<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/NCT01678209</url>
  </required_header>
  <id_info>
    <org_study_id>GCO 11-0161</org_study_id>
    <secondary_id>5R01MH095766-02</secondary_id>
    <nct_id>NCT01678209</nct_id>
  </id_info>
  <brief_title>Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach</brief_title>
  <official_title>Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Icahn School of Medicine at Mount Sinai</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Icahn School of Medicine at Mount Sinai</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The growing number of medications used to treat attention-deficit/hyperactivity disorder&#xD;
      (ADHD) raises important questions about whether different medications have similar or&#xD;
      different therapeutic mechanisms of action. We have recently shown that the stimulant&#xD;
      methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) produce clinical improvement&#xD;
      via a common mechanism in motor cortex, and distinct actions in frontostriatal and midline&#xD;
      cingulate-precuneus regions. These exciting findings offer a window into the common and&#xD;
      unique neurophysiological mechanisms of response to stimulant and non-stimulant treatments.&#xD;
      However, the interpretation and clinical utility of these results would be greatly enhanced&#xD;
      by in-depth investigation of the impact of the two treatments on relevant neural networks,&#xD;
      and analyses which evaluate whether improvement is achieved via normalization or other&#xD;
      adaptive changes in brain function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The specific aims of this project are to use functional magnetic resonance imaging (fMRI) to&#xD;
      determine the significance of activation changes over treatment related to clinical&#xD;
      improvement, and the impact of treatment on neural connectivity within and between the&#xD;
      anti-correlated frontostriatal 'task-positive' circuit and cingulate-precuneus&#xD;
      'task-negative' network. Our central hypotheses are that clinical improvement is associated&#xD;
      with: (i) normalization of reduced connectivity of regions within the 'task-positive'&#xD;
      network, with resultant increased inhibition of motor cortex, and (ii) normalization of low&#xD;
      task-related connectivity in regions within the task-negative network for MPH and the&#xD;
      'task-positive' network for ATX.&#xD;
&#xD;
      This research proposes to test a model which posits a neurophysiological basis of mechanisms&#xD;
      of response to stimulant and non-stimulant medications, and fits with our long term&#xD;
      objectives of being able to match treatments to individual patients. Testing this model&#xD;
      requires large samples of youth scanned using fMRI before and after treatment, and matched&#xD;
      healthy controls also scanned twice. We will use an innovative network-based approach to&#xD;
      study the effects of treatment, building on results from our current fMRI treatment study,&#xD;
      and incorporating new theoretical approaches to understanding ADHD and its treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">April 30, 2018</completion_date>
  <primary_completion_date type="Actual">April 30, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Correct Inhibition in Participants Assessed With the Go-No go Task</measure>
    <time_frame>Baseline and at 6 weeks</time_frame>
    <description>Comparison of Go-Nogo at 6 weeks from baseline. Performance on a go-nogo task inside the scanner (fMRI). In the go/no-go task, participants respond to certain stimuli (&quot;go&quot; stimuli) and make no response for others (&quot;no-go&quot; stimuli).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adult Attention Deficit Hyperactivity Disorder Investigator Symptom Rating Scale (ADHD-RS)</measure>
    <time_frame>8 weeks</time_frame>
    <description>ADHD-RS is an 18-item list of core ADHD symptoms, each item are scored on a 4-point scale from 0-3, with total 0-54, with higher score indicating more symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impressions-Severity (CGI-S)</measure>
    <time_frame>up to 6 weeks</time_frame>
    <description>a clinician rated measure of symptom severity. CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response Time in Attention Networks Test (ANT)</measure>
    <time_frame>baseline and at 6 weeks</time_frame>
    <description>A neuropsychological assessment of attention compared at 6 weeks from baseline by looking at response time. The ANT is a task designed to test three attentional networks in children and adults: alerting, orienting, and executive control. The response time were summed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Continuous Performance Test (CPT)</measure>
    <time_frame>baseline and at 6 weeks</time_frame>
    <description>A neuropsychological assessment of attention compared at 6 weeks from baseline. CPT is a task-oriented computerized assessment of attention-related problems.This score indicates the number of times the client responded but no target was presented. A fast reaction time and high commission error rate points to difficulties with impulsivity. A slow reaction time with high commission and omission errors, indicates inattention in general. Scores are compared with the normative scores for the age, group and gender of the person being tested and represented as a commissioned T-score. The T-score indicates the degree to which performance in CPT task is higher or lower than the performance of a healthy individual matched in age. A T-score of 50 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of more attention-related problems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Digit Span</measure>
