xml: <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/NCT05974241</url>
    </required_header>
    <id_info>
      <org_study_id>TSGH-C106-103</org_study_id>
      <nct_id>NCT05974241</nct_id>
    </id_info>
    <brief_title>Irritability in Children With ADHD and Emotion Dysregulation</brief_title>
    <official_title>Irritability in Children With ADHD and Emotion Dysregulation: Clinical Profiles, Neuropsychological Characteristics , and Pharmacological Treatment: A Cross-over Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tri-Service General Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Tri-Service General Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Objective:&#xD;
  &#xD;
        Emotion dysregulation is common among children with ADHD and associated with a broad range of&#xD;
        adult psychopathology, which is similar to the longitudinal outcomes of childhood&#xD;
        irritability. However, the profiles of irritability in children with ADHD and emotion&#xD;
        dysregulation has been understudied. This study aimed to investigate the efficacy of&#xD;
        methylphenidate and aripiprazole in the treatment of irritability in children with ADHD and&#xD;
        emotion dysregulation. In addition, the clinical profiles and neuropsychological&#xD;
        characteristics of irritability in children with ADHD were explored.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Methods:&#xD;
  &#xD;
        A three-step, open-label, 10 week pilot study was conducted. Methylphenidate (4 weeks),&#xD;
        aripiprazole (4 weeks), and the combination (2weeks) were examined in sequence as the&#xD;
        treatment for irritability in children with ADHD and emotion dysregulation, defined by the&#xD;
        CBCL-Dysregulation Profile. The primary outcome was improvement of irritability as measured&#xD;
        by Aberrant Behavior Checklist-irritability subscale (ABC-I). During the first step, the&#xD;
        subjects received pharmacological treatment of methylphenidate with flexible dosage for 4&#xD;
        weeks. Those subjects who had suboptimal response to methylphenidate (reduction of ABC-I&#xD;
        score &lt; 25%) entered the second step and the medication was switched to aripiprazole. After 4&#xD;
        weeks of treatment, those whose ABC-I scores reduced &lt; 25% entered the third step and&#xD;
        received the treatment of combination of methylphenidate and aripiprazole for two weeks (3rd&#xD;
        step).&#xD;
  &#xD;
        Clinical profiles of irritability were evaluated with the Affective Reactivity Index (ARI),&#xD;
        the Strengths and Difficulties Questionnaire, the Social Adjustment Inventory for Children&#xD;
        and Adolescents, and the Autism Behavior Checklist-Taiwan Version. The neurophysiological&#xD;
        characteristics of the subjects were assessed by three Cantab subtests: Emotion Recognition&#xD;
        Task, One Touch Stockings of Cambridge, and Spatial Working Memory. The aforementioned&#xD;
        measurements were administered at baseline and at the end of each step.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">April 21, 2017</start_date>
    <completion_date type="Actual">April 7, 2022</completion_date>
    <primary_completion_date type="Actual">April 7, 2022</primary_completion_date>
    <phase>Phase 4</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <intervention_model_description>A three-step, open-label, 10 week pilot study</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Aberrant Behavior Checklist-irritability subscale (ABC-I)</measure>
      <time_frame>4 weeks for the 1st step, 4 weeks for the 2nd step, and 2 weeks for the 3rd step</time_frame>
      <description>The ABC is an instrument developed to assess emotional and behavioral difficulties in individuals with developmental disabilities. However, its irritability subscale (ABC-I) is a proven well-validated and widely used rating inventory for measuring irritability in neurotypical children. This subscale consists of 15 items about irritability, aggression, tantrums, agitation, and unstable mood.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Affective Reactivity Index (ARI)</measure>
      <time_frame>4 weeks for the 1st step, 4 weeks for the 2nd step, and 2 weeks for the 3rd step</time_frame>
      <description>The ARI was created as a dimensional measurement of irritability with both parent-report and self-report form. This questionnaire, assessing for symptoms of irritability in the previous 6 months, is composed of 6 items, and the 7th item on functional impairment is rated on a three-point scale (ranging from 0 for &quot;not true&quot; to 2 for &quot;certainly true&quot;). The reliability and validity of the ARI in typically developed children has been previously reported. The sum of scores of the first six items was used in this present study.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Social Adjustment Inventory for Children and Adolescents (SAICA)</measure>
      <time_frame>4 weeks for the 1st step, 4 weeks for the 2nd step, and 2 weeks for the 3rd step</time_frame>
