<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/NCT02259517</url>
  </required_header>
  <id_info>
    <org_study_id>6961</org_study_id>
    <nct_id>NCT02259517</nct_id>
  </id_info>
  <brief_title>An fMRI Study of Stimulant vs. Non-Stimulant Treatment of ADHD</brief_title>
  <official_title>Imaging Stimulant vs. Non-Stimulant Treatment of Attention Deficit Hyperactivity Disorder (ADHD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New York State Psychiatric Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>American Academy of Child Adolescent Psychiatry.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shire</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>New York State Psychiatric Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Children with Attention-Deficit/Hyperactivity Disorder (ADHD) are typically treated with two&#xD;
      types of medications with differing mechanisms of action: stimulants and non-stimulants. The&#xD;
      stimulant Vyvanse (lisdexamfetamine, LDX), and the non-stimulant Intuniv (extended-release&#xD;
      guanfacine, GXR), are both FDA approved treatment for ADHD. Clinical trials have shown that&#xD;
      both medications are effective in reducing ADHD symptoms, although the neurobiological&#xD;
      mechanisms by which Vyvanse and Intuniv produce these effects remain unknown. The aim of this&#xD;
      study is to examine the mechanisms by which LDX and GXR reduce symptoms in patients with&#xD;
      ADHD. MRI scanning will be used to identify treatment-related changes in brain structure and&#xD;
      function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Children with ADHD and age and sex-matched healthy controls will be scanned at the beginning&#xD;
      of the study. In this first part of the study, MRI findings will be compared between the two&#xD;
      groups to see whether brain functioning of children with ADHD differs from that of healthy&#xD;
      children. In the second part of the study, the children with ADHD will meet weekly with the&#xD;
      study doctor and be administered either extended-release guanfacine (Intuniv) or&#xD;
      lisdexamfetamine (Vyvanse) for 6 weeks. Selection into either treatment group will be&#xD;
      randomly determined. At the end of the study, the children with ADHD treated with either&#xD;
      medication will have a second MRI scan. The findings of that second MRI scan will be compared&#xD;
      to the first MRI scan in order to examine brain changes due to the medication. These second&#xD;
      MRI scans will also be compared to the scans of the healthy controls.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Recruitment/enrollment ended early due to the COVID-19 pandemic&#xD;
  </why_stopped>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">November 6, 2021</completion_date>
  <primary_completion_date type="Actual">November 6, 2021</primary_completion_date>
  <phase>N/A</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in Brain Segmentation Volume Produced by Stimulant or Non-stimulant Medications in Patients With ADHD</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Brain segmentation volume measured in mm^3. We are reporting the mean difference in brain segmentation volume from baseline (pre-test) to 6 weeks (post-test).&#xD;
No statistical analysis information is being submitted for the affected outcome measure. No statistical analyses have been performed or would be considered scientifically appropriate because actual enrollment fell well below target enrollment. Enrollment terminated early as a result of the COVID-19 pandemic.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Attention Deficit Hyperactivity Disorder</condition>
  <arm_group>
    <arm_group_label>Guanfacine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be administered extended-release guanfacine, which is in tablet form, and will be instructed to take the medication once daily for 6 weeks. The daily dose will range between 1 and 4 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lisdexamfetamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be administered lisdexamfetamine, which is in tablet form, and will be instructed to take the medication daily for 6 weeks. The daily dose will range between 30 and 70mg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Guanfacine</intervention_name>
    <description>Participants will meet with the study doctor on a weekly basis during the treatment phase of the study. In the first few weeks, the daily dose of the medication will be individually adjusted by the study doctor according to participants' clinical response to and tolerability of the medication. The optimal dose will then be maintained for the remainder of the treatment period.</description>
    <arm_group_label>Guanfacine</arm_group_label>
    <other_name>Intuniv</other_name>
    <other_name>GXR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lisdexamfetamine</intervention_name>
    <description>Participants will meet with the study doctor on a weekly basis during the treatment phase of the study. In the first few weeks, the daily dose of the medication will be individually adjusted by the study doctor according to participants' clinical response to and tolerability of the medication. The optimal dose will then be maintained for the remainder of the treatment period.</description>