    <time_frame>baseline and at 6 weeks</time_frame>
    <description>A cognitive/neuropsychological measure of auditory/verbal working memory compared at 6 weeks from baseline. Digit Span. Memory span is the longest list of items that a person can repeat back in correct order immediately after presentation on 50% of all trials. Items may include words, numbers, or letters. The task is known as digit span when numbers are used. Memory span is a common measure of short-term memory. A digit-span task is used to measure working memory's number storage capacity.The item score is the sum of the scores on the two trials for that item (range=0-2). The total raw score for backwards digit span is the sum of the item scores; maximum backwards digit span total raw score is 0-16 points. Higher score indicates better health outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Finger Windows</measure>
    <time_frame>baseline and at 6 weeks</time_frame>
    <description>A neuropsychological measure of motor skill and visual-spatial working memory compared at 6 weeks from baseline. The Finger Windows subtest is a measure of nonverbal, rote sequential recall. scaled scores ranging from 1 to 19, with higher score indicating better attention or concentration.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">127</enrollment>
  <condition>Attention Deficit Hyperactivity Disorder</condition>
  <condition>ADHD</condition>
  <arm_group>
    <arm_group_label>fMRI scans</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Atomoxetine arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Methylphenidate arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>fMRI scans</intervention_name>
    <description>2 fMRI scans 6-8 weeks apart</description>
    <arm_group_label>Atomoxetine arm</arm_group_label>
    <arm_group_label>Methylphenidate arm</arm_group_label>
    <arm_group_label>fMRI scans</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atomoxetine arm</intervention_name>
    <description>Flexible dose titration with atomoxetine prescribed at weekly visits for 6-8 weeks</description>
    <arm_group_label>Atomoxetine arm</arm_group_label>
    <other_name>Strattera</other_name>
    <other_name>ATX</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylphenidate arm</intervention_name>
    <description>Flexible dose titration with methylphenidate for 6-8 weeks, with optional post study stabilization visits.</description>
    <arm_group_label>Methylphenidate arm</arm_group_label>
    <other_name>Concerta</other_name>
    <other_name>MPH</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        General inclusion criteria for subjects with ADHD and healthy controls are:&#xD;
&#xD;
          -  aged 7-17 years;&#xD;
&#xD;
          -  Wechsler Intelligence Scale for Children (WISC) scores ≥ 75;&#xD;
&#xD;
          -  informed consent and assent to study participation.&#xD;
&#xD;
        Specific inclusion criteria for youth with ADHD are:&#xD;
&#xD;
          -  diagnosis of ADHD, any subtype, determined by Kiddie Schedule for Affective Disorders&#xD;
             and Schizophrenia for School-Aged Children-Present and Lifetime Versions (K-SADS-PL);&#xD;
&#xD;
          -  ADHD Rating Scale-IV-Parent Version: Investigator Administered (ADHD-RSIV) total score&#xD;
             ≥ 1.5 SD above age and gender means for subtype&#xD;
&#xD;
          -  Clinical Global Impressions-ADHD-Severity (CGI-S) score &gt; 4;&#xD;
&#xD;
          -  ADHD must be the primary diagnosis and focus of treatment, and the treatments offered&#xD;
             in the study must not be contraindicated for the comorbid disorder.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        General exclusion criteria are:&#xD;
&#xD;
          -  history of head injury with loss of consciousness or any CNS disease that is likely to&#xD;
             affect brain function;&#xD;
&#xD;
          -  diagnosis of autism or pervasive developmental, psychotic, major mood, and Tourette's&#xD;
             disorder;&#xD;
&#xD;
          -  alcohol or drug abuse in the past 3 months or a positive urinary toxic screen on&#xD;
             initial evaluation;&#xD;
&#xD;
          -  use of psychotropic medication within 2 weeks of the study (8 weeks for fluoxetine);&#xD;
&#xD;
          -  pre-existing medical or psychological condition which precludes being in the scanner&#xD;
             (e.g., claustrophobia, morbid obesity);&#xD;
&#xD;
          -  metal in the body that precludes scanning (e.g., braces, metal plate);&#xD;
&#xD;
          -  positive urine pregnancy test.&#xD;
&#xD;
        Specific exclusion criteria for the treatment trial include:&#xD;
&#xD;
          -  previous unsuccessful trial of MPH or ATX that was adequately dosed (≥ 1 mg/kg for MPH&#xD;
             or 1.0 mg/kg for ATX) and of adequate duration (≥ 4 weeks);&#xD;
&#xD;
          -  abnormal findings on physical exam, or vital signs&#xD;
&#xD;
          -  pulse and blood pressure &gt; 95% of age and gender mean;&#xD;
