary_outcome>
  <enrollment type="Actual">360</enrollment>
  <condition>Autism Spectrum Disorder</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      The subjects will receive blood withdrawal. The blood sample will be used for establishing&#xD;
      lymphoblastoid cell lines, which will be used for molecular genetic experiments.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Based on our preliminary CNV results of 339 probands, approximately 120 probands had been&#xD;
        identified to have CNVs larger than 500kb. In the present project, the parents and siblings&#xD;
        of the probands with CNVs larger than 500kb will be recruited (estimated sample size,&#xD;
        parents = 200, siblings = 40) and reassess the ~120 probands.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. subjects have a clinical diagnosis of autistic disorder or Asperger disorder defined&#xD;
             by the DSM-IV and ICD-10 criteria and ASD defined by the DSM-5, which was made by&#xD;
             board-certificated child psychiatrists at the first visit and following visits;&#xD;
&#xD;
          2. their ages range from 3 to 30;&#xD;
&#xD;
          3. subjects have at least one biological parent;&#xD;
&#xD;
          4. both parents are Han Chinese; and&#xD;
&#xD;
          5. subjects and their biological parents consent to participate in this study for&#xD;
             complete phenotype assessments and blood withdraw for genetic study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  if they currently meet criteria or have a history of the following condition as&#xD;
             defined by DSM-IV: Schizophrenia, Schizoaffective Disorder, or Organic Psychosis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Susan Shur-Fen Gau, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital &amp; College of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Taiwan Univeristy Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2014</study_first_posted>
  <last_update_submitted>September 1, 2021</last_update_submitted>
  <last_update_submitted_qc>September 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2021</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/NCT02228876
org study id: 201403019RINA
nct id: NCT02228876
lead sponsor: 
has dmc: Yes
This 3-year proposal is a family-based cohort study to establish a representative sample of
      probands with ASD and their parents with well-characterized environmental, clinical
      phenotypes, endophenotypes, and genetic data to conduct CNV experiments and the
      genotype-phenotype correlations. Based on our previous findings, probands with CNVs larger
      than 500kb has been identified and their families will be newly recruit in the present
      project to reveal the origin of the CNVs and reveal the clinical feature of the families. The
      significant findings in specific genes will conduct pathway analysis to reveal the etiology
      in ASD, providing further understanding in the disease.
Due to its high prevalence, long-term impairment, high genetic component (heritability >
      90%), and lack of effective prevention and treatment, ASD has been prioritized for genetic
      studies. However, despite extensive genetic research, there has been no any conclusive result
      mainly due to the clinical and genetic heterogeneity of ASD. Given the progress of CNV study
      in ASD, several challenges remain to be faced with, such as differences in phenotypic
      definition across different studies; a lack of population norms for CNVs, and a lack of
      consensus in methods for CNV detection and analysis. In the present study, the large segments
      of CNV found in ASD probands will be compared with standardized controls from National Center
      for Genome Medicine (NCGM), Academia Sinica to identify the possible CNVs. The other
      important issue of CNV research in ASD is to investigate whether the origin of CNVs are
      inherited or de novo. By collecting the complete background and revealing the CNVs of the
      parents and siblings, the origin of the CNVs will be uncovered in the present project. The
      candidate genes from important CNVs will be identified by pathway analysis. Gene expression
      will be conducted to confirm the pathogenic genes. Notably the present study will help bridge
      the gap to translate the bench findings to bedside to help early detection of ASD and pave
      the way developing effective treatment for ASD in the future.

      Specific Aims:

      With the above-mentioned rationale of this project and limited research budget from NSC, the
      ultimate goal of this project is to identify the important CNVs to reveal the pathogenic
      genes for ASD for future translational research in ASD and to prospectively characterize
      clinical features of ASD individuals with CNV.

      The specific aims of this study are as follows,

        1. To identify important and pathogenic CNVs by comparing the CNVs and CNPs of the controls
           provided by NCGM , Academia Sinica;

        2. To assess parents and siblings of ASD patients who were found to have ~500 kb CNVs in
           our previous study using clinical, psychopathological, and social measures for family
           study and also to conduct CNV analysis in the families to determine the origin of the
           CNVs;

        3. To conduct a follow-up assessments of clinical features, and social and
           neuropsychological functions of ASD probands with CNV to examine the phenotype changes
           over time;

        4. To study the clinical phenotypes between de novo and inherited groups to reveal the
           pathogenic CNVs;

        5. To conduct pathway analysis of genes involved in the CNVs, and to confirm the pathogenic
           genes by conducting gene expression analysis;

        6. To investigate the associations of clinical phenotypes such as autistic tendency, and
           social impairments between (1) probands with/without CNVs/controls, and (2)
           probands/unaffected siblings/controls.
observational model: Other
time perspective: Other
measure: Diagnosis of autism
time frame: 1 day
description: Using the Autism Diagnostic Interview-Revised (ADI-R) to assess the developmental and behavioral aspects of autism, including reciprocal social interaction, communication, and repetitive behaviors and stereotyped patterns
measure: Diagnosis of psychiatric disorders
time frame: 1 day
description: Using the Schedule for Affective Disorders & Schizophrenia (K-SADS-E) to assess the DSM-IV diagnosis of ADHD and other psychiatric disorders
The subjects will receive blood withdrawal. The blood sample will be used for establishing
      lymphoblastoid cell lines, which will be used for molecular genetic experiments.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 3 Years
maximum age: N/A
healthy volunteers: No
last name: Susan Shur-Fen Gau, MD, PhD
role: Principal Investigator
affiliation: National Taiwan University Hospital & College of Medicine
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder
mesh term: Child Development Disorders, Pervasive