    <arm_group_label>Lisdexamfetamine</arm_group_label>
    <other_name>Vyvanse</other_name>
    <other_name>LDX</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        ADHD Participants:&#xD;
&#xD;
          -  The participant satisfies Diagnostic and Statistical Manual of Mental Disorders&#xD;
             (DSM-5) criteria for a primary diagnosis of ADHD, any subtype.&#xD;
&#xD;
        Healthy Control Participants:&#xD;
&#xD;
          -  The participant must have no current DSM Axis I psychiatric disorder.&#xD;
&#xD;
        All Participants:&#xD;
&#xD;
          -  Participants must provide assent and a legal guardian must provide consent.&#xD;
&#xD;
          -  The participant is male or female and between 6 - 17 years of age and in good physical&#xD;
             health.&#xD;
&#xD;
          -  Girls of childbearing potential must have a negative urine pregnancy test and, if&#xD;
             sexually active, must be using adequate contraception.&#xD;
&#xD;
          -  The participant is English speaking.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        ADHD Participants:&#xD;
&#xD;
          -  The participant has a current comorbid DSM Axis I psychiatric diagnosis or other&#xD;
             symptomatic manifestations that, in the opinion of the study doctor, will&#xD;
             contraindicate lisdexamfetamine or guanfacine treatment or confound safety&#xD;
             assessments.&#xD;
&#xD;
          -  The participant meets DSM-5 criteria for current substance abuse and/or dependence.&#xD;
&#xD;
          -  The participant is currently taking or has taken within the past 4 months, a&#xD;
             psychotropic medication.&#xD;
&#xD;
          -  The participant has a documented allergy or intolerance to lisdexamfetamine or&#xD;
             guanfacine products.&#xD;
&#xD;
          -  The participant has a diagnosis or a history of cardiovascular disease or any other&#xD;
             serious medical illness.&#xD;
&#xD;
          -  The participant is pregnant or lactating.&#xD;
&#xD;
          -  The participant is actively suicidal.&#xD;
&#xD;
          -  MRI contraindications (e.g., irremovable metal on the body, pacemaker, braces)&#xD;
&#xD;
          -  The participant has a full-scale intelligence quotient (IQ) less than 70.&#xD;
&#xD;
          -  The participant has a history of seizure (except febrile seizure).&#xD;
&#xD;
        Healthy Controls:&#xD;
&#xD;
          -  The participant meets DSM criteria for current substance abuse and/or dependence.&#xD;
&#xD;
          -  The participant is currently taking a psychotropic medication.&#xD;
&#xD;
          -  The participant has a history of a serious medical illness.&#xD;
&#xD;
          -  The participant is pregnant or lactating.&#xD;
&#xD;
          -  MRI contraindications (e.g., irremovable metal on the body, pacemaker, braces)&#xD;
&#xD;
          -  The participant has a full-scale intelligence quotient (IQ) less than 70.&#xD;
&#xD;
          -  The participant has a history of seizure (except febrile seizure).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jonathan Posner, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>New York State Psychiatric Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>New York State Psychiatric Institute</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>September 30, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2014</study_first_posted>
  <results_first_submitted>October 5, 2022</results_first_submitted>
  <results_first_submitted_qc>January 18, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">February 2, 2023</results_first_posted>
  <last_update_submitted>January 18, 2023</last_update_submitted>
  <last_update_submitted_qc>January 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>New York State Psychiatric Institute</investigator_affiliation>
    <investigator_full_name>Jonathan Posner</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>ADHD</keyword>
  <keyword>Intuniv</keyword>
  <keyword>Non-stimulant</keyword>
  <keyword>Guanfacine extended-release</keyword>
  <keyword>Vyvanse</keyword>
  <keyword>Stimulant</keyword>
  <keyword>Lisdexamfetamine</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>Guanfacine</mesh_term>
    <mesh_term>Lisdexamfetamine Dimesylate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>July 10, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT02259517/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>July 10, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT02259517/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment started in 2014 and ended in 2020. Participants were primarily recruited from the community through advertisements in local newspapers and flyers posted in local establishments. Participants were also recruited from other research studies and doctor's offices.</recruitment_details>