&#xD;
          -  inability to swallow capsules;&#xD;
&#xD;
          -  weight is &lt; 20 kg or &gt; 85 kg.&#xD;
&#xD;
        Specific exclusion criteria for control youth include:&#xD;
&#xD;
          -  no past history or current diagnosis of any psychiatric disorder, determined by the&#xD;
             K-SADS-PL interview;&#xD;
&#xD;
          -  ADHD-RS-IV and CBCL scores for each symptom domain ≤ 1 SD of age and gender means.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeffrey Newcorn, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kurt Schulz, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>August 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2012</study_first_posted>
  <results_first_submitted>May 22, 2019</results_first_submitted>
  <results_first_submitted_qc>July 7, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 24, 2020</results_first_posted>
  <last_update_submitted>July 7, 2020</last_update_submitted>
  <last_update_submitted_qc>July 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Icahn School of Medicine at Mount Sinai</investigator_affiliation>
    <investigator_full_name>Jeffrey Newcorn</investigator_full_name>
    <investigator_title>Director Division of Child and Adolescent Psychiatry, Associate Professor Psychiatry and Pediatrics, Medical Director Center for Excellence for ADHD and Related Disorders</investigator_title>
  </responsible_party>
  <keyword>Attention Deficit Hyperactivity Disorder</keyword>
  <keyword>Stimulant</keyword>
  <keyword>Non-stimulant</keyword>
  <keyword>Drug</keyword>
  <keyword>Methylphenidate</keyword>
  <keyword>Atomoxetine</keyword>
  <keyword>Strattera</keyword>
  <keyword>Concerta</keyword>
  <keyword>MACRO</keyword>
  <keyword>Medication</keyword>
  <keyword>Treatment</keyword>
  <keyword>Youth</keyword>
  <keyword>Adolescent</keyword>
  <keyword>Functional Magnetic Resonance Imaging</keyword>
  <keyword>Brain scan</keyword>
  <keyword>Imaging</keyword>
  <keyword>Response inhibition</keyword>
  <keyword>Inattentive</keyword>
  <keyword>Hyperactive</keyword>
  <keyword>Combined</keyword>
  <keyword>Medication Treatment</keyword>
  <keyword>Brain Imaging</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylphenidate</mesh_term>
    <mesh_term>Atomoxetine Hydrochloride</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 6, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/09/NCT01678209/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 22, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/09/NCT01678209/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment: 8/10/2012 - 4/30/17; Roll Over Year: 5/1/17 - 4/30/18; Youth with ADHD and Healthy Controls recruited from the community and clinics at Mount Sinai.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Control Group fMRI Scans Only</title>
          <description>Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart</description>
        </group>
        <group group_id="P2">
          <title>Atomoxetine Arm</title>
          <description>These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.</description>
        </group>
        <group group_id="P3">
          <title>Methylphenidate Arm</title>
          <description>Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
                <participants group_id="P2" count="40"/>
                <participants group_id="P3" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="22"/>
                <participants group_id="P3" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="18"/>
                <participants group_id="P3" count="18"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>could not scan twice</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>scheduling conflicts</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>screen fail</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="17"/>
                <participants group_id="P3" count="16"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Only participants with usable data were included in the data results</population>
      <group_list>
        <group group_id="B1">
          <title>Control Group fMRI Scans Only</title>
          <description>Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart</description>
        </group>
        <group group_id="B2">
          <title>Atomoxetine Arm</title>
          <description>These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.</description>
        </group>
        <group group_id="B3">
          <title>Methylphenidate Arm</title>
          <description>Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="47"/>
            <count group_id="B2" value="22"/>
            <count group_id="B3" value="22"/>
            <count group_id="B4" value="91"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13" spread="2.8"/>
                    <measurement group_id="B2" value="10" spread="3.02"/>
                    <measurement group_id="B3" value="12" spread="2.86"/>
                    <measurement group_id="B4" value="11" spread="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="51"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Correct Inhibition in Participants Assessed With the Go-No go Task</title>
        <description>Comparison of Go-Nogo at 6 weeks from baseline. Performance on a go-nogo task inside the scanner (fMRI). In the go/no-go task, participants respond to certain stimuli (&quot;go&quot; stimuli) and make no response for others (&quot;no-go&quot; stimuli).</description>
