<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/NCT02184598</url>
  </required_header>
  <id_info>
    <org_study_id>125002</org_study_id>
    <nct_id>NCT02184598</nct_id>
  </id_info>
  <brief_title>Randomized Controlled Trial With Use of Cognitive Training in Children and Adolescents With ADHD</brief_title>
  <official_title>Randomized Controlled Trial With Use of Cognitive Training in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital de Clinicas de Porto Alegre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital de Clinicas de Porto Alegre</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Purpose: This project assess the effectiveness of a cognitive training as an add-on&#xD;
      intervention to drug treatment in children and adolescents diagnosed with&#xD;
      Attention-Deficit/Hyperactivity Disorder (ADHD) compared to a placebo training. The cognitive&#xD;
      training consists of 6 computerized games that are based on principles of neuroplastic&#xD;
      change.&#xD;
&#xD;
      ADHD: current treatment - International clinical guidelines indicate that pharmacological&#xD;
      interventions in particular stimulants are the first-line treatment for ADHD. However, about&#xD;
      30% of children affected by the disorder do not respond to medication alone, exhibit partial&#xD;
      response or can not tolerate the adverse effects. In addition there is a group of parents who&#xD;
      do not accept the use of medication for the treatment of ADHD in their children. In recent&#xD;
      years cognitive training has received considerable attention as a treatment to ADHD. The&#xD;
      evidence base for cognitive training programs are still forming with few randomized&#xD;
      placebo-controlled studies. However, this approach seems to be effective either as a&#xD;
      treatment for ADHD - and others cognitive disorders in childhood - or as a tool to enhance&#xD;
      cognitive ability and school performance in children and adults. No previous study has&#xD;
      evaluated this cognitive intervention in a clinical trial with placebo-controlled&#xD;
      intervention and as an adjunctive treatment to medication. Additionally, the investigators&#xD;
      will assess brain changes associated with this intervention using neuroimaging (fMRI).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Material and Methods Trial design Randomized clinical trial with placebo control. This study&#xD;
      will compare the cognitive training program versus the placebo condition to assess the&#xD;
      reduction on residual symptoms, the improvement in the neurocognitive function and brain&#xD;
      activation changes in children and adolescents with ADHD receiving stimulants. Sixty&#xD;
      subjects, six to thirteen years-old with ADHD confirmed by the Kiddie Schedule for Affective&#xD;
      Disorders and Schizophrenia (K-SADS) will be randomly assigned to 12 weeks of cognitive or&#xD;
      placebo training.&#xD;
&#xD;
      Participants To be included in the study children and adolescent need to meet the following&#xD;
      criteria (a) age between 6-13 years, (b) a diagnosis of ADHD classified according to the&#xD;
      criteria of the Diagnostic and Statistical Manual of Mental Disorders (5th edition), (c)&#xD;
      medicated and stabilized with psychostimulants but partially restored - inattention SNAP&#xD;
      score (mean scores of parents and teachers &gt; or = 1), (d) a full scale intelligence quotient&#xD;
      (IQ) of at least 80, (e) access to a computer with windows vista 7 and speakers, and access&#xD;
      to internet. Participants will be excluded in case (a) another comorbid psychiatry diagnosis&#xD;
      clinically significant and requiring treatment at the time of enter in the study protocol.&#xD;
&#xD;
      Sample Size Calculation There was no previous study that used the design proposed in this&#xD;
      investigation. Considering a reduction 20% higher of the SNAP-IV scores in the active group&#xD;
      intervention (stimulants + cognitive training), sample size in both groups of 27 participants&#xD;
      and standard-deviation in the magnitude of half of the medium score in each group (moderate&#xD;
      variability), the study will be able to detect a moderate effect size (ES = 0,4). Calculating&#xD;
      a sample loss of 10% each group, we define a sample size per group of 30 individuals.&#xD;
&#xD;
      Cognitive intervention protocol:&#xD;
&#xD;
      A portuguese version of the new Cognitive Computerized Training was created with the&#xD;
      partnership of Yale University research team.&#xD;
&#xD;
      The cognitive training program is composed by computerized exercises with six different games&#xD;
      divided in multiples levels and sublevels with increasing difficulty. During the games,&#xD;
      several neuropsychological domains are required from the participant such working memory,&#xD;
      sustained attention, response inhibition and others. In each session the participant will&#xD;
      play 6 games divided in 5 minutes blocks. The aim of these games is to engage and activate&#xD;
      targeted neurocognitive systems This protocol will be run in schools. It will be consisted of&#xD;
      4 times/week sessions (3 times at school and 1 time at home) for 12 weeks with 30 min of&#xD;
      duration.&#xD;
&#xD;
      The placebo cognitive training (control group) will contain the same exposure time of the&#xD;
      active group but without any element regarding to the cognitive training.&#xD;
&#xD;
      Pharmacological protocol All subjects must be receiving pharmacological treatment for ADHD&#xD;
      with a stable dose of stimulants for at least 1 month in doses not inferior of 0.3mg/kg/per&#xD;
      day of methylphenidate or 30mg/per day of lisdexamphetamine. Any increase in doses during the&#xD;
      protocol will be permitted.&#xD;
&#xD;
      Neuropsychological protocol An assessment before the beginning of the intervention and&#xD;
      pos-treatment will be done by a trained neuropsychologist using three tests of a NIH toolbox&#xD;
      (C8Kids platform): Flanker Test, Go/NoGo Test and List Sorting Test of Working Memory and a&#xD;
      neuropsychological battery created by our team using six tests: CPT II (Conner´s Continuous&#xD;
      Performance Test II), Digit Span, Spatial Span, Reaction Time Task, Trail Making Test and&#xD;
      Picture Concepts.&#xD;
&#xD;
