<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/NCT01677663</url>
  </required_header>
  <id_info>
    <org_study_id>201103003RB</org_study_id>
    <nct_id>NCT01677663</nct_id>
  </id_info>
  <brief_title>Neuropsychopathological Study of Autism</brief_title>
  <official_title>Neuropsychopathological Study of Autism: From Clinical, Neurocognitive, to Genetic Studies and Animal Models</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Taiwan University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Autism or autism spectrum disorder (ASD) is a relatively common (0.3% in Taiwan),&#xD;
      multi-factorial, genetically and clinically heterogeneous, childhood-onset neurodevelopmental&#xD;
      disorder. Due to its high heritability and severe long-term impairment without available&#xD;
      laboratory diagnosis, effective prevention or treatment, this disastrous disease has been&#xD;
      prioritized for molecular genetic studies. Recent CNVs investigation to identify rare&#xD;
      variants and GWA study with endophenotype approaches are promising strategies to identify&#xD;
      common genetic variants. In addition to intermediate phenotypes such as head circumstance,&#xD;
      speech delay, social impairments and stereotyped behaviors, evidence has demonstrated that&#xD;
      neuropsychology and neuroimages may be useful endophenotypes for autism. Dlgap2, Fbxo25, and&#xD;
      Arhgef10 knoutout mice generated from our previous CNV results will be characterized.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The specific aims of the study aree:&#xD;
&#xD;
        1. To collect complete environmental, developmental, clinical, neuropsychological, and&#xD;
           genetic data of 350 probands with autism (800 in total, 450 from [96HD008]) and their&#xD;
           families;&#xD;
&#xD;
        2. To re-sequence promoter region, all the exons, and the 3'UTR region of the DLGAP2, CLN8,&#xD;
           ARHGEF10, FBXO25, and GABRB3 genes (one gene per year);&#xD;
&#xD;
        3. To conduct fine-mapping and replication studies for selected candidate genes from GWA&#xD;
           study[96HD008];&#xD;
&#xD;
        4. To validate social impairment and speech delay as intermediate phenotypes and the&#xD;
           executive functions as effective cognitive endophenotypes by first demonstrating the&#xD;
           differences in these measures among probands, their unaffected siblings and&#xD;
           neurotypicals, followed by different genetic risks (e.g., neurexin, neuroligin, CNTNAP2,&#xD;
           SHANK3, MET, PTEN, WNT2, FOXP2, DLGAP2, CLN8, ARHGEF10, FBXO25, and GABRB3);&#xD;
&#xD;
        5. To validate the structural and functional connectivity as effective imaging&#xD;
           endophenotypes by demonstrating the differences between probands with autism, their&#xD;
           siblings, and matched neurotypicals; and&#xD;
&#xD;
        6. To characterize the phenotypes of and to explore the possible function of other&#xD;
           autism-related genes found by using GWAS, and to explore the possible drug targets for&#xD;
           the treatment for Dlgap2, Fbxo25, and Arhgef10 mutant mice.&#xD;
&#xD;
      The investigators will recruit 350 probands with clinical diagnosis of autism confirmed by&#xD;
      the ADI-R and ADOS, and their families. The probands and their siblings will also be assessed&#xD;
      for other psychiatric disorders (K-SADS-E); autistic symptom dimensions (SRS, SCQ, CAST,&#xD;
      ABC), other behavioral symptoms (CBCL, SNAP-IV), and perinatal/environmental risk factors.&#xD;
      The direct tests include intelligence (CPM/SPM, WISC-III, WPPSI-R) and neuropsychological&#xD;
      tests (CPT, WCST, CANTAB). The parents will be assessed for DSM-IV psychiatric disorders&#xD;
      (ASRI-4) and autistic features (AQ, SRS). The investigators will collect blood samples from&#xD;
      all the subjects. Probands with previous CNVs findings (n = 20) and high-functioning autism&#xD;
      (n=30) will receive the MRI assessments (Diffusion Spectrum Imaging, resting-state fMRI) as&#xD;
      compared to 50 age-, sex-, and handedness-matched neurotypicals.&#xD;
&#xD;
      The investigators will (1) characterize the behavioral, structural, electrophysiological and&#xD;
      biochemical phenotypes of Dlgap2, and Arhgef10 mice at 4 weeks, 8 weeks, 12 weeks and 16&#xD;
      weeks of ages; (2) explore the possible function of other autism-related genes found by GWAS&#xD;
      analysis; and (3) explore the possible drug targets for the treatment of autism from KO mice.&#xD;
      While the potential target is recognized, existing compounds of this target can be tested.&#xD;
&#xD;
      The investigators anticipate to establishing a representative cohort of 800 patients with&#xD;
      autism and their families from this study and [96HD008] with comprehensive clinical and&#xD;