        <time_frame>Baseline and at 6 weeks</time_frame>
        <population>All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit. Thirty-one (N=31) controls were scanned twice for this project, but the second scan data for 1 subject was excluded from the analysis for motion. Thus, 31 control subjects were included in the analyses of</population>
        <group_list>
          <group group_id="O1">
            <title>Control Group fMRI Scans Only</title>
            <description>Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart</description>
          </group>
          <group group_id="O2">
            <title>Atomoxetine Arm</title>
            <description>These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.</description>
          </group>
          <group group_id="O3">
            <title>Methylphenidate Arm</title>
            <description>Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Correct Inhibition in Participants Assessed With the Go-No go Task</title>
          <description>Comparison of Go-Nogo at 6 weeks from baseline. Performance on a go-nogo task inside the scanner (fMRI). In the go/no-go task, participants respond to certain stimuli (&quot;go&quot; stimuli) and make no response for others (&quot;no-go&quot; stimuli).</description>
          <population>All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit. Thirty-one (N=31) controls were scanned twice for this project, but the second scan data for 1 subject was excluded from the analysis for motion. Thus, 31 control subjects were included in the analyses of</population>
          <units>percent correct inhibition</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="40"/>
                <count group_id="O3" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="47"/>
                    <count group_id="O2" value="40"/>
                    <count group_id="O3" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79.08" spread="15.07"/>
                    <measurement group_id="O2" value="79.43" spread="17.27"/>
                    <measurement group_id="O3" value="77.98" spread="15.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="31"/>
                    <count group_id="O2" value="22"/>
                    <count group_id="O3" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78.24" spread="16.57"/>
                    <measurement group_id="O2" value="80.72" spread="14.22"/>
                    <measurement group_id="O3" value="81.81" spread="14.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adult Attention Deficit Hyperactivity Disorder Investigator Symptom Rating Scale (ADHD-RS)</title>
        <description>ADHD-RS is an 18-item list of core ADHD symptoms, each item are scored on a 4-point scale from 0-3, with total 0-54, with higher score indicating more symptoms.</description>
        <time_frame>8 weeks</time_frame>
        <population>All participants in control group including the one subject who could not be scanned twice included in data analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Control Group fMRI Scans Only</title>
            <description>Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart</description>
          </group>
          <group group_id="O2">
            <title>Atomoxetine Arm</title>
            <description>These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.</description>
          </group>
          <group group_id="O3">
            <title>Methylphenidate Arm</title>
            <description>Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Adult Attention Deficit Hyperactivity Disorder Investigator Symptom Rating Scale (ADHD-RS)</title>
          <description>ADHD-RS is an 18-item list of core ADHD symptoms, each item are scored on a 4-point scale from 0-3, with total 0-54, with higher score indicating more symptoms.</description>
          <population>All participants in control group including the one subject who could not be scanned twice included in data analysis.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="22"/>
                <count group_id="O3" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" spread="2"/>
                    <measurement group_id="O2" value="15" spread="11"/>
                    <measurement group_id="O3" value="18" spread="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Global Impressions-Severity (CGI-S)</title>
        <description>a clinician rated measure of symptom severity. CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.</description>
        <time_frame>up to 6 weeks</time_frame>
        <population>All participants in control group including the one subject who could not be scanned twice included in data analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Control Group fMRI Scans Only</title>
            <description>Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart</description>
          </group>
          <group group_id="O2">
            <title>Atomoxetine Arm</title>
            <description>These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.</description>
          </group>
          <group group_id="O3">
            <title>Methylphenidate Arm</title>
            <description>Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Global Impressions-Severity (CGI-S)</title>