      <pre_assignment_details>5 ADHD participants withdrew or were excluded from the study prior to randomization and thus are not included. Participants who withdrew were no longer interested in treatment or were lost to follow-up. Participants were excluded due to subthreshold ADHD symptoms, comorbid psychiatric conditions, &amp; MRI contraindications.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>ADHD - Guanfacine</title>
          <description>ADHD participants who were randomized to receive guanfacine for 6 weeks of treatment</description>
        </group>
        <group group_id="P2">
          <title>ADHD - Lisdexamfetamine</title>
          <description>ADHD participants who were randomized to receive lisdexamfetamine for 6 weeks of treatment</description>
        </group>
        <group group_id="P3">
          <title>Healthy Controls</title>
          <description>Age- and sex- matched healthy control participants; baseline procedures only</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Psychiatric diagnosis (e.g., ADHD, MDD)</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Baseline analysis population includes participants who completed the study.</population>
      <group_list>
        <group group_id="B1">
          <title>ADHD - Guanfacine</title>
          <description>ADHD participants who were randomized to receive guanfacine for 6 weeks of treatment</description>
        </group>
        <group group_id="B2">
          <title>ADHD - Lisdexamfetamine</title>
          <description>ADHD participants who were randomized to receive lisdexamfetamine for 6 weeks of treatment</description>
        </group>
        <group group_id="B3">
          <title>Healthy Controls</title>
          <description>Age- and sex- matched healthy control participants; baseline procedures only</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="5"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="15"/>
            <count group_id="B4" value="24"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="5"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10" spread="2.35"/>
                    <measurement group_id="B2" value="8.75" spread="0.96"/>
                    <measurement group_id="B3" value="9.6" spread="2.47"/>
                    <measurement group_id="B4" value="9.54" spread="2.23"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="5"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="14"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="5"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</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>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="13"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="5"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Behavior Rating Inventory of Executive Function, 2nd Edition - Global Executive Composite</title>
          <description>The Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) assesses executive function in children and adolescents ages 5-18 years old. The Global Executive Composite (GEC) is an overall summary score and reflects all the clinical scales of the BRIEF-2. Higher scores indicate lower levels of executive functioning. Parent-report T-scores on the GEC are reported below (population mean = 50, population standard deviation = 10).</description>
          <population>One Healthy Control participant was missing the parent-report BRIEF-2.</population>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="5"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="14"/>
                    <count group_id="B4" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65.33" spread="7.77"/>
                    <measurement group_id="B2" value="62.5" spread="9.33"/>
                    <measurement group_id="B3" value="44.57" spread="12.38"/>
                    <measurement group_id="B4" value="52.22" spread="14.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Changes in Brain Segmentation Volume Produced by Stimulant or Non-stimulant Medications in Patients With ADHD</title>
        <description>Brain segmentation volume measured in mm^3. We are reporting the mean difference in brain segmentation volume from baseline (pre-test) to 6 weeks (post-test).&#xD;
No statistical analysis information is being submitted for the affected outcome measure. No statistical analyses have been performed or would be considered scientifically appropriate because actual enrollment fell well below target enrollment. Enrollment terminated early as a result of the COVID-19 pandemic.</description>
        <time_frame>Baseline and 6 weeks</time_frame>
        <population>4 subjects from the ADHD-Guanfacine group and 3 subjects from the ADHD-Lisdexamfetamine group had usable anatomical MRI data at baseline and follow-up. HCs did not complete follow-up.&#xD;
No statistical analysis information is being submitted for the affected outcome measure. No statistical analyses have been performed or would be considered scientifically appropriate because actual enrollment fell well below target enrollment. Enrollment terminated early as a result of the COVID-19 pandemic.</population>
        <group_list>
          <group group_id="O1">
            <title>ADHD - Guanfacine</title>