      genetic data. This well-characterized cohort will contribute to validation of intermediate&#xD;
      phenotypes and cognitive and imaging endophenotypes for autism in this study, and will be&#xD;
      used to search for rare variants by CNVs analysis and common variants by GWAS analysis in&#xD;
      future study, and will pave the way to have 2-3 lines of well-characterized transgenic animal&#xD;
      models of autism (e.g., Dlgap2). In addition, a wealth of data from this cohort will benefit&#xD;
      to current and future investigation on autism and will be the basis for future international&#xD;
      collaboration. The investigators also anticipated to publication of 20 SCI papers (4 per&#xD;
      year) and presentation of our work in peer-reviewed scientific conferences by more than 40&#xD;
      posters or oral communications.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2011</start_date>
  <completion_date type="Anticipated">July 2016</completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Family-Based</observational_model>
  </study_design_info>
  <enrollment type="Anticipated">350</enrollment>
  <condition>Autism</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>
        The sample will consist of 350 probands with ASD, aged 3-25.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  subjects have a clinical diagnosis of autistic disorder or Asperger disorder defined&#xD;
             by the DSM-IV and ICD-10;&#xD;
&#xD;
          -  their ages range from 3 to 25 when we conduct the study;&#xD;
&#xD;
          -  subjects have at least one biological parent;&#xD;
&#xD;
          -  both parents of the subjects are Han Chinese;&#xD;
&#xD;
          -  subjects and their biological parents (and siblings if any) consent to participate in&#xD;
             this study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  if they currently meet criteria or have a history of DSM-IV Schizophrenia,&#xD;
             Schizoaffective Disorder, or Organic Psychosis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>25 Years</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>
  <overall_contact>
    <last_name>Susan Shur-Fen Gau, MD, PhD</last_name>
    <phone>886-2-23123456</phone>
    <phone_ext>66802</phone_ext>
    <email>gaushufe@ntu.edu.tw</email>
  </overall_contact>
  <location>
    <facility>
      <name>National Taiwan Univeristy Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Susan Shur-Fen Gau, MD, PhD</last_name>
      <phone>886-2-23123456</phone>
      <phone_ext>66802</phone_ext>
      <email>gaushufe@ntu.edu.tw</email>
    </contact>
    <investigator>
      <last_name>Susan Shur-Fen Gau, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Wen-Mei Fu, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Chia-Hsiang Chen, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Wen-Yih Isaac Tseng, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Po-Hsiu Kuo, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>August 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2012</study_first_posted>
  <last_update_submitted>August 31, 2012</last_update_submitted>
  <last_update_submitted_qc>August 31, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 3, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Taiwan University Hospital</investigator_affiliation>
    <investigator_full_name>National Taiwan University Hospital</investigator_full_name>
    <investigator_title>Susan Shur-Fen Gau</investigator_title>
  </responsible_party>
  <keyword>autism</keyword>
  <keyword>clinical phenotypes</keyword>
  <keyword>neuropsychology</keyword>
  <keyword>imaging endophenotypes</keyword>
  <keyword>family-based cohort</keyword>
  <keyword>knoutout mice</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Autistic 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/NCT01677663
org study id: 201103003RB
nct id: NCT01677663
lead sponsor: 
collaborator: 
has dmc: Yes
Autism or autism spectrum disorder (ASD) is a relatively common (0.3% in Taiwan),
      multi-factorial, genetically and clinically heterogeneous, childhood-onset neurodevelopmental
      disorder. Due to its high heritability and severe long-term impairment without available
      laboratory diagnosis, effective prevention or treatment, this disastrous disease has been
      prioritized for molecular genetic studies. Recent CNVs investigation to identify rare
      variants and GWA study with endophenotype approaches are promising strategies to identify
      common genetic variants. In addition to intermediate phenotypes such as head circumstance,
      speech delay, social impairments and stereotyped behaviors, evidence has demonstrated that
      neuropsychology and neuroimages may be useful endophenotypes for autism. Dlgap2, Fbxo25, and
      Arhgef10 knoutout mice generated from our previous CNV results will be characterized.
The specific aims of the study aree:

        1. To collect complete environmental, developmental, clinical, neuropsychological, and
           genetic data of 350 probands with autism (800 in total, 450 from [96HD008]) and their
           families;

        2. To re-sequence promoter region, all the exons, and the 3'UTR region of the DLGAP2, CLN8,
           ARHGEF10, FBXO25, and GABRB3 genes (one gene per year);

        3. To conduct fine-mapping and replication studies for selected candidate genes from GWA
           study[96HD008];

        4. To validate social impairment and speech delay as intermediate phenotypes and the
           executive functions as effective cognitive endophenotypes by first demonstrating the
           differences in these measures among probands, their unaffected siblings and
           neurotypicals, followed by different genetic risks (e.g., neurexin, neuroligin, CNTNAP2,
           SHANK3, MET, PTEN, WNT2, FOXP2, DLGAP2, CLN8, ARHGEF10, FBXO25, and GABRB3);

        5. To validate the structural and functional connectivity as effective imaging
           endophenotypes by demonstrating the differences between probands with autism, their
           siblings, and matched neurotypicals; and

        6. To characterize the phenotypes of and to explore the possible function of other
           autism-related genes found by using GWAS, and to explore the possible drug targets for
           the treatment for Dlgap2, Fbxo25, and Arhgef10 mutant mice.

      The investigators will recruit 350 probands with clinical diagnosis of autism confirmed by
      the ADI-R and ADOS, and their families. The probands and their siblings will also be assessed
      for other psychiatric disorders (K-SADS-E); autistic symptom dimensions (SRS, SCQ, CAST,
      ABC), other behavioral symptoms (CBCL, SNAP-IV), and perinatal/environmental risk factors.
      The direct tests include intelligence (CPM/SPM, WISC-III, WPPSI-R) and neuropsychological
      tests (CPT, WCST, CANTAB). The parents will be assessed for DSM-IV psychiatric disorders
      (ASRI-4) and autistic features (AQ, SRS). The investigators will collect blood samples from
      all the subjects. Probands with previous CNVs findings (n = 20) and high-functioning autism
      (n=30) will receive the MRI assessments (Diffusion Spectrum Imaging, resting-state fMRI) as
      compared to 50 age-, sex-, and handedness-matched neurotypicals.

      The investigators will (1) characterize the behavioral, structural, electrophysiological and
      biochemical phenotypes of Dlgap2, and Arhgef10 mice at 4 weeks, 8 weeks, 12 weeks and 16
      weeks of ages; (2) explore the possible function of other autism-related genes found by GWAS
      analysis; and (3) explore the possible drug targets for the treatment of autism from KO mice.
      While the potential target is recognized, existing compounds of this target can be tested.

      The investigators anticipate to establishing a representative cohort of 800 patients with
      autism and their families from this study and [96HD008] with comprehensive clinical and
      genetic data. This well-characterized cohort will contribute to validation of intermediate
      phenotypes and cognitive and imaging endophenotypes for autism in this study, and will be
      used to search for rare variants by CNVs analysis and common variants by GWAS analysis in
      future study, and will pave the way to have 2-3 lines of well-characterized transgenic animal
      models of autism (e.g., Dlgap2). In addition, a wealth of data from this cohort will benefit
      to current and future investigation on autism and will be the basis for future international
      collaboration. The investigators also anticipated to publication of 20 SCI papers (4 per
      year) and presentation of our work in peer-reviewed scientific conferences by more than 40
      posters or oral communications.
observational model: Family-Based
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: 25 Years
healthy volunteers: No
last name: Susan Shur-Fen Gau, MD, PhD
role: Principal Investigator
affiliation: National Taiwan University Hospital & College of Medicine
last name: Susan Shur-Fen Gau, MD, PhD
phone: 886-2-23123456
phone ext: 66802
email: gaushufe@ntu.edu.tw
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: National Taiwan University Hospital
investigator full name: National Taiwan University Hospital
investigator title: Susan Shur-Fen Gau
mesh term: Autistic Disorder