<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/NCT01709695</url>
  </required_header>
  <id_info>
    <org_study_id>GCO 09-1825</org_study_id>
    <secondary_id>HSM:10-00415</secondary_id>
    <nct_id>NCT01709695</nct_id>
  </id_info>
  <brief_title>Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With ADHD</brief_title>
  <official_title>Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With Attention-deficit/Hyperactivity Disorder (ADHD): an Functional Magnetic Resonance Imaging(fMRI) Study of Brain Activation Pre and Post Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Icahn School of Medicine at Mount Sinai</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Icahn School of Medicine at Mount Sinai</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study proposes to evaluate the effects of guanfacine extended release on brain&#xD;
      activation during fMRI in children and adolescents with ADHD between the ages 8-15 and ADHD&#xD;
      subjects randomized to placebo treatment.&#xD;
&#xD;
      This study also proposes to collect DNA on study participants, to examine the genetic&#xD;
      underpinning of the observed fMRI activation profiles at baseline and in response to&#xD;
      treatment. The purpose is to examine polymorphisms of the adrenergic 2A gene (and other&#xD;
      related targets) for genetic biomarkers in association with the fMRI findings of this study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study proposes to evaluate the effects of guanfacine on brain activation during fMRI in&#xD;
      12 children and adolescents ages 8 - 15 with ADHD treated with once-daily INTUNIV(TM)&#xD;
      (guanfacine; GXR) extended release tablets and 12 ADHD subjects randomized to placebo&#xD;
      treatment. Children will be comprehensively assessed using a variety of clinical and&#xD;
      neuropsychological measures. They will be scanned at baseline while performing both the&#xD;
      go/no-go task (a well validated task for measuring inhibitory control (Durston et al., 2002,&#xD;
      2003)) and the Stay Alert task - a new task designed to measure the arousal component of&#xD;
      attention, which was used successfully in a recent fMRI study of guanfacine in healthy adults&#xD;
      (Clerkin et al., 2009). They will then be treated with GXR or placebo for 6 - 8 weeks in&#xD;
      accordance with titration and dosing strategies used in recent Phase III dose optimization&#xD;
      trials (e.g., up to 4 mg/day), and re-scanned while performing the same two tasks. The fMRI&#xD;
      scans will be conducted using a dedicated research 3.0 T Siemens scanner.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2011</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</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>Go/No-go Task Performance Correct Inhibitions</measure>
    <time_frame>Baseline and 8 weeks</time_frame>
    <description>Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Go/No-go Task Reaction Time</measure>
    <time_frame>Baseline and 8 weeks</time_frame>
    <description>Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Go/No-go Task Performance Correct Responses</measure>
    <time_frame>Baseline and 8 weeks</time_frame>
    <description>Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impressions (CGI-I)</measure>
    <time_frame>up to 8 weeks</time_frame>
    <description>Clinical response was the Clinical Global Impression-Improvement scale (CGI-I). Lower CGI-I scores indicate greater improvement (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6= much worse; 7=very much worse.)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change in Atomoxetine Stimulant Side Effects Rating Scale (ASSERS)</measure>
    <time_frame>up to 8 weeks</time_frame>
    <description>Side effects rating scale. Assesses side effects known to occur in prior research using stimulant and non stimulant medications for treatment of ADHD. Scores range from 0 (not present) to 9 (severe side effects) and have been reported in aggregate as sum of severity responses on highest dose. This number is the sum of ASSERS, meaning it is the number and severity of side effects experienced. The percentage change in score from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Finger Windows</measure>
    <time_frame>Baseline</time_frame>
    <description>Neuropsychological assessment: Finger Windows - a measure of spatial working memory. The participant shows memory of a demonstrated visual pattern. The examiner models a given sequence of windows and ask the participant to imitate the sequence by placing their finger through the same windows in the correct order. The total number of correct sequences achieved determines the level of performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Digit Span</measure>
    <time_frame>Baseline</time_frame>
    <description>Neuropsychological assessment - Digit Span. The Digit Span test is either conducted verbally or using a computer program. A sequence of numbers is shown or read out to the participant. The participant is then told to repeat the numbers that were shown or read to them. This process continues until the participant can no longer remember either the full sequence of numbers or the correct order. This sequence is also continued until the participant makes an error. The Digit Span test is scored by the amount of numbers the participant was able to remember in each test. The scorer must add the total number of correct sequences, backwards and forwards. This test is also scored differently for a range of ages.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHDRS IV)</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>Norm referenced parent interview to assess severity and frequency of ADHD symptoms. Scores are reported as sums 0 (no symptoms) to 54 (severe).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Continuous Performance Test - Commissions</measure>
    <time_frame>Baseline</time_frame>
    <description>Neuropsychological assessment - Continuous Performance Test - Commissions. CPT is a task-oriented computerized assessment of attention-related problems. Scores are compared with the normative scores for the age, group and gender of the person being tested. A t-score of 50 is equal to the mean, with higher values indicating more problematic behaviors and lower scores indicating less problematic behaviors.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>ADHD</condition>
