<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/NCT01682915</url>
  </required_header>
  <id_info>
    <org_study_id>201204071RIC</org_study_id>
    <nct_id>NCT01682915</nct_id>
  </id_info>
  <brief_title>Structural and Functional Connectivity of Frontostriatal and Frontoparietal Networks as Endophenotypes of ADHD</brief_title>
  <official_title>Structural and Functional Connectivity of Frontostriatal and Frontoparietal Networks as Endophenotypes of Attention-deficit Hyperactivity 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>
      Attention deficit/hyperactivity disorder (ADHD) is a common, impairing, clinically and&#xD;
      genetically heterogeneous neuropsychiatric disorder with lifelong executive dysfunctions. The&#xD;
      ultimate goal of this 3-year case-control imaging genomic study with unaffected siblings and&#xD;
      typically developing (TD) children as controls is to identify useful imaging endophenotype&#xD;
      for ADHD by investigating the structural connectivity, as assessed by diffusion spectrum&#xD;
      imaging (DSI), and functional connectivity, as assessed by resting-state fMRI (rsfMRI) of&#xD;
      brain regions related to cognitive/executive controls with regards to the ADHD status and the&#xD;
      presence of dopamine transporter gene variants (DAT1).&#xD;
&#xD;
      Specific Aims:&#xD;
&#xD;
        1. to validate the executive functions, visuospatial memory, and structural and functional&#xD;
           connectivity in frontostriatal, and frontoparietal circuitries as effective&#xD;
           neurocognitive endophenotypes;&#xD;
&#xD;
        2. to correlate the data from structural and functional connectivity, neuropsychology, and&#xD;
           ADHD core symptoms stratifying by the presence of ADHD, proband-unaffected sibling&#xD;
           dyads, and the presence of DAT1 variant; and&#xD;
&#xD;
        3. To investigate reported candidate genes, in addition to DAT1 variant, related to&#xD;
           dopamine and noradrenergic neurotransmitter systems in the association with&#xD;
           neurocognitive endophenotypes such as DRD1, DRD2, DRD4, DRD5, DBH, MAO-A, ADRA2A,&#xD;
           ADRA2C, NET, and COMT.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The sample (n=240, 8 groups, ages 10-20, IQ &gt; 80) consists of (1) 30 ADHD probands with DAT1&#xD;
      variants, (2) 30 same-sex unaffected siblings, (3) 30 ADHD probands without DAT1 gene&#xD;
      variants, who were age-, sex-, and IQ-matched to Group 1, (4) 30 same-sex unaffected siblings&#xD;
      of Group 3, (5) 30 age-, sex- and IQ-matched TD controls for each of 4 groups (Groups 1, 2, 3&#xD;
      &amp; 4).&#xD;
&#xD;
      The assessments include psychiatric interviews, self-administered questionnaires (CBCL and&#xD;
      SNAP-IV for ADHD and behavioral problems; the SAICA for school and social function),&#xD;
      neurocognitive assessments (WISC-III-R or WAIS-III for intelligence, Conner's CPT for&#xD;
      sustained attention, inhibition, and vigilance, CANTAB for executive functions and&#xD;
      visuo-spatial memory), and MRI assessments (Structural MRI, DSI and rsfMRI).&#xD;
&#xD;
      Brain Imaging: (1) Structural MRI (T1- and T2-weighted images), DSI and rsfMRI data will be&#xD;
      acquired on a 3T MRI system with a 32-channel head coil. DSI employs a pulsed-gradient&#xD;
      spin-echo echo planar imaging (EPI) sequence by applying 102 diffusion gradient vectors and&#xD;
      the maximum diffusion sensitivity = 4000 s/mm2, and rsfMRI is a 6-minute scan using a&#xD;
      gradient-echo EPI sequence with 180 volumes. (2) Structural connectivity analysis: DSI&#xD;
      tractography will be performed using in-house software (DSI studio,&#xD;
      http://dsi-studio.labsolver.org/Home). Tracts-of-interest in the frontostriatal circuit and&#xD;
      the frontoparietal circuit will be identified, and tract-specific analysis will be used to&#xD;
      analyze the microstructural integrity along individual tract bundles. (3) Functional&#xD;
      connectivity analysis: SPM8 program and in-house MATLAB codes will be used for analyses of&#xD;
      rsfMRI data. Region-of-interests (ROIs) will be placed in the nodes of the corresponding&#xD;
      circuits according to an anatomical template (WFU_PickAtlas 3.03). These ROIs will serve for&#xD;
      tract determination in the tractography procedure and for seed regions in which BOLD signals&#xD;
      are extracted for regression analysis among nodes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2012</start_date>
  <completion_date type="Actual">July 31, 2015</completion_date>
  <primary_completion_date type="Actual">July 31, 2015</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>
  <number_of_groups>5</number_of_groups>
  <enrollment type="Actual">240</enrollment>
  <condition>Attention Deficit/Hyperactivity Disorder</condition>