            <description>ADHD participants who were randomized to receive guanfacine for 6 weeks of treatment</description>
          </group>
          <group group_id="O2">
            <title>ADHD - Lisdexamfetamine</title>
            <description>ADHD participants who were randomized to receive lisdexamfetamine for 6 weeks of treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Brain Segmentation Volume Produced by Stimulant or Non-stimulant Medications in Patients With ADHD</title>
          <description>Brain segmentation volume measured in mm^3. We are reporting the mean difference in brain segmentation volume from baseline (pre-test) to 6 weeks (post-test).&#xD;
No statistical analysis information is being submitted for the affected outcome measure. No statistical analyses have been performed or would be considered scientifically appropriate because actual enrollment fell well below target enrollment. Enrollment terminated early as a result of the COVID-19 pandemic.</description>
          <population>4 subjects from the ADHD-Guanfacine group and 3 subjects from the ADHD-Lisdexamfetamine group had usable anatomical MRI data at baseline and follow-up. HCs did not complete follow-up.&#xD;
No statistical analysis information is being submitted for the affected outcome measure. No statistical analyses have been performed or would be considered scientifically appropriate because actual enrollment fell well below target enrollment. Enrollment terminated early as a result of the COVID-19 pandemic.</population>
          <units>mm^3</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6137" spread="14393"/>
                    <measurement group_id="O2" value="11833" spread="39942"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected through study completion, an average of 6 weeks.</time_frame>
      <desc>Adverse events were routinely collected from ADHD participants receiving treatment using the Pittsburgh Side Effects Rating Scale. A physician met with participants in person approximately once per week during treatment. The physician was also available by phone between visits.&#xD;
HC participants completed a baseline assessment and did not receive any intervention; therefore, there was no monitoring for adverse events.</desc>
      <group_list>
        <group group_id="E1">
          <title>Guanfacine</title>
          <description>Participants will be administered extended-release guanfacine, which is in tablet form, and will be instructed to take the medication once daily for 6 weeks. The daily dose will range between 1 and 4 mg.&#xD;
Guanfacine: Participants will meet with the study doctor on a weekly basis during the treatment phase of the study. In the first few weeks, the daily dose of the medication will be individually adjusted by the study doctor according to participants' clinical response to and tolerability of the medication. The optimal dose will then be maintained for the remainder of the treatment period.</description>
        </group>
        <group group_id="E2">
          <title>Lisdexamfetamine</title>
          <description>Participants will be administered lisdexamfetamine, which is in tablet form, and will be instructed to take the medication daily for 6 weeks. The daily dose will range between 30 and 70mg.&#xD;
Lisdexamfetamine: Participants will meet with the study doctor on a weekly basis during the treatment phase of the study. In the first few weeks, the daily dose of the medication will be individually adjusted by the study doctor according to participants' clinical response to and tolerability of the medication. The optimal dose will then be maintained for the remainder of the treatment period.</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="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>No statistical analysis information is being submitted for the affected outcome measure. No statistical analyses have been performed or would be considered scientifically appropriate because actual enrollment fell well below target enrollment. Enrollment terminated early as a result of the COVID-19 pandemic.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Jonathan Posner, MD</name_or_title>
      <organization>Duke University</organization>
      <phone>1 919 684 2403</phone>
      <email>jonathan.posner@duke.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/NCT02259517
org study id: 6961
nct id: NCT02259517
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Children with Attention-Deficit/Hyperactivity Disorder (ADHD) are typically treated with two
      types of medications with differing mechanisms of action: stimulants and non-stimulants. The
      stimulant Vyvanse (lisdexamfetamine, LDX), and the non-stimulant Intuniv (extended-release
      guanfacine, GXR), are both FDA approved treatment for ADHD. Clinical trials have shown that
      both medications are effective in reducing ADHD symptoms, although the neurobiological
      mechanisms by which Vyvanse and Intuniv produce these effects remain unknown. The aim of this
      study is to examine the mechanisms by which LDX and GXR reduce symptoms in patients with
      ADHD. MRI scanning will be used to identify treatment-related changes in brain structure and
      function.