          <description>a clinician rated measure of symptom severity. CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.</description>
          <population>All participants in control group including the one subject who could not be scanned twice included in data analysis.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="22"/>
                <count group_id="O3" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" spread="0"/>
                    <measurement group_id="O2" value="3.2" spread="1.6"/>
                    <measurement group_id="O3" value="3.4" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Response Time in Attention Networks Test (ANT)</title>
        <description>A neuropsychological assessment of attention compared at 6 weeks from baseline by looking at response time. The ANT is a task designed to test three attentional networks in children and adults: alerting, orienting, and executive control. The response time were summed.</description>
        <time_frame>baseline and at 6 weeks</time_frame>
        <population>All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Control Group fMRI Scans Only</title>
            <description>Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart</description>
          </group>
          <group group_id="O2">
            <title>Atomoxetine Arm</title>
            <description>These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.</description>
          </group>
          <group group_id="O3">
            <title>Methylphenidate Arm</title>
            <description>Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Response Time in Attention Networks Test (ANT)</title>
          <description>A neuropsychological assessment of attention compared at 6 weeks from baseline by looking at response time. The ANT is a task designed to test three attentional networks in children and adults: alerting, orienting, and executive control. The response time were summed.</description>
          <population>All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit.</population>
          <units>milliseconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="40"/>
                <count group_id="O3" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="47"/>
                    <count group_id="O2" value="40"/>
                    <count group_id="O3" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="817.50" spread="171.06"/>
                    <measurement group_id="O2" value="856.60" spread="179.34"/>
                    <measurement group_id="O3" value="885.68" spread="170.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="31"/>
                    <count group_id="O2" value="22"/>
                    <count group_id="O3" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="756.87" spread="153.83"/>
                    <measurement group_id="O2" value="826.14" spread="139.08"/>
                    <measurement group_id="O3" value="783.09" spread="125.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Continuous Performance Test (CPT)</title>
        <description>A neuropsychological assessment of attention compared at 6 weeks from baseline. CPT is a task-oriented computerized assessment of attention-related problems.This score indicates the number of times the client responded but no target was presented. A fast reaction time and high commission error rate points to difficulties with impulsivity. A slow reaction time with high commission and omission errors, indicates inattention in general. Scores are compared with the normative scores for the age, group and gender of the person being tested and represented as a commissioned T-score. The T-score indicates the degree to which performance in CPT task is higher or lower than the performance of a healthy individual matched in age. A T-score of 50 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of more attention-related problems.</description>
        <time_frame>baseline and at 6 weeks</time_frame>
        <population>All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Control Group fMRI Scans Only</title>
            <description>Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart</description>
          </group>
          <group group_id="O2">
            <title>Atomoxetine Arm</title>
            <description>These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.</description>
          </group>
          <group group_id="O3">
            <title>Methylphenidate Arm</title>
            <description>Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Continuous Performance Test (CPT)</title>
          <description>A neuropsychological assessment of attention compared at 6 weeks from baseline. CPT is a task-oriented computerized assessment of attention-related problems.This score indicates the number of times the client responded but no target was presented. A fast reaction time and high commission error rate points to difficulties with impulsivity. A slow reaction time with high commission and omission errors, indicates inattention in general. Scores are compared with the normative scores for the age, group and gender of the person being tested and represented as a commissioned T-score. The T-score indicates the degree to which performance in CPT task is higher or lower than the performance of a healthy individual matched in age. A T-score of 50 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of more attention-related problems.</description>