      Neuroimaging protocol A subgroup of 10 participants from each group will be drawn to a&#xD;
      functional resonance exam (MRIf) before and immediately after the cognitive or placebo&#xD;
      training. During the exam they will do a neuropsychological tests ( Go/NoGo; N-Back - working&#xD;
      memory - and SAT - sustained attention test).&#xD;
&#xD;
      Statistical methods Statistical analyses will be performed with Statistical Package for the&#xD;
      Social Sciences (SPSS) 12.0. The univariate analyses will be performed with the t student&#xD;
      test / Mann-Whitney to continuous variables or Chi-Square test (X²) / Fischer test to&#xD;
      categorical variables. The variables that present relationship with the outcomes will be&#xD;
      maintained in multivariate models. The effective of the intervention over time will be assess&#xD;
      through analyses of mixed models.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date>July 2014</start_date>
  <completion_date type="Anticipated">December 2016</completion_date>
  <primary_completion_date type="Anticipated">July 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in ADHD symptomatology</measure>
    <time_frame>Baseline; 12 weeks.</time_frame>
    <description>Measured by the SNAP scale filled by parents and teachers.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in neuropsychological function.</measure>
    <time_frame>Baseline; 12 weeks.</time_frame>
    <description>Working memory, inhibitory control, executive function and delay aversion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in activation of front-striatal and parietal brain areas in functional magnetic resonance imaging (fMRI) during a neuropsychological test.</measure>
    <time_frame>Baseline; 12 weeks.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the hours and characteristic of internet use</measure>
    <time_frame>Baseline; 12 weeks</time_frame>
    <description>measured by an appropriate scale (IAT - Internet Addiction Test)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Attention-deficit/Hyperactivity Disorder.</condition>
  <arm_group>
    <arm_group_label>Placebo cognitive training</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>In the control group, we will use a placebo training that will consist of the same exposure time of the active training but not related to any element of cognitive training. To this end, we will set up an online platform with quiz and educational videos - being the most related to school content - without any component of executive function or working memory.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cognitive training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cognitive training with 6 different games each of which gets progressively more difficult as children obtain proficiency.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Cognitive training</intervention_name>
    <description>12 weeks of cognitive training; 4 sessions/week; duration 30 min</description>
    <arm_group_label>Cognitive training</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Placebo cognitive training</intervention_name>
    <description>In the control group, we will use a placebo training that will consist of the same exposure time of the active training but not related to any element of cognitive training. To this end, we will set up an online platform with quiz and educational videos - being the most related to school content - without any component of executive function or working memory.</description>
    <arm_group_label>Placebo cognitive training</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, age 6 to 13 years, ADHD diagnosis (DSM-V)&#xD;
&#xD;
          -  Medicated and stabilized individuals with psychostimulant with residual symptoms of&#xD;
             inattention - mean scores of parents and teachers &gt; or = 1)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of other comorbid mental disorder that is clinically significant and&#xD;
             requiring treatment at the time of entry in the protocol.&#xD;
&#xD;
          -  intelligence quotient (IQ) &lt; 80&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>13 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marcelo Schmitz, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital de Clinicas de Porto Alegre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital de Clínicas de Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande do Sul</state>
        <zip>90035-003</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>April 4, 2014</study_first_submitted>
  <study_first_submitted_qc>July 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <last_update_submitted>December 21, 2015</last_update_submitted>
  <last_update_submitted_qc>December 21, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 22, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ADHD</keyword>
  <keyword>Cognitive training</keyword>
  <keyword>fMRI</keyword>
  <keyword>Cognitive function</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>
  <!-- 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/NCT02184598
org study id: 125002
nct id: NCT02184598
lead sponsor: 
collaborator: 
has dmc: No
Purpose: This project assess the effectiveness of a cognitive training as an add-on
      intervention to drug treatment in children and adolescents diagnosed with
      Attention-Deficit/Hyperactivity Disorder (ADHD) compared to a placebo training. The cognitive
      training consists of 6 computerized games that are based on principles of neuroplastic
      change.

      ADHD: current treatment - International clinical guidelines indicate that pharmacological
      interventions in particular stimulants are the first-line treatment for ADHD. However, about
      30% of children affected by the disorder do not respond to medication alone, exhibit partial
      response or can not tolerate the adverse effects. In addition there is a group of parents who
      do not accept the use of medication for the treatment of ADHD in their children. In recent
      years cognitive training has received considerable attention as a treatment to ADHD. The
      evidence base for cognitive training programs are still forming with few randomized
      placebo-controlled studies. However, this approach seems to be effective either as a
      treatment for ADHD - and others cognitive disorders in childhood - or as a tool to enhance
      cognitive ability and school performance in children