<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/NCT02247986</url>
  </required_header>
  <id_info>
    <org_study_id>140193</org_study_id>
    <secondary_id>14-M-0193</secondary_id>
    <nct_id>NCT02247986</nct_id>
  </id_info>
  <brief_title>Investigating the Impact of Methylphenidate on Neural Response in Disruptive Behavioral Disorder</brief_title>
  <official_title>Investigating the Impact of Methylphenidate on Neural Response in Disruptive Behavioral Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      - Disruptive behavior is a common problem for children and adolescents. It can be treated&#xD;
      with some success with stimulant medicine. Researchers want to learn more about how this&#xD;
      works.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      - To learn how the brain changes when taking the medicine methylphenidate for behavior&#xD;
      problems.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  Children ages 10 17 with conduct disorder and/or attention deficit disorder.&#xD;
&#xD;
        -  Healthy volunteers the same age.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be screened under a separate protocol.&#xD;
&#xD;
        -  Participants will have two 3-hour sessions at the clinic. Girls who are menstruating&#xD;
           will have a pregnancy test before their scans.&#xD;
&#xD;
        -  Visit 1: All participants will:&#xD;
&#xD;
        -  Perform simple tests on a computer.&#xD;
&#xD;
        -  Fill out a questionnaire along with their parent or guardian.&#xD;
&#xD;
        -  Have an MRI scan. A magnetic field and radio waves take pictures of the brain.&#xD;
           Participants will lie on a table that slides into a metal cylinder. A coil will be&#xD;
           placed over their head. They will be in the scanner for 60 minutes, lying still or&#xD;
           performing a simple task. They will practice the task before the scan. A computer screen&#xD;
           will show them task information during the scan. The scanner makes loud knocking sounds.&#xD;
           Participants will get earplugs. Their parent or guardian can stay with them during the&#xD;
           scan.&#xD;
&#xD;
        -  Only participants with behavior disorders will:&#xD;
&#xD;
        -  Take a pill of the study medicine or placebo.&#xD;
&#xD;
        -  Be monitored for any side effects.&#xD;
&#xD;
        -  Visit 2 is a repeat of Visit 1, except participants who got a pill in Visit 1 will get&#xD;
           the other pill in Visit 2. For healthy volunteers, the 2 visits are exactly the same.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OBJECTIVE:&#xD;
&#xD;
      To determine the impact, as indexed by BOLD response, of the administration of dopaminergic&#xD;
      agonist (methylphenidate) on the pathophysiology of CD/ODD.&#xD;
&#xD;
      STUDY POPULATION:&#xD;
&#xD;
      Youth with CD/ODD and typically developing (TD) youth.&#xD;
&#xD;
      DESIGN:&#xD;
&#xD;
      The study will involve a 2 session design (methylphenidate [MPH] vs. placebo). Patients with&#xD;
      CD/ODD will participate in both sessions. TD youth will be tested for 2 sessions (no&#xD;
      medication) to provide an index of typical task response. Activity within regions of interest&#xD;
      identified from the TD youth will be used to determine whether MPH reduces differences in&#xD;
      BOLD response in CD/ODD relative to TD youth. ICU scores and current ADHD symptomatology will&#xD;
      be used as covariates to determine whether these variables moderate the putative increase in&#xD;
      BOLD response in target regions in the patients with CD.&#xD;
&#xD;
      OUTCOME MEASURES:&#xD;
&#xD;
      Principle dependent measures will be BOLD responses as measured through core tasks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <start_date>September 4, 2014</start_date>
  <completion_date type="Actual">May 18, 2015</completion_date>
  <primary_completion_date type="Actual">May 18, 2015</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Patients with CD will show an increase in the amygdala response to fearful expressions such that the difference between BOLD response in patients and TDs is reduced on MPH relative to placebo. ICU score will be a significant covariate of the inc...</measure>
    <time_frame>2 years from the initiation of the protocol</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Patients with CD will show an increase in reward prediction errors and reward expected value signaling within striatum and ventromedial frontal cortex (vmPFC) such that the difference between BOLD response in patients and TDs is reduced on MPH r...</measure>
    <time_frame>2 years from the initiation of the protocol</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Patients with CD will show an increase in conflict related signaling within dorsomedial, lateral and parietal cortices such that the difference between BOLD response in patients and TDs is reduced on MPH relative to placebo. Current ADHD sympto...</measure>
    <time_frame>2 years from the initiation of the protocol</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Symptom profiles measured by the clinical scales listed in the protocol (CBCL, the ICU, Connor s parent report on ADHD symptom) will be significantly related to the BOLD signal changes after methylphenidate administration.</measure>