  <condition>Attention Deficit Hyperactivity Disorder</condition>
  <arm_group>
    <arm_group_label>guanfacine hydrochloride XR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Flexible dose titration of guanfacine extended release (Intuniv; active medication). The medication is titrated in doses from 1 - 4 mg once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Flexible dose titration of placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Guanfacine Hydrochloride XR</intervention_name>
    <description>Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose</description>
    <arm_group_label>guanfacine hydrochloride XR</arm_group_label>
    <other_name>INTUNIV non-stimulant medication</other_name>
    <other_name>GXR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose</description>
    <arm_group_label>Placebo Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of any subtype of ADHD&#xD;
&#xD;
          -  Normal findings on physical exam, laboratory studies, vital signs, and ECG&#xD;
&#xD;
          -  Weight = 60 kgs or less&#xD;
&#xD;
          -  Able to complete study procedures and swallow capsules;&#xD;
&#xD;
          -  Willing to commit to the entire visit schedule&#xD;
&#xD;
          -  Off treatment or have been discontinued from their previous medication for two weeks.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Psychiatric comorbidity except Oppositional Defiant Disorder [ODD], Simple Phobia, and&#xD;
             dysthymia (unless ongoing medication treatment is required);&#xD;
&#xD;
          -  Currently a suicide risk, has previously made a suicide attempt or has a prior history&#xD;
             of suicidal behavior;&#xD;
&#xD;
          -  Has failed treatment with an adequate trial of an alpha-2 adrenergic agonist;&#xD;
&#xD;
          -  Known or suspected allergy, hypersensitivity, or clinically significant intolerance to&#xD;
             guanfacine hydrochloride.&#xD;
&#xD;
        Children may not:&#xD;
&#xD;
          -  be treated with systemic medication for a medical or psychiatric illness that have CNS&#xD;
             effects or affect cognitive function;&#xD;
&#xD;
          -  have a known history or presence of structural cardiac abnormalities, exercise-related&#xD;
             cardiac events, or clinically significant bradycardia;&#xD;
&#xD;
          -  have orthostatic hypotension or a known history of hypertension;&#xD;
&#xD;
          -  have an abnormal ECG that is deemed clinically significant;&#xD;
&#xD;
          -  have a history of alcohol or other substance abuse or dependence within the last 6&#xD;
             months;&#xD;
&#xD;
          -  use any medications that affect BP or heart rate (excluding the subject's current ADHD&#xD;
             medication at screening);&#xD;
&#xD;
          -  use another investigational medicinal product or participation in a clinical study&#xD;
             within 30 days prior to the baseline visit;&#xD;
&#xD;
          -  be significantly overweight based on Center for Disease Control and Prevention Body&#xD;
             Mass Index (BMI)-for-age gender specific charts;&#xD;
&#xD;
          -  have body weight of less than 25kg;&#xD;
&#xD;
          -  have a clinically important abnormality on urine drug and alcohol screen (excluding&#xD;
             the subject's current ADHD stimulant, if applicable);&#xD;
&#xD;
          -  be female and currently pregnant or lactating;&#xD;
&#xD;
          -  have symptoms indicative of a primary sleep disorder.&#xD;
&#xD;
          -  have braces or other metal permanently placed within their body.&#xD;
&#xD;
          -  be too anxious to tolerate the fMRI procedure, or be claustrophobic.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>15 Years</maximum_age>
    <healthy_volunteers>No</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>
  <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>
  <results_reference>
    <citation>Bedard AC, Schulz KP, Krone B, Pedraza J, Duhoux S, Halperin JM, Newcorn JH. Neural mechanisms underlying the therapeutic actions of guanfacine treatment in youth with ADHD: a pilot fMRI study. Psychiatry Res. 2015 Mar 30;231(3):353-6. doi: 10.1016/j.pscychresns.2015.01.012. Epub 2015 Jan 19.</citation>
    <PMID>25659477</PMID>
  </results_reference>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <results_first_submitted>March 29, 2017</results_first_submitted>
  <results_first_submitted_qc>January 17, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">February 14, 2018</results_first_posted>
  <last_update_submitted>January 17, 2018</last_update_submitted>
  <last_update_submitted_qc>January 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 14, 2018</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>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Intuniv</keyword>
  <keyword>Attention Deficit Hyperactivity Disorder</keyword>
  <keyword>fMRI</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>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Guanfacine Hydrochloride XR</title>
          <description>Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily</description>
        </group>
        <group group_id="P2">
          <title>Placebo Group</title>
          <description>Flexible dose titration of placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Data unavailable for one participant in each group.</population>
      <group_list>
        <group group_id="B1">
          <title>Guanfacine Hydrochloride XR</title>
          <description>Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily</description>
        </group>
        <group group_id="B2">
          <title>Placebo Group</title>
          <description>Flexible dose titration of placebo</description>
        </group>
        <group group_id="B3">
          <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="12"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="25"/>
          </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="10.6" spread="1.7"/>
