<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/NCT01721720</url>
  </required_header>
  <id_info>
    <org_study_id>120202</org_study_id>
    <secondary_id>12-HG-0202</secondary_id>
    <nct_id>NCT01721720</nct_id>
  </id_info>
  <brief_title>Genetic, Brain Structure, and Environmental Effects on ADHD</brief_title>
  <official_title>The Neurobehavioral, Environmental and Genetic Factors Impacting the Clinical Course of Attention Deficit Hyperactivity Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Human Genome Research Institute (NHGRI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      - Attention deficit hyperactivity disorder (ADHD) is one of the most common and inheritable&#xD;
      of all neuropsychiatric disorders. It causes problems with attention and impulse control.&#xD;
      However, the genetic component of ADHD has not been fully studied, including how genes&#xD;
      interact with the environment. Researchers want to study children and adults who have ADHD.&#xD;
      They will look at how genetic, brain structure, and environmental factors affect ADHD in&#xD;
      children and adults.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      - To study genetic, brain structure, and environmental factors in ADHD in children and&#xD;
      adults.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      - Individuals at least 3 years of age who have ADHD.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be screened with a physical exam and medical history.&#xD;
&#xD;
        -  Participants will be interviewed about their ADHD. They will also complete behavior and&#xD;
           psychological tests. Parents or guardians will complete the tests along with&#xD;
           participants under 18 years of age.&#xD;
&#xD;
        -  Participants will provide saliva or blood samples.&#xD;
&#xD;
        -  Participants will also have imaging studies of the brain.&#xD;
&#xD;
        -  Participants under 25 years of age will return once a year to repeat the tests. Those&#xD;
           over 25 years of age will have only the one set of tests. Those who are starting&#xD;
           stimulant drugs and who are receiving behavioral treatment for the first time will also&#xD;
           have another set of tests 12 weeks after the start of treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OBJECTIVES:&#xD;
&#xD;
      This study aims to provide novel phenotypes for genomic studies into Attention- Deficit&#xD;
      Hyperactivity Disorder (ADHD), one of the most common and heritable of all neuropsychiatric&#xD;
      disorders. It proposes to split the disorder into neurobiologically more meaningful entities&#xD;
      by delineating subgroups based on neurobehavioral profiles. It will also explore factors that&#xD;
      impact clinical course, focusing on the neural effects of treatment and the role of the child&#xD;
      s social environment.&#xD;
&#xD;
      POPULATION AND DESIGN:&#xD;
&#xD;
      Using a prospective longitudinal design, a group of children and adolescents with ADHD will&#xD;
      be followed. Additionally, families that have several members affected by ADHD will be&#xD;
      recruited.&#xD;
&#xD;
      OUTCOMES:&#xD;
&#xD;
      The study will link the onset and clinical course of ADHD with genotype, brain structure and&#xD;
      function, behavior and the child s social environment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 9, 2012</start_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Brain MRI</measure>
    <time_frame>yearly or at the participant's availability</time_frame>
    <description>Trajectories of brain development</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>DNA collection, clinical interviews, social network information gathering</measure>
    <time_frame>yearly or at the participant's convenience</time_frame>
    <description>To explore the neural, genomic and socio-environmental factors that determine the course of ADHD</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">1091</enrollment>
  <condition>Attention Deficit Disorder With Hyperactivity</condition>
  <arm_group>
    <arm_group_label>Participants with and without ADHD</arm_group_label>
    <description>Participants with and without ADHD</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Children, adolescents, and adults with Attention Deficit Hyperactivity Disorder and healthy&#xD;
        controls. Some participants will be from families that have many individuals affected by&#xD;
        ADHD.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA FOR ALL PARTICIPANTS:&#xD;
&#xD;
        Three or more years of age with no upper limit for age at time of enrollment. The lower&#xD;
        limit of 3 years of age is chosen as it is difficult to diagnose ADHD below this age, but&#xD;
        the diagnosis can be reliably made from age 3 onwards. As this study examines the&#xD;
        developmental trajectories of ADHD into adulthood, no upper age limit has been set.&#xD;
&#xD;
        INCLUSION CRITERIA FOR CLINICAL POPULATIONS:&#xD;
&#xD;
        Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) defined&#xD;
        ADHD. The DSM-IV diagnosis of ADHD will be based on the Parent Diagnostic Interview for&#xD;
        Children and Adolescents in participants 18 years or age and younger and the&#xD;
&#xD;
        Structured clinical interview for the Diagnosis of DSM Disorders for participants above 18&#xD;
        years of age. We include all forms of ADHD in DSM-5 (i.e. combined, predominately&#xD;
        hyperactive/impulsive, predominately inattentive and other specified presentations). ADHD&#xD;
        is rarely found in isolation and comorbidity is common. Thus the protocol will include&#xD;
        individuals with ADHD and the&#xD;
&#xD;
        following disorders: oppositional defiant disorder, conduct disorder, anxiety disorders&#xD;
        (generalized anxiety, specific phobias), tic disorders, mood disorders (dysthymia,&#xD;
        depression); specific learning disabilities and disruptive mood dysregulation disorder.&#xD;
&#xD;
        We will also include families where there is a incidence of &gt;30% of ADHD in first, second&#xD;
        and third degree relatives. This level is chosen as it is well above the incidence rate of&#xD;