      <description>The SAICA was designed for children and adolescents aged 6-18 years, and provided a systematic evaluation of children's and adolescents' adaptive functioning. It assessed social adjustment in four major role areas: school, spare-time activities, peer relations, and home life. The scoring of each item ranges from 1 for positive/not a problem, to 4 for negative/severe problem. The children or adolescents with higher scores had either poorer functioning or more severe problems in the assessed domain.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The Strengths and Difficulties Questionnaire (SDQ)</measure>
      <time_frame>4 weeks for the 1st step, 4 weeks for the 2nd step, and 2 weeks for the 3rd step</time_frame>
      <description>The SDQ is a questionnaire for assessing the psychological problems and strengths in children, consisting of 25 items categorized as 5 subscales based on factor analyses: emotional symptoms, conduct problems, hyperactivity, peer problems, and prosocial behavior. An impact supplement added to the SDQ provides additional information on the target child's possible difficulties and the burden for others. Previous studies report that the Chinese version of the SDQ is a reliable and valid instrument for clinical studies in Taiwan.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cantab subtest-- Emotion Recognition Task (ERT)</measure>
      <time_frame>4 weeks for the 1st step, 4 weeks for the 2nd step, and 2 weeks for the 3rd step</time_frame>
      <description>The outcome measures for ERT cover percentage and number correct or incorrect and overall response latencies, which can be looked at either across individual emotions or across all emotions at once.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cantab subtest-- One Touch Stockings of Cambridge (OTS)</measure>
      <time_frame>4 weeks for the 1st step, 4 weeks for the 2nd step, and 2 weeks for the 3rd step</time_frame>
      <description>Outcome measures include the number of problems solved on first choice, mean choices to correct, mean latency (speed of response) to first choice and mean latency to correct. Each of these measures may be calculated for all problems, or for problems with a specified number of moves (one-move to five or six moves).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cantab subtest-- Spatial Working Memory (SWM)</measure>
      <time_frame>4 weeks for the 1st step, 4 weeks for the 2nd step, and 2 weeks for the 3rd step</time_frame>
      <description>Outcome measures include errors (selecting boxes that have already been found to be empty and revisiting boxes which have already been found to contain a token) and strategy.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Actual">36</enrollment>
    <condition>Irritable Mood</condition>
    <condition>ADHD</condition>
    <arm_group>
      <arm_group_label>Pharmacological treatment</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>During the first step, the subjects received pharmacological treatment of methylphenidate with flexible dosage for 4 weeks. Those subjects who had suboptimal response to methylphenidate entered the second step with aripiprazole. After 4 weeks of treatment, those had suboptimal response to aripiprazole entered the third step and received the treatment of combination of methylphenidate and aripiprazole for two weeks (3rd step).</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Methylphenidate, aripiprazole, and combination</intervention_name>
      <description>Methylphenidate (4 weeks), aripiprazole (4 weeks), and the combination (2weeks). The primary outcome was improvement of irritability as measured by Aberrant Behavior Checklist-irritability subscale (ABC-I). During the first step, the subjects received pharmacological treatment of methylphenidate with flexible dosage for 4 weeks. Those subjects who had suboptimal response to methylphenidate (reduction of ABC-I score &lt; 25%) entered the second step and the medication was switched to aripiprazole. After 4 weeks of treatment, those whose ABC-I scores reduced &lt; 25% entered the third step and received the treatment of combination of methylphenidate and aripiprazole for two weeks (3rd step).</description>
      <arm_group_label>Pharmacological treatment</arm_group_label>
      <other_name>Ritalin/Concerta, Abilify, and combination</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients aged 6 to 18 who have ADHD and emotion dysregulation, defined by the&#xD;
               CBCL-Dysregulation Profile.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients who are not willing to participate in the study after detailed explanation.&#xD;
  &#xD;
            -  Patients who have intellectual disability or could not follow the investigator's&#xD;
               instructions.&#xD;
  &#xD;
            -  Patients who have severe neurological or mental illness like epileptic disorder,&#xD;
               schizophrenia, bipolar disorder, or uncontrolled suicide risk.&#xD;
  &#xD;
            -  Patients who have severe medical illness or surgical conditions like uncontrolled&#xD;