                    <measurement group_id="B2" value="11.5" spread="2.5"/>
                    <measurement group_id="B3" value="11.1" spread="2.2"/>
                  </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="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Full Scale IQ</title>
          <description>Full Scale IQ - People who score generally between 70 and 130 are considered to be within the normal range of IQ functioning, where 100 is the theoretical average. Those scoring 130 and above have significantly greater cognitive resources than the average population, and those scoring 70 and below population have significantly fewer cognitive resources.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="110.0" spread="21.6"/>
                    <measurement group_id="B2" value="101.8" spread="13.1"/>
                    <measurement group_id="B3" value="105.7" spread="17.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Attention-Deficit/Hyperactivity Disorder (ADHD) subtype</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Combined</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Inattentive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Comorbid Oppositional Defiant Disorder (ODD)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Clinical Global Impressions - Severity scale (CGI-S)</title>
          <description>Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's symptoms 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 symptoms at the time of rating 1, normal, not at all ill; 2, minimally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, very servely ill.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.9" spread="1.0"/>
                    <measurement group_id="B2" value="5.4" spread="0.9"/>
                    <measurement group_id="B3" value="5.2" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior stimulant treatment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Go/No-go Task Performance Correct Inhibitions</title>
        <description>Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.</description>
        <time_frame>Baseline and 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Guanfacine Hydrochloride XR</title>
            <description>Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Flexible dose titration of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Go/No-go Task Performance Correct Inhibitions</title>
          <description>Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.</description>
          <units>percentage correct inhibitions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Correct inhibitions</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91" spread="8"/>
                    <measurement group_id="O2" value="89" spread="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 Weeks Correct inhibitions</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94" spread="6"/>
                    <measurement group_id="O2" value="92" spread="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Go/No-go Task Reaction Time</title>
        <description>Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.</description>
        <time_frame>Baseline and 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Guanfacine Hydrochloride XR</title>
            <description>Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Flexible dose titration of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Go/No-go Task Reaction Time</title>
          <description>Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.</description>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Reaction time (RT)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="572" spread="144"/>
                    <measurement group_id="O2" value="543" spread="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline Reaction time standard deviation (RTSD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="187" spread="109"/>
                    <measurement group_id="O2" value="165" spread="76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 weeks Reaction time (RT)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="562" spread="106"/>
                    <measurement group_id="O2" value="550" spread="107"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 weeks Reaction time standard deviation (RTSD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="184" spread="93"/>
                    <measurement group_id="O2" value="166" spread="73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Global Impressions (CGI-I)</title>
        <description>Clinical response was the Clinical Global Impression-Improvement scale (CGI-I). Lower CGI-I scores indicate greater improvement (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6= much worse; 7=very much worse.)</description>
        <time_frame>up to 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Guanfacine Hydrochloride XR</title>
            <description>Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Flexible dose titration of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Global Impressions (CGI-I)</title>
          <description>Clinical response was the Clinical Global Impression-Improvement scale (CGI-I). Lower CGI-I scores indicate greater improvement (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6= much worse; 7=very much worse.)</description>
          <units>units 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="12"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="0.7"/>
                    <measurement group_id="O2" value="2.9" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change in Atomoxetine Stimulant Side Effects Rating Scale (ASSERS)</title>
        <description>Side effects rating scale. Assesses side effects known to occur in prior research using stimulant and non stimulant medications for treatment of ADHD. Scores range from 0 (not present) to 9 (severe side effects) and have been reported in aggregate as sum of severity responses on highest dose. This number is the sum of ASSERS, meaning it is the number and severity of side effects experienced. The percentage change in score from baseline.</description>
        <time_frame>up to 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Guanfacine Hydrochloride XR</title>