    <time_frame>2 years from the initiation of the protocol</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">0</enrollment>
  <condition>Conduct Disorder</condition>
  <condition>Attention Defict Hyperactivity Disorder</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylphenidate Hydrochloride</intervention_name>
    <description>Bold signal changes by methylphenidate on DBD</description>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA&#xD;
&#xD;
        Youth with CD&#xD;
&#xD;
          1. 10-17 years of age.&#xD;
&#xD;
          2. A current diagnosis of CD as determined by the Kiddie-SADS, lifetime version.&#xD;
&#xD;
               -  Youth in the CD+comorbid ADHD group will also meet diagnostic criteria for ADHD.&#xD;
&#xD;
               -  Youth in the CD without comorbid ADHD group will specifically not meet diagnostic&#xD;
                  criteria for ADHD.&#xD;
&#xD;
          3. Youth with CD shouldmust be na(SqrRoot) ve to psychoactive medication (such as:&#xD;
             methylphenidate and amphetamine).&#xD;
&#xD;
        TD youth&#xD;
&#xD;
          1. 10-17 years of age.&#xD;
&#xD;
          2. No current psychiatric diagnosis, as determined by the Kiddie-SADS, lifetime version.&#xD;
&#xD;
        EXCLUSION CRITERIA&#xD;
&#xD;
        Exclusion criteria for youth with CD (with or without ADHD)&#xD;
&#xD;
          1. Comorbid psychotic, major mood, tic, pervasive developmental, and substance abuse&#xD;
             disorders.&#xD;
&#xD;
          2. Presence of comorbid ADHD is exclusory for the group of patients with CD without ADHD&#xD;
&#xD;
          3. History of known structural cardiac abnormalities, cardiomyopathy, serious heart&#xD;
             rhythm abnormalities, coronary artery disease, or other serious cardiac problems&#xD;
&#xD;
          4. Current weight less than 25kg or over 90kg&#xD;
&#xD;
        Exclusion criteria for all participants (CD with ADHD, CD without ADHD and TD)&#xD;
&#xD;
          1. History of serious CNS disease disorder (examples aresuch as: history of seizure,&#xD;
             epilepsy, brain tumor, brain hemorrhage, and major CNS infection such as meningitis or&#xD;
             encephalitis)&#xD;
&#xD;
          2. Previous history of known structural cardiac abnormalities, cardiomyopathy, serious&#xD;
             heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems&#xD;
&#xD;
          3. Current use of any psychiatric medications and centrally acting medications (such as&#xD;
             stimulants, non-stimulant ADHD medications, antidepressants, anxiolytics,&#xD;
             antipsychotics and anti-epilepsy medications), and past history of use of psychoactive&#xD;
             medication (such as methylphenidate and amphetamine)&#xD;
&#xD;
          4. A positive urine pregnancy test&#xD;
&#xD;
          5. A Positive urine toxicology, History/current diagnosis of substance abuse/dependence&#xD;
&#xD;
          6. Suicidal or homicidal ideation within the past 6 months.&#xD;
&#xD;
          7. Wechsler Abbreviated Scale of Intelligence (WASI) (D. Wechsler, 1999) scores &lt;70&#xD;
&#xD;
          8. Metal in body (i.e., hearing aid, cardiac pacemaker, bone plates, etc),&#xD;
             claustrophobia, or any other condition that would preclude fMRI scanning.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James J Blair, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Mental Health (NIMH)</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <reference>
    <citation>Waschbusch DA, Carrey NJ, Willoughby MT, King S, Andrade BF. Effects of methylphenidate and behavior modification on the social and academic behavior of children with disruptive behavior disorders: the moderating role of callous/unemotional traits. J Clin Child Adolesc Psychol. 2007 Oct-Dec;36(4):629-44. doi: 10.1080/15374410701662766.</citation>
    <PMID>18088220</PMID>
  </reference>
  <reference>
    <citation>Blair RJ. Neurocognitive models of aggression, the antisocial personality disorders, and psychopathy. J Neurol Neurosurg Psychiatry. 2001 Dec;71(6):727-31. doi: 10.1136/jnnp.71.6.727.</citation>
    <PMID>11723191</PMID>
  </reference>
  <reference>
    <citation>White SF, Pope K, Sinclair S, Fowler KA, Brislin SJ, Williams WC, Pine DS, Blair RJ. Disrupted expected value and prediction error signaling in youths with disruptive behavior disorders during a passive avoidance task. Am J Psychiatry. 2013 Mar;170(3):315-23. doi: 10.1176/appi.ajp.2012.12060840.</citation>
    <PMID>23450288</PMID>
  </reference>
  <verification_date>May 18, 2015</verification_date>
  <study_first_submitted>September 20, 2014</study_first_submitted>
  <study_first_submitted_qc>September 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>November 30, 2019</last_update_submitted>
  <last_update_submitted_qc>November 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Conduct Disorder</keyword>
  <keyword>Methylphenidate</keyword>
  <keyword>Disruptive Behavior Disorders</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Conduct Disorder</mesh_term>
    <mesh_term>Attention Deficit and Disruptive Behavior Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylphenidate</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02247986
org study id: 140193
secondary id: 14-M-0193
nct id: NCT02247986
lead sponsor: 
Background:

      - Disruptive behavior is a common problem for children and adolescents. It can be treated
      with some success with stimulant medicine. Researchers want to learn more about how this
      works.

      Objective:

      - To learn how the brain changes when taking the medicine methylphenidate for behavior
      problems.

      Eligibility:

        -  Children ages 10 17 with conduct disorder and/or attention deficit disorder.

        -  Healthy volunteers the same age.

      Design:

        -  Participants will be screened under a separate protocol.

        -  Participants will have two 3-hour sessions at the clinic. Girls who are menstruating
           will have a pregnancy test before their scans.

        -  Visit 1: All participants will:

        -  Perform simple tests on a computer.

        -  Fill out a questionnaire along with their parent or guardian.

        -  Have an MRI scan. A magnetic field and radio waves take pictures of the brain.
           Participants will lie on a table that slides into a metal cylinder. A coil will be
           placed over their head. They will be in the scanner for 60 minutes, lying still or
           performing a simple task. They will practice the task before the scan. A computer screen
           will show them task information during the scan. The scanner makes loud knocking sounds.
           Participants will get earplugs. Their parent or guardian can stay with them during the
           scan.

        -  Only participants with behavior disorders will:

        -  Take a pill of the study medicine or placebo.

        -  Be monitored for any side effects.

        -  Visit 2 is a repeat of Visit 1, except participants who got a pill in Visit 1 will get
           the other pill in Visit 2. For healthy volunteers, the 2 visits are exactly the same.
OBJECTIVE:

      To determine the impact, as indexed by BOLD response, of the administration of dopaminergic
      agonist (methylphenidate) on the pathophysiology of CD/ODD.

      STUDY POPULATION:

      Youth with CD/ODD and typically developing (TD) youth.

      DESIGN:

      The study will involve a 2 session design (methylphenidate [MPH] vs. placebo). Patients with
      CD/ODD will participate in both sessions. TD youth will be tested for 2 sessions (no
      medication) to provide an index of typical task response. Activity within regions of interest
      identified from the TD youth will be used to determine whether MPH reduces differences in
      BOLD response in CD/ODD relative to TD youth. ICU scores and current ADHD symptomatology will
      be used as covariates to determine whether these variables moderate the putative increase in
      BOLD response in target regions in the patients with CD.

      OUTCOME MEASURES:

      Principle dependent measures will be BOLD responses as measured through core tasks.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Patients with CD will show an increase in the amygdala response to fearful expressions such that the difference between BOLD response in patients and TDs is reduced on MPH relative to placebo. ICU score will be a significant covariate of the inc...
time frame: 2 years from the initiation of the protocol
measure: Patients with CD will show an increase in reward prediction errors and reward expected value signaling within striatum and ventromedial frontal cortex (vmPFC) such that the difference between BOLD response in patients and TDs is reduced on MPH r...
time frame: 2 years from the initiation of the protocol
measure: Patients with CD will show an increase in conflict related signaling within dorsomedial, lateral and parietal cortices such that the difference between BOLD response in patients and TDs is reduced on MPH relative to placebo. Current ADHD sympto...
time frame: 2 years from the initiation of the protocol
measure: Symptom profiles measured by the clinical scales listed in the protocol (CBCL, the ICU, Connor s parent report on ADHD symptom) will be significantly related to the BOLD signal changes after methylphenidate administration.
time frame: 2 years from the initiation of the protocol
intervention type: Drug
intervention name: Methylphenidate Hydrochloride
description: Bold signal changes by methylphenidate on DBD
criteria: 
gender: All
minimum age: 10 Years
maximum age: 17 Years
healthy volunteers: No
last name: James J Blair, Ph.D.
role: Principal Investigator
affiliation: National Institute of Mental Health (NIMH)
country: United States
citation: Waschbusch DA, Carrey NJ, Willoughby MT, King S, Andrade BF. Effects of methylphenidate and behavior modification on the social and academic behavior of children with disruptive behavior disorders: the moderating role of callous/unemotional traits. J Clin Child Adolesc Psychol. 2007 Oct-Dec;36(4):629-44. doi: 10.1080/15374410701662766.
PMID: 18088220
citation: Blair RJ. Neurocognitive models of aggression, the antisocial personality disorders, and psychopathy. J Neurol Neurosurg Psychiatry. 2001 Dec;71(6):727-31. doi: 10.1136/jnnp.71.6.727.
PMID: 11723191
citation: White SF, Pope K, Sinclair S, Fowler KA, Brislin SJ, Williams WC, Pine DS, Blair RJ. Disrupted expected value and prediction error signaling in youths with disruptive behavior disorders during a passive avoidance task. Am J Psychiatry. 2013 Mar;170(3):315-23. doi: 10.1176/appi.ajp.2012.12060840.
PMID: 23450288
responsible party type: Sponsor
mesh term: Conduct Disorder
mesh term: Attention Deficit and Disruptive Behavior Disorders
mesh term: Methylphenidate