          <population>All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit.</population>
          <units>commissioned t-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="40"/>
                <count group_id="O3" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="47"/>
                    <count group_id="O2" value="40"/>
                    <count group_id="O3" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.65" spread="11.29"/>
                    <measurement group_id="O2" value="55.26" spread="5.62"/>
                    <measurement group_id="O3" value="52.94" spread="9.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="31"/>
                    <count group_id="O2" value="22"/>
                    <count group_id="O3" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.64" spread="9.70"/>
                    <measurement group_id="O2" value="50.70" spread="8.66"/>
                    <measurement group_id="O3" value="48.46" spread="10.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Digit Span</title>
        <description>A cognitive/neuropsychological measure of auditory/verbal working memory compared at 6 weeks from baseline. Digit Span. Memory span is the longest list of items that a person can repeat back in correct order immediately after presentation on 50% of all trials. Items may include words, numbers, or letters. The task is known as digit span when numbers are used. Memory span is a common measure of short-term memory. A digit-span task is used to measure working memory's number storage capacity.The item score is the sum of the scores on the two trials for that item (range=0-2). The total raw score for backwards digit span is the sum of the item scores; maximum backwards digit span total raw score is 0-16 points. Higher score indicates better health outcomes.</description>
        <time_frame>baseline and at 6 weeks</time_frame>
        <population>All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Control Group fMRI Scans Only</title>
            <description>Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart</description>
          </group>
          <group group_id="O2">
            <title>Atomoxetine Arm</title>
            <description>These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.</description>
          </group>
          <group group_id="O3">
            <title>Methylphenidate Arm</title>
            <description>Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Digit Span</title>
          <description>A cognitive/neuropsychological measure of auditory/verbal working memory compared at 6 weeks from baseline. Digit Span. Memory span is the longest list of items that a person can repeat back in correct order immediately after presentation on 50% of all trials. Items may include words, numbers, or letters. The task is known as digit span when numbers are used. Memory span is a common measure of short-term memory. A digit-span task is used to measure working memory's number storage capacity.The item score is the sum of the scores on the two trials for that item (range=0-2). The total raw score for backwards digit span is the sum of the item scores; maximum backwards digit span total raw score is 0-16 points. Higher score indicates better health outcomes.</description>
          <population>All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="40"/>
                <count group_id="O3" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="47"/>
                    <count group_id="O2" value="40"/>
                    <count group_id="O3" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.30" spread="18.76"/>
                    <measurement group_id="O2" value="9.25" spread="2.06"/>
                    <measurement group_id="O3" value="7.5" spread="1.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="31"/>
                    <count group_id="O2" value="22"/>
                    <count group_id="O3" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.39" spread="1.58"/>
                    <measurement group_id="O2" value="9.75" spread="0.95"/>
                    <measurement group_id="O3" value="8.5" spread="1.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Finger Windows</title>
        <description>A neuropsychological measure of motor skill and visual-spatial working memory compared at 6 weeks from baseline. The Finger Windows subtest is a measure of nonverbal, rote sequential recall. scaled scores ranging from 1 to 19, with higher score indicating better attention or concentration.</description>
        <time_frame>baseline and at 6 weeks</time_frame>
        <population>All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Control Group fMRI Scans Only</title>
            <description>Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart</description>
          </group>
          <group group_id="O2">
            <title>Atomoxetine Arm</title>
            <description>These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.</description>
          </group>
          <group group_id="O3">
            <title>Methylphenidate Arm</title>
            <description>Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Finger Windows</title>