               abnormal thyroid function, or severe congenital heart disease.&#xD;
  &#xD;
            -  Patients who are allergic to methylphenidate or aripiprazole.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>6 Years</minimum_age>
      <maximum_age>18 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Chin-Bin Yeh, MD., PhD.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Tri-Service General Hospital</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Tri-Service General Hospital, National Defense Medical Center</name>
        <address>
          <city>Taipei</city>
          <zip>114</zip>
          <country>Taiwan</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Taiwan</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 26, 2023</study_first_submitted>
    <study_first_submitted_qc>July 26, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>August 4, 2023</last_update_submitted>
    <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Tri-Service General Hospital</investigator_affiliation>
      <investigator_full_name>Chin-Bin Yeh, MD, PhD</investigator_full_name>
      <investigator_title>Attending Physician</investigator_title>
    </responsible_party>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Aripiprazole</mesh_term>
      <mesh_term>Methylphenidate</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05974241
  org study id: TSGH-C106-103
  nct id: NCT05974241
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Objective:
  
        Emotion dysregulation is common among children with ADHD and associated with a broad range of
        adult psychopathology, which is similar to the longitudinal outcomes of childhood
        irritability. However, the profiles of irritability in children with ADHD and emotion
        dysregulation has been understudied. This study aimed to investigate the efficacy of
        methylphenidate and aripiprazole in the treatment of irritability in children with ADHD and
        emotion dysregulation. In addition, the clinical profiles and neuropsychological
        characteristics of irritability in children with ADHD were explored.
  Methods:
  
        A three-step, open-label, 10 week pilot study was conducted. Methylphenidate (4 weeks),
        aripiprazole (4 weeks), and the combination (2weeks) were examined in sequence as the
        treatment for irritability in children with ADHD and emotion dysregulation, defined by the
        CBCL-Dysregulation Profile. The primary outcome was improvement of irritability as measured
        by Aberrant Behavior Checklist-irritability subscale (ABC-I). During the first step, the
        subjects received pharmacological treatment of methylphenidate with flexible dosage for 4
        weeks. Those subjects who had suboptimal response to methylphenidate (reduction of ABC-I
        score < 25%) entered the second step and the medication was switched to aripiprazole. After 4
        weeks of treatment, those whose ABC-I scores reduced < 25% entered the third step and
        received the treatment of combination of methylphenidate and aripiprazole for two weeks (3rd
        step).
  
        Clinical profiles of irritability were evaluated with the Affective Reactivity Index (ARI),
        the Strengths and Difficulties Questionnaire, the Social Adjustment Inventory for Children
        and Adolescents, and the Autism Behavior Checklist-Taiwan Version. The neurophysiological
        characteristics of the subjects were assessed by three Cantab subtests: Emotion Recognition
        Task, One Touch Stockings of Cambridge, and Spatial Working Memory. The aforementioned
        measurements were administered at baseline and at the end of each step.
  allocation: N/A
  intervention model: Sequential Assignment
  intervention model description: A three-step, open-label, 10 week pilot study
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Aberrant Behavior Checklist-irritability subscale (ABC-I)
  time frame: 4 weeks for the 1st step, 4 weeks for the 2nd step, and 2 weeks for the 3rd step
  description: The ABC is an instrument developed to assess emotional and behavioral difficulties in individuals with developmental disabilities. However, its irritability subscale (ABC-I) is a proven well-validated and widely used rating inventory for measuring irritability in neurotypical children. This subscale consists of 15 items about irritability, aggression, tantrums, agitation, and unstable mood.
  measure: Affective Reactivity Index (ARI)
  time frame: 4 weeks for the 1st step, 4 weeks for the 2nd step, and 2 weeks for the 3rd step
  description: The ARI was created as a dimensional measurement of irritability with both parent-report and self-report form. This questionnaire, assessing for symptoms of irritability in the previous 6 months, is composed of 6 items, and the 7th item on functional impairment is rated on a three-point scale (ranging from 0 for "not true" to 2 for "certainly true"). The reliability and validity of the ARI in typically developed children has been previously reported. The sum of scores of the first six items was used in this present study.