            <description>Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Flexible dose titration of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change in Atomoxetine Stimulant Side Effects Rating Scale (ASSERS)</title>
          <description>Side effects rating scale. Assesses side effects known to occur in prior research using stimulant and non stimulant medications for treatment of ADHD. Scores range from 0 (not present) to 9 (severe side effects) and have been reported in aggregate as sum of severity responses on highest dose. This number is the sum of ASSERS, meaning it is the number and severity of side effects experienced. The percentage change in score from baseline.</description>
          <units>percentage of mean effects improvement</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78"/>
                    <measurement group_id="O2" value="65.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Finger Windows</title>
        <description>Neuropsychological assessment: Finger Windows - a measure of spatial working memory. The participant shows memory of a demonstrated visual pattern. The examiner models a given sequence of windows and ask the participant to imitate the sequence by placing their finger through the same windows in the correct order. The total number of correct sequences achieved determines the level of performance.</description>
        <time_frame>Baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Guanfacine Hydrochloride XR</title>
            <description>Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Flexible dose titration of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Finger Windows</title>
          <description>Neuropsychological assessment: Finger Windows - a measure of spatial working memory. The participant shows memory of a demonstrated visual pattern. The examiner models a given sequence of windows and ask the participant to imitate the sequence by placing their finger through the same windows in the correct order. The total number of correct sequences achieved determines the level of performance.</description>
          <units>correct sequences</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Finger Windows - F</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.5" spread="6.52"/>
                    <measurement group_id="O2" value="10.75" spread="4.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Finger Windows -B</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.35" spread="5.45"/>
                    <measurement group_id="O2" value="8.00" spread="5.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Digit Span</title>
        <description>Neuropsychological assessment - Digit Span. The Digit Span test is either conducted verbally or using a computer program. A sequence of numbers is shown or read out to the participant. The participant is then told to repeat the numbers that were shown or read to them. This process continues until the participant can no longer remember either the full sequence of numbers or the correct order. This sequence is also continued until the participant makes an error. The Digit Span test is scored by the amount of numbers the participant was able to remember in each test. The scorer must add the total number of correct sequences, backwards and forwards. This test is also scored differently for a range of ages.</description>
        <time_frame>Baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Guanfacine Hydrochloride XR</title>
            <description>Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Flexible dose titration of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Digit Span</title>
          <description>Neuropsychological assessment - Digit Span. The Digit Span test is either conducted verbally or using a computer program. A sequence of numbers is shown or read out to the participant. The participant is then told to repeat the numbers that were shown or read to them. This process continues until the participant can no longer remember either the full sequence of numbers or the correct order. This sequence is also continued until the participant makes an error. The Digit Span test is scored by the amount of numbers the participant was able to remember in each test. The scorer must add the total number of correct sequences, backwards and forwards. This test is also scored differently for a range of ages.</description>
          <units>correct sequences</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Digit Span - F</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.92" spread="1.73"/>
                    <measurement group_id="O2" value="7.54" spread="2.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Digit Span - B</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.62" spread="8.76"/>
                    <measurement group_id="O2" value="48.62" spread="8.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHDRS IV)</title>
        <description>Norm referenced parent interview to assess severity and frequency of ADHD symptoms. Scores are reported as sums 0 (no symptoms) to 54 (severe).</description>
        <time_frame>baseline and 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Guanfacine Hydrochloride XR</title>
            <description>Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Flexible dose titration of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHDRS IV)</title>
          <description>Norm referenced parent interview to assess severity and frequency of ADHD symptoms. Scores are reported as sums 0 (no symptoms) to 54 (severe).</description>
          <units>units 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="12"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.67" spread="9.01"/>
                    <measurement group_id="O2" value="39.15" spread="9.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of treatment at 8 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.42" spread="6.96"/>
                    <measurement group_id="O2" value="22.69" spread="11.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Continuous Performance Test - Commissions</title>