        ADHD in the general population (~5-7%). Additional inclusion criteria are families where&#xD;
        the proband has at least one sibling and only one or neither parent is affected.&#xD;
&#xD;
        In studying the acute effects of treatment we will include all participants with ADHD who&#xD;
        are starting psychostimulant medications for the first time (all psychostimulant&#xD;
        preparations are included). We will also include participants with ADHD who are receiving&#xD;
        behavioral&#xD;
&#xD;
        management for ADHD for the first time.&#xD;
&#xD;
        INCLUSIONS CRITERIA FOR THE FAMILY STUDY:&#xD;
&#xD;
        We will also include families where there is a incidence of &gt;30% of ADHD in first, second&#xD;
        and third degree relatives. This level is chosen as it is well above the incidence rate of&#xD;
        ADHD in the general population (~5-7%). Additional inclusion criteria are families where&#xD;
        the proband has at least one sibling and only one or neither parent is affected.&#xD;
&#xD;
        We have already identified families of our currently enrolled probands in which at least 4&#xD;
        other first, second or third degree relatives have a current diagnosis of ADHD or had this&#xD;
        diagnosis in childhood (and have a similar number of unaffected relatives). We will recruit&#xD;
        further families with a similar density of individual affected by ADHD.&#xD;
&#xD;
        EXCLUSION CRITERIA FOR ALL PARTICIPANTS:&#xD;
&#xD;
        Full scale IQ of less than 70. Below this level a child is considered to have global&#xD;
        intellectual disability (classified in DSM-IVR as mental retardation). By definition this&#xD;
        means the individual cannot be considered to be a healthy control . While many individual&#xD;
        with IQ below 70 have symptoms of ADHD, the diagnosis is complicated by problems in&#xD;
        assessing attentional abilities.&#xD;
&#xD;
        Finally, there are often issues around the ability to give informed consent in adults with&#xD;
        global intellectual disability.&#xD;
&#xD;
        Birth before 32 weeks of gestation. Premature birth can have a profound effect on brain&#xD;
        function and structure.&#xD;
&#xD;
        Presence or history of medical conditions known to affect cerebral anatomy (eg epilepsy,&#xD;
        history of stroke). Genetic syndromes which are associated with well-established&#xD;
        alterations of gross cerebral structure- such as NF1, tuberous sclerosis and some forms of&#xD;
        epilepsy. Children with known microdeletion syndromes will not be excluded provided (1) the&#xD;
        syndrome is not known to be associated with alteration of cerebral anatomy (detectable on&#xD;
        current clinical MRI sequences) and (2) other exclusionary criteria do not apply such as&#xD;
        global intellectual impairment (defined in this protocol as IQ above 70). Data from these&#xD;
        individuals with microdeletion syndromes will&#xD;
&#xD;
        not however be included in GWAS due to analytic complications.&#xD;
&#xD;
        Dental braces (as these distort the MRI image). Metal in the body or other&#xD;
        contraindications for MRI scanning. For females who have reached menarche and have not yet&#xD;
        past menopause: pregnancy or inability or unwillingness to undergo pregnancy testing (for&#xD;
        MRI&#xD;
&#xD;
        safety).&#xD;
&#xD;
        For participants 60 years or older. Folstein mini mental state examination score of 26 or&#xD;
        greater. This is a widely accepted screening test for dementia.&#xD;
&#xD;
        ADDITIONAL EXCLUSION CRITERIA FOR HEALTHY VOLUNTEERS ONLY: Presence of any DSM-IV&#xD;
        psychiatric disorder in the subject or current use of psychiatric medication.&#xD;
&#xD;
        ADDITIONAL EXCLUSION CRITERIA FOR THE CLINICAL POPULATION ONLY:&#xD;
&#xD;
        Some neuropsychiatric disorders are either so rare or associated with such profound&#xD;
        alterations of brains structure and function that they will be excluded. This includes&#xD;
        psychotic disorders (including schizophrenia, psychosis NOS) bipolar affective disorder;&#xD;
        autism, substance dependence; dementia.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wallace P Shaw, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Human Genome Research Institute (NHGRI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2012-HG-0202.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>August 31, 2023</verification_date>
  <study_first_submitted>November 2, 2012</study_first_submitted>
  <study_first_submitted_qc>November 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 6, 2012</study_first_posted>
  <last_update_submitted>September 2, 2023</last_update_submitted>
  <last_update_submitted_qc>September 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Peer and Family Networks</keyword>
  <keyword>Longitudinal Outcome</keyword>
  <keyword>MRI Imaging</keyword>
  <keyword>Genetics</keyword>
  <keyword>Childhood Psychiatric Disorders</keyword>
  <keyword>Natural History</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>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>.All de-identified medical information will be placed in a NIH repository (e.g., Biomedical Translational Research Information System (BTRIS)) in accordance to NIH policies. We will also share genomic and phenotypic data in controlled access databases such as dbGAP (database of Genotypes and Phenotypes). Other databases may be used as approved by NIH for the sharing of de-identified data.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>The timeline for data sharing will follow the NHGRI Genomic Data Sharing Policy. Currently data is deposited following IRB review once the study data collection is complete and the data has undergone quality control steps.</ipd_time_frame>
    <ipd_access_criteria>Access requests for specific research purposes using NIH controlled-access data are reviewed by NIH Data Access Committees (DACs).</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT01721720
org study id: 120202
secondary id: 12-HG-0202
nct id: NCT01721720
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Background:

      - Attention deficit hyperactivity disorder (ADHD) is one of the most common and inheritable
      of all neuropsychiatric disorders. It causes problems with attention and impulse control.
      However, the genetic component of ADHD has not been fully studied, including how genes
      interact with the environment. Researchers want to study children and adults who have ADHD.
      They will look at how genetic, brain structure, and environmental factors affect ADHD in
      children and adults.

      Objectives:

      - To study genetic, brain structure, and environmental factors in ADHD in children and
      adults.

      Eligibility:

      - Individuals at least 3 years of age who have ADHD.

      Design:

        -  Participants will be screened with a physical exam and medical history.

        -  Participants will be interviewed about their ADHD. They will also complete behavior and
           psychological tests. Parents or guardians will complete the tests along with
           participants under 18 years of age.

        -  Participants will provide saliva or blood samples.

        -  Participants will also have imaging studies of the brain.

        -  Participants under 25 years of age will return once a year to repeat the tests. Those
           over 25 years of age will have only the one set of tests. Those who are starting
           stimulant drugs and who are receiving behavioral treatment for the first time will also
           have another set of tests 12 weeks after the start of treatment.
OBJECTIVES:

      This study aims to provide novel phenotypes for genomic studies into Attention- Deficit
      Hyperactivity Disorder (ADHD), one of the most common and heritable of all neuropsychiatric
      disorders. It proposes to split the disorder into neurobiologically more meaningful entities
      by delineating subgroups based on neurobehavioral profiles. It will also explore factors that
      impact clinical course, focusing on the neural effects of treatment and the role of the child
      s social environment.

      POPULATION AND DESIGN:

      Using a prospective longitudinal design, a group of children and adolescents with ADHD will
      be followed. Additionally, families that have several members affected by ADHD will be
      recruited.

      OUTCOMES:

      The study will link the onset and clinical course of ADHD with genotype, brain structure and
      function, behavior and the child s social environment.
observational model: Cohort
time perspective: Prospective
measure: Brain MRI
time frame: yearly or at the participant's availability
description: Trajectories of brain development
measure: DNA collection, clinical interviews, social network information gathering
time frame: yearly or at the participant's convenience
description: To explore the neural, genomic and socio-environmental factors that determine the course of ADHD
arm group label: Participants with and without ADHD
description: Participants with and without ADHD
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 3 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Wallace P Shaw, M.D.
role: Principal Investigator
affiliation: National Human Genome Research Institute (NHGRI)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2012-HG-0202.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Sponsor
mesh term: Hyperkinesis
mesh term: Attention Deficit Disorder with Hyperactivity
sharing ipd: Yes
ipd description: .All de-identified medical information will be placed in a NIH repository (e.g., Biomedical Translational Research Information System (BTRIS)) in accordance to NIH policies. We will also share genomic and phenotypic data in controlled access databases such as dbGAP (database of Genotypes and Phenotypes). Other databases may be used as approved by NIH for the sharing of de-identified data.
ipd info type: Study Protocol
ipd time frame: The timeline for data sharing will follow the NHGRI Genomic Data Sharing Policy. Currently data is deposited following IRB review once the study data collection is complete and the data has undergone quality control steps.
ipd access criteria: Access requests for specific research purposes using NIH controlled-access data are reviewed by NIH Data Access Committees (DACs).