Children with ADHD and age and sex-matched healthy controls will be scanned at the beginning
      of the study. In this first part of the study, MRI findings will be compared between the two
      groups to see whether brain functioning of children with ADHD differs from that of healthy
      children. In the second part of the study, the children with ADHD will meet weekly with the
      study doctor and be administered either extended-release guanfacine (Intuniv) or
      lisdexamfetamine (Vyvanse) for 6 weeks. Selection into either treatment group will be
      randomly determined. At the end of the study, the children with ADHD treated with either
      medication will have a second MRI scan. The findings of that second MRI scan will be compared
      to the first MRI scan in order to examine brain changes due to the medication. These second
      MRI scans will also be compared to the scans of the healthy controls.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Changes in Brain Segmentation Volume Produced by Stimulant or Non-stimulant Medications in Patients With ADHD
time frame: Baseline and 6 weeks
description: Brain segmentation volume measured in mm^3. We are reporting the mean difference in brain segmentation volume from baseline (pre-test) to 6 weeks (post-test).
No statistical analysis information is being submitted for the affected outcome measure. No statistical analyses have been performed or would be considered scientifically appropriate because actual enrollment fell well below target enrollment. Enrollment terminated early as a result of the COVID-19 pandemic.
arm group label: Guanfacine
arm group type: Experimental
description: Participants will be administered extended-release guanfacine, which is in tablet form, and will be instructed to take the medication once daily for 6 weeks. The daily dose will range between 1 and 4 mg.
arm group label: Lisdexamfetamine
arm group type: Experimental
description: Participants will be administered lisdexamfetamine, which is in tablet form, and will be instructed to take the medication daily for 6 weeks. The daily dose will range between 30 and 70mg.
intervention type: Drug
intervention name: Guanfacine
description: Participants will meet with the study doctor on a weekly basis during the treatment phase of the study. In the first few weeks, the daily dose of the medication will be individually adjusted by the study doctor according to participants' clinical response to and tolerability of the medication. The optimal dose will then be maintained for the remainder of the treatment period.
arm group label: Guanfacine
other name: Intuniv
other name: GXR
intervention type: Drug
intervention name: Lisdexamfetamine
description: Participants will meet with the study doctor on a weekly basis during the treatment phase of the study. In the first few weeks, the daily dose of the medication will be individually adjusted by the study doctor according to participants' clinical response to and tolerability of the medication. The optimal dose will then be maintained for the remainder of the treatment period.
arm group label: Lisdexamfetamine
other name: Vyvanse
other name: LDX
criteria: 
gender: All
minimum age: 6 Years
maximum age: 17 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jonathan Posner, MD
role: Principal Investigator
affiliation: New York State Psychiatric Institute
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: New York State Psychiatric Institute
investigator full name: Jonathan Posner
investigator title: Associate Professor
mesh term: Hyperkinesis
mesh term: Attention Deficit Disorder with Hyperactivity
mesh term: Guanfacine
mesh term: Lisdexamfetamine Dimesylate
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: No statistical analysis information is being submitted for the affected outcome measure. No statistical analyses have been performed or would be considered scientifically appropriate because actual enrollment fell well below target enrollment. Enrollment terminated early as a result of the COVID-19 pandemic.
point of contact: 