        <description>Neuropsychological assessment - Continuous Performance Test - Commissions. CPT is a task-oriented computerized assessment of attention-related problems. Scores are compared with the normative scores for the age, group and gender of the person being tested. A t-score of 50 is equal to the mean, with higher values indicating more problematic behaviors and lower scores indicating less problematic behaviors.</description>
        <time_frame>Baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Guanfacine Hydrochloride XR</title>
            <description>Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Flexible dose titration of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Continuous Performance Test - Commissions</title>
          <description>Neuropsychological assessment - Continuous Performance Test - Commissions. CPT is a task-oriented computerized assessment of attention-related problems. Scores are compared with the normative scores for the age, group and gender of the person being tested. A t-score of 50 is equal to the mean, with higher values indicating more problematic behaviors and lower scores indicating less problematic behaviors.</description>
          <units>t-scores</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.62" spread="3.81"/>
                    <measurement group_id="O2" value="46.99" spread="2.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Go/No-go Task Performance Correct Responses</title>
        <description>Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.</description>
        <time_frame>Baseline and 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Guanfacine Hydrochloride XR</title>
            <description>Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Flexible dose titration of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Go/No-go Task Performance Correct Responses</title>
          <description>Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.</description>
          <units>percentage correct responses</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Correct responses</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76" spread="18"/>
                    <measurement group_id="O2" value="75" spread="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 Weeks Correct responses</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79" spread="15"/>
                    <measurement group_id="O2" value="74" spread="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Guanfacine Hydrochloride XR</title>
          <description>Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily</description>
        </group>
        <group group_id="E2">
          <title>Placebo Group</title>
          <description>Flexible dose titration of placebo</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="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>ASSERS</default_vocab>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Sleepiness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Difficulty Sleeping</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Dizziness upon standing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Drowsiness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Appearing sedated</sub_title>
                <description>could not tolerate dose rise, dose reduced</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Aggression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Tired</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Weakness</sub_title>
                <description>subjective feeling of weakness, without loss of strength.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Viral Infection</sub_title>
                <description>Sore throat and nasal congestions secondary to common cold</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Increased Anxiety/Panic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Irritable and Moody</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>The small sample size in this pilot study limited power to detect large-sized effects.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Department of Psychiatry</name_or_title>
      <organization>Icahn School of Medicine at Mount Sinai</organization>
      <phone>212-241-6623</phone>
    </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/NCT01709695
org study id: GCO 09-1825
secondary id: HSM:10-00415
nct id: NCT01709695
lead sponsor: 
has dmc: Yes
This study proposes to evaluate the effects of guanfacine extended release on brain
      activation during fMRI in children and adolescents with ADHD between the ages 8-15 and ADHD
      subjects randomized to placebo treatment.

      This study also proposes to collect DNA on study participants, to examine the genetic
      underpinning of the observed fMRI activation profiles at baseline and in response to
      treatment. The purpose is to examine polymorphisms of the adrenergic 2A gene (and other
      related targets) for genetic biomarkers in association with the fMRI findings of this study.
This study proposes to evaluate the effects of guanfacine on brain activation during fMRI in
      12 children and adolescents ages 8 - 15 with ADHD treated with once-daily INTUNIV(TM)
      (guanfacine; GXR) extended release tablets and 12 ADHD subjects randomized to placebo
      treatment. Children will be comprehensively assessed using a variety of clinical and
      neuropsychological measures. They will be scanned at baseline while performing both the
      go/no-go task (a well validated task for measuring inhibitory control (Durston et al., 2002,
      2003)) and the Stay Alert task - a new task designed to measure the arousal component of
      attention, which was used successfully in a recent fMRI study of guanfacine in healthy adults
      (Clerkin et al., 2009). They will then be treated with GXR or placebo for 6 - 8 weeks in
      accordance with titration and dosing strategies used in recent Phase III dose optimization
      trials (e.g., up to 4 mg/day), and re-scanned while performing the same two tasks. The fMRI
      scans will be conducted using a dedicated research 3.0 T Siemens scanner.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Go/No-go Task Performance Correct Inhibitions
time frame: Baseline and 8 weeks
description: Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.