  <arm_group>
    <arm_group_label>Group 1: ADHD+DAT1, Probands</arm_group_label>
    <description>30 ADHD probands with DAT1 variants</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2: ADHD+DAT1, Unaffected sibling</arm_group_label>
    <description>30 same-sex unaffected siblings of Group 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3: ADHD Drug-naïve, Probands</arm_group_label>
    <description>30 ADHD probands without DAT1 gene variants, who were age-, sex-, and IQ-matched to Group 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4: ADHD Drug-naïve, unaffected sibling</arm_group_label>
    <description>30 same-sex unaffected siblings of Group 3</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Matched controls</arm_group_label>
    <description>30 age-, sex- and IQ-matched TD controls for each of 4 groups</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        The sample (n=240, 8 groups, ages 10-20, IQ &gt; 80) consists of (1) 30 ADHD probands with&#xD;
        DAT1 variants, (2) 30 same-sex unaffected siblings, (3) 30 ADHD probands without DAT1 gene&#xD;
        variants, who were age-, sex-, and IQ-matched to Group 1, (4) 30 same-sex unaffected&#xD;
        siblings of Group 3, (5) 30 age-, sex- and IQ-matched TD controls for each of 4 groups&#xD;
        (Groups 1, 2, 3 &amp; 4).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ADHD+DAT1 groups: Subjects aged 12-20, who have clinical diagnosis of ADHD according&#xD;
             to the DSM-IV diagnostic criteria and who have risk alleles of DAT1 gene, regardless&#xD;
             of having same-sex unaffected siblings or the drug-naïve status.&#xD;
&#xD;
          -  ADHD drug-naïve groups: Subjects aged 12-20, who have clinical diagnosis of ADHD&#xD;
             according to the DSM-IV diagnostic criteria, who do not have risk alleles of DAT1&#xD;
             gene, who have the same-sex unaffected siblings and who have never been treated by&#xD;
             medication for treating ADHD.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  These subjects will be excluded from the study if they have any of the following&#xD;
             criteria: (1) Comorbidity with DSM-IV-TR diagnosis of pervasive developmental&#xD;
             disorder, schizophrenia, schizoaffective disorder, delusional disorder, other&#xD;
             psychotic disorder, organic psychosis, schizotypal personality disorder, bipolar&#xD;
             disorder, depression, severe anxiety disorders or substance use; (2) With&#xD;
             neurodegenerative disorder, epilepsy, involuntary movement disorder, congenital&#xD;
             metabolic disorder, brain tumor, history of severe head trauma, and history of&#xD;
             craniotomy; (3)With visual or hearing impairments, or motor disability which may&#xD;
             influence the process of MRI assessment; and (4) Full-scale IQ lower than 80. In&#xD;
             addition, if the control subjects have ODD or CD, they will be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>20 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <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>September 7, 2012</study_first_submitted>
  <study_first_submitted_qc>September 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2012</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 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Taiwan University Hospital</investigator_affiliation>
    <investigator_full_name>Statistical Center, NTUHCTC</investigator_full_name>
    <investigator_title>Susan Shur-Fen Gau</investigator_title>
  </responsible_party>
  <keyword>ADHD</keyword>
  <keyword>endophenotype</keyword>
  <keyword>executive function</keyword>
  <keyword>diffusion spectrum imaging</keyword>
  <keyword>resting-state fMRI</keyword>
  <keyword>frontostriatal and frontoparietal circuitries</keyword>
  <keyword>DAT1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperkinesis</mesh_term>
    <mesh_term>Attention Deficit Disorder with Hyperactivity</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/NCT01682915
org study id: 201204071RIC
nct id: NCT01682915
lead sponsor: 
has dmc: Yes
Attention deficit/hyperactivity disorder (ADHD) is a common, impairing, clinically and
      genetically heterogeneous neuropsychiatric disorder with lifelong executive dysfunctions. The
      ultimate goal of this 3-year case-control imaging genomic study with unaffected siblings and
      typically developing (TD) children as controls is to identify useful imaging endophenotype
      for ADHD by investigating the structural connectivity, as assessed by diffusion spectrum
      imaging (DSI), and functional connectivity, as assessed by resting-state fMRI (rsfMRI) of
      brain regions related to cognitive/executive controls with regards to the ADHD status and the
      presence of dopamine transporter gene variants (DAT1).