          <description>A neuropsychological measure of motor skill and visual-spatial working memory compared at 6 weeks from baseline. The Finger Windows subtest is a measure of nonverbal, rote sequential recall. scaled scores ranging from 1 to 19, with higher score indicating better attention or concentration.</description>
          <population>All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="40"/>
                <count group_id="O3" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="47"/>
                    <count group_id="O2" value="40"/>
                    <count group_id="O3" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.04" spread="3.69"/>
                    <measurement group_id="O2" value="14.50" spread="2.64"/>
                    <measurement group_id="O3" value="16.50" spread="5.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="31"/>
                    <count group_id="O2" value="22"/>
                    <count group_id="O3" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.65" spread="5.33"/>
                    <measurement group_id="O2" value="16.25" spread="6.65"/>
                    <measurement group_id="O3" value="16.25" spread="6.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>8 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>fMRI Scans</title>
          <description>Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart</description>
        </group>
        <group group_id="E2">
          <title>Atomoxetine Arm</title>
          <description>These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.</description>
        </group>
        <group group_id="E3">
          <title>Methylphenidate Arm</title>
          <description>Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Stomachache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Common cold/allergies</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Sleep problems</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Lightheaded/dizzy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Moody/irritable</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Anxious</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Increased blood pressure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Dr. Newcorn has FCOI reporting obligations as stipulated by the Mount Sinai FCOI committee</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Beth Krone, PhD</name_or_title>
      <organization>Icahn School of Medicine at Mount Sinai</organization>
      <phone>212-241-8014</phone>
      <email>beth.krone@mssm.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01678209
org study id: GCO 11-0161
secondary id: 5R01MH095766-02
nct id: NCT01678209
lead sponsor: 
collaborator: 
has dmc: Yes
The growing number of medications used to treat attention-deficit/hyperactivity disorder
      (ADHD) raises important questions about whether different medications have similar or
      different therapeutic mechanisms of action. We have recently shown that the stimulant
      methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) produce clinical improvement
      via a common mechanism in motor cortex, and distinct actions in frontostriatal and midline
      cingulate-precuneus regions. These exciting findings offer a window into the common and
      unique neurophysiological mechanisms of response to stimulant and non-stimulant treatments.
      However, the interpretation and clinical utility of these results would be greatly enhanced
      by in-depth investigation of the impact of the two treatments on relevant neural networks,
      and analyses which evaluate whether improvement is achieved via normalization or other
      adaptive changes in brain function.
The specific aims of this project are to use functional magnetic resonance imaging (fMRI) to
      determine the significance of activation changes over treatment related to clinical
      improvement, and the impact of treatment on neural connectivity within and between the
      anti-correlated frontostriatal 'task-positive' circuit and cingulate-precuneus
      'task-negative' network. Our central hypotheses are that clinical improvement is associated
      with: (i) normalization of reduced connectivity of regions within the 'task-positive'
      network, with resultant increased inhibition of motor cortex, and (ii) normalization of low
      task-related connectivity in regions within the task-negative network for MPH and the
      'task-positive' network for ATX.

      This research proposes to test a model which posits a neurophysiological basis of mechanisms
      of response to stimulant and non-stimulant medications, and fits with our long term
      objectives of being able to match treatments to individual patients. Testing this model
      requires large samples of youth scanned using fMRI before and after treatment, and matched
      healthy controls also scanned twice. We will use an innovative network-based approach to
      study the effects of treatment, building on results from our current fMRI treatment study,
      and incorporating new theoretical approaches to understanding ADHD and its treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Correct Inhibition in Participants Assessed With the Go-No go Task
time frame: Baseline and at 6 weeks
description: Comparison of Go-Nogo at 6 weeks from baseline. Performance on a go-nogo task inside the scanner (fMRI). In the go/no-go task, participants respond to certain stimuli ("go" stimuli) and make no response for others ("no-go" stimuli).
measure: Adult Attention Deficit Hyperactivity Disorder Investigator Symptom Rating Scale (ADHD-RS)
time frame: 8 weeks
description: ADHD-RS is an 18-item list of core ADHD symptoms, each item are scored on a 4-point scale from 0-3, with total 0-54, with higher score indicating more symptoms.
measure: Clinical Global Impressions-Severity (CGI-S)
time frame: up to 6 weeks
description: a clinician rated measure of symptom severity. CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
measure: Response Time in Attention Networks Test (ANT)
time frame: baseline and at 6 weeks
description: A neuropsychological assessment of attention compared at 6 weeks from baseline by looking at response time. The ANT is a task designed to test three attentional networks in children and adults: alerting, orienting, and executive control. The response time were summed.
measure: Continuous Performance Test (CPT)
time frame: baseline and at 6 weeks
description: A neuropsychological assessment of attention compared at 6 weeks from baseline. CPT is a task-oriented computerized assessment of attention-related problems.This score indicates the number of times the client responded but no target was presented. A fast reaction time and high commission error rate points to difficulties with impulsivity. A slow reaction time with high commission and omission errors, indicates inattention in general. Scores are compared with the normative scores for the age, group and gender of the person being tested and represented as a commissioned T-score. The T-score indicates the degree to which performance in CPT task is higher or lower than the performance of a healthy individual matched in age. A T-score of 50 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of more attention-related problems.
measure: Digit Span
time frame: baseline and at 6 weeks
description: A cognitive/neuropsychological measure of auditory/verbal working memory compared at 6 weeks from baseline. Digit Span. Memory span is the longest list of items that a person can repeat back in correct order immediately after presentation on 50% of all trials. Items may include words, numbers, or letters. The task is known as digit span when numbers are used. Memory span is a common measure of short-term memory. A digit-span task is used to measure working memory's number storage capacity.The item score is the sum of the scores on the two trials for that item (range=0-2). The total raw score for backwards digit span is the sum of the item scores; maximum backwards digit span total raw score is 0-16 points. Higher score indicates better health outcomes.
measure: Finger Windows
time frame: baseline and at 6 weeks
description: A neuropsychological measure of motor skill and visual-spatial working memory compared at 6 weeks from baseline. The Finger Windows subtest is a measure of nonverbal, rote sequential recall. scaled scores ranging from 1 to 19, with higher score indicating better attention or concentration.
arm group label: fMRI scans
arm group type: Active Comparator
description: Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart
arm group label: Atomoxetine arm
arm group type: Experimental
description: These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.
arm group label: Methylphenidate arm
arm group type: Experimental
description: Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.
intervention type: Other
intervention name: fMRI scans
description: 2 fMRI scans 6-8 weeks apart
arm group label: Atomoxetine arm
arm group label: Methylphenidate arm
arm group label: fMRI scans
intervention type: Drug
intervention name: Atomoxetine arm
description: Flexible dose titration with atomoxetine prescribed at weekly visits for 6-8 weeks
arm group label: Atomoxetine arm
other name: Strattera
other name: ATX
intervention type: Drug
intervention name: Methylphenidate arm
description: Flexible dose titration with methylphenidate for 6-8 weeks, with optional post study stabilization visits.
arm group label: Methylphenidate arm
other name: Concerta
other name: MPH
criteria: 
gender: All
minimum age: 7 Years
maximum age: 17 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jeffrey Newcorn, MD
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
last name: Kurt Schulz, PhD
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Icahn School of Medicine at Mount Sinai
investigator full name: Jeffrey Newcorn
investigator title: Director Division of Child and Adolescent Psychiatry, Associate Professor Psychiatry and Pediatrics, Medical Director Center for Excellence for ADHD and Related Disorders
mesh term: Hyperkinesis
mesh term: Attention Deficit Disorder with Hyperactivity
mesh term: Methylphenidate
mesh term: Atomoxetine Hydrochloride
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 