measure: Go/No-go Task Reaction Time
time frame: Baseline and 8 weeks
description: Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.
measure: Go/No-go Task Performance Correct Responses
time frame: Baseline and 8 weeks
description: Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.
measure: Clinical Global Impressions (CGI-I)
time frame: up to 8 weeks
description: Clinical response was the Clinical Global Impression-Improvement scale (CGI-I). Lower CGI-I scores indicate greater improvement (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6= much worse; 7=very much worse.)
measure: Percentage Change in Atomoxetine Stimulant Side Effects Rating Scale (ASSERS)
time frame: up to 8 weeks
description: Side effects rating scale. Assesses side effects known to occur in prior research using stimulant and non stimulant medications for treatment of ADHD. Scores range from 0 (not present) to 9 (severe side effects) and have been reported in aggregate as sum of severity responses on highest dose. This number is the sum of ASSERS, meaning it is the number and severity of side effects experienced. The percentage change in score from baseline.
measure: Finger Windows
time frame: Baseline
description: Neuropsychological assessment: Finger Windows - a measure of spatial working memory. The participant shows memory of a demonstrated visual pattern. The examiner models a given sequence of windows and ask the participant to imitate the sequence by placing their finger through the same windows in the correct order. The total number of correct sequences achieved determines the level of performance.
measure: Digit Span
time frame: Baseline
description: Neuropsychological assessment - Digit Span. The Digit Span test is either conducted verbally or using a computer program. A sequence of numbers is shown or read out to the participant. The participant is then told to repeat the numbers that were shown or read to them. This process continues until the participant can no longer remember either the full sequence of numbers or the correct order. This sequence is also continued until the participant makes an error. The Digit Span test is scored by the amount of numbers the participant was able to remember in each test. The scorer must add the total number of correct sequences, backwards and forwards. This test is also scored differently for a range of ages.
measure: Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHDRS IV)
time frame: baseline and 8 weeks
description: Norm referenced parent interview to assess severity and frequency of ADHD symptoms. Scores are reported as sums 0 (no symptoms) to 54 (severe).
measure: Continuous Performance Test - Commissions
time frame: Baseline
description: Neuropsychological assessment - Continuous Performance Test - Commissions. CPT is a task-oriented computerized assessment of attention-related problems. Scores are compared with the normative scores for the age, group and gender of the person being tested. A t-score of 50 is equal to the mean, with higher values indicating more problematic behaviors and lower scores indicating less problematic behaviors.
arm group label: guanfacine hydrochloride XR
arm group type: Experimental
description: Flexible dose titration of guanfacine extended release (Intuniv; active medication). The medication is titrated in doses from 1 - 4 mg once daily
arm group label: Placebo Group
arm group type: Placebo Comparator
description: Flexible dose titration of placebo
intervention type: Drug
intervention name: Guanfacine Hydrochloride XR
description: Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose
arm group label: guanfacine hydrochloride XR
other name: INTUNIV non-stimulant medication
other name: GXR
intervention type: Drug
intervention name: Placebo
description: Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose
arm group label: Placebo Group
criteria: 
gender: All
minimum age: 8 Years
maximum age: 15 Years
healthy volunteers: No
last name: Jeffrey Newcorn, MD
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
facility: 
country: United States
citation: Bedard AC, Schulz KP, Krone B, Pedraza J, Duhoux S, Halperin JM, Newcorn JH. Neural mechanisms underlying the therapeutic actions of guanfacine treatment in youth with ADHD: a pilot fMRI study. Psychiatry Res. 2015 Mar 30;231(3):353-6. doi: 10.1016/j.pscychresns.2015.01.012. Epub 2015 Jan 19.
PMID: 25659477
responsible party type: Principal Investigator
investigator affiliation: Icahn School of Medicine at Mount Sinai
investigator full name: Jeffrey Newcorn
investigator title: Principal Investigator
mesh term: Hyperkinesis
mesh term: Attention Deficit Disorder with Hyperactivity
mesh term: Guanfacine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The small sample size in this pilot study limited power to detect large-sized effects.
point of contact: 