      Specific Aims:

        1. to validate the executive functions, visuospatial memory, and structural and functional
           connectivity in frontostriatal, and frontoparietal circuitries as effective
           neurocognitive endophenotypes;

        2. to correlate the data from structural and functional connectivity, neuropsychology, and
           ADHD core symptoms stratifying by the presence of ADHD, proband-unaffected sibling
           dyads, and the presence of DAT1 variant; and

        3. To investigate reported candidate genes, in addition to DAT1 variant, related to
           dopamine and noradrenergic neurotransmitter systems in the association with
           neurocognitive endophenotypes such as DRD1, DRD2, DRD4, DRD5, DBH, MAO-A, ADRA2A,
           ADRA2C, NET, and COMT.
The sample (n=240, 8 groups, ages 10-20, IQ > 80) consists of (1) 30 ADHD probands with DAT1
      variants, (2) 30 same-sex unaffected siblings, (3) 30 ADHD probands without DAT1 gene
      variants, who were age-, sex-, and IQ-matched to Group 1, (4) 30 same-sex unaffected siblings
      of Group 3, (5) 30 age-, sex- and IQ-matched TD controls for each of 4 groups (Groups 1, 2, 3
      & 4).

      The assessments include psychiatric interviews, self-administered questionnaires (CBCL and
      SNAP-IV for ADHD and behavioral problems; the SAICA for school and social function),
      neurocognitive assessments (WISC-III-R or WAIS-III for intelligence, Conner's CPT for
      sustained attention, inhibition, and vigilance, CANTAB for executive functions and
      visuo-spatial memory), and MRI assessments (Structural MRI, DSI and rsfMRI).

      Brain Imaging: (1) Structural MRI (T1- and T2-weighted images), DSI and rsfMRI data will be
      acquired on a 3T MRI system with a 32-channel head coil. DSI employs a pulsed-gradient
      spin-echo echo planar imaging (EPI) sequence by applying 102 diffusion gradient vectors and
      the maximum diffusion sensitivity = 4000 s/mm2, and rsfMRI is a 6-minute scan using a
      gradient-echo EPI sequence with 180 volumes. (2) Structural connectivity analysis: DSI
      tractography will be performed using in-house software (DSI studio,
      http://dsi-studio.labsolver.org/Home). Tracts-of-interest in the frontostriatal circuit and
      the frontoparietal circuit will be identified, and tract-specific analysis will be used to
      analyze the microstructural integrity along individual tract bundles. (3) Functional
      connectivity analysis: SPM8 program and in-house MATLAB codes will be used for analyses of
      rsfMRI data. Region-of-interests (ROIs) will be placed in the nodes of the corresponding
      circuits according to an anatomical template (WFU_PickAtlas 3.03). These ROIs will serve for
      tract determination in the tractography procedure and for seed regions in which BOLD signals
      are extracted for regression analysis among nodes.
observational model: Other
time perspective: Other
arm group label: Group 1: ADHD+DAT1, Probands
description: 30 ADHD probands with DAT1 variants
arm group label: Group 2: ADHD+DAT1, Unaffected sibling
description: 30 same-sex unaffected siblings of Group 1
arm group label: Group 3: ADHD Drug-naïve, Probands
description: 30 ADHD probands without DAT1 gene variants, who were age-, sex-, and IQ-matched to Group 1
arm group label: Group 4: ADHD Drug-naïve, unaffected sibling
description: 30 same-sex unaffected siblings of Group 3
arm group label: Matched controls
description: 30 age-, sex- and IQ-matched TD controls for each of 4 groups
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 12 Years
maximum age: 20 Years
healthy volunteers: No
facility: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: National Taiwan University Hospital
investigator full name: Statistical Center, NTUHCTC
investigator title: Susan Shur-Fen Gau
mesh term: Hyperkinesis
mesh term: Attention Deficit Disorder with Hyperactivity