  measure: Social Adjustment Inventory for Children and Adolescents (SAICA)
  time frame: 4 weeks for the 1st step, 4 weeks for the 2nd step, and 2 weeks for the 3rd step
  description: The SAICA was designed for children and adolescents aged 6-18 years, and provided a systematic evaluation of children's and adolescents' adaptive functioning. It assessed social adjustment in four major role areas: school, spare-time activities, peer relations, and home life. The scoring of each item ranges from 1 for positive/not a problem, to 4 for negative/severe problem. The children or adolescents with higher scores had either poorer functioning or more severe problems in the assessed domain.
  measure: The Strengths and Difficulties Questionnaire (SDQ)
  time frame: 4 weeks for the 1st step, 4 weeks for the 2nd step, and 2 weeks for the 3rd step
  description: The SDQ is a questionnaire for assessing the psychological problems and strengths in children, consisting of 25 items categorized as 5 subscales based on factor analyses: emotional symptoms, conduct problems, hyperactivity, peer problems, and prosocial behavior. An impact supplement added to the SDQ provides additional information on the target child's possible difficulties and the burden for others. Previous studies report that the Chinese version of the SDQ is a reliable and valid instrument for clinical studies in Taiwan.
  measure: Cantab subtest-- Emotion Recognition Task (ERT)
  time frame: 4 weeks for the 1st step, 4 weeks for the 2nd step, and 2 weeks for the 3rd step
  description: The outcome measures for ERT cover percentage and number correct or incorrect and overall response latencies, which can be looked at either across individual emotions or across all emotions at once.
  measure: Cantab subtest-- One Touch Stockings of Cambridge (OTS)
  time frame: 4 weeks for the 1st step, 4 weeks for the 2nd step, and 2 weeks for the 3rd step
  description: Outcome measures include the number of problems solved on first choice, mean choices to correct, mean latency (speed of response) to first choice and mean latency to correct. Each of these measures may be calculated for all problems, or for problems with a specified number of moves (one-move to five or six moves).
  measure: Cantab subtest-- Spatial Working Memory (SWM)
  time frame: 4 weeks for the 1st step, 4 weeks for the 2nd step, and 2 weeks for the 3rd step
  description: Outcome measures include errors (selecting boxes that have already been found to be empty and revisiting boxes which have already been found to contain a token) and strategy.
  arm group label: Pharmacological treatment
  arm group type: Experimental
  description: During the first step, the subjects received pharmacological treatment of methylphenidate with flexible dosage for 4 weeks. Those subjects who had suboptimal response to methylphenidate entered the second step with aripiprazole. After 4 weeks of treatment, those had suboptimal response to aripiprazole entered the third step and received the treatment of combination of methylphenidate and aripiprazole for two weeks (3rd step).
  intervention type: Drug
  intervention name: Methylphenidate, aripiprazole, and combination
  description: Methylphenidate (4 weeks), aripiprazole (4 weeks), and the combination (2weeks). The primary outcome was improvement of irritability as measured by Aberrant Behavior Checklist-irritability subscale (ABC-I). During the first step, the subjects received pharmacological treatment of methylphenidate with flexible dosage for 4 weeks. Those subjects who had suboptimal response to methylphenidate (reduction of ABC-I score < 25%) entered the second step and the medication was switched to aripiprazole. After 4 weeks of treatment, those whose ABC-I scores reduced < 25% entered the third step and received the treatment of combination of methylphenidate and aripiprazole for two weeks (3rd step).
  arm group label: Pharmacological treatment
  other name: Ritalin/Concerta, Abilify, and combination
  criteria: 
  gender: All
  minimum age: 6 Years
  maximum age: 18 Years
  healthy volunteers: No
  last name: Chin-Bin Yeh, MD., PhD.
  role: Principal Investigator
  affiliation: Tri-Service General Hospital
  facility: 
  country: Taiwan
  responsible party type: Principal Investigator
  investigator affiliation: Tri-Service General Hospital
  investigator full name: Chin-Bin Yeh, MD, PhD
  investigator title: Attending Physician
  mesh term: Aripiprazole
  mesh term: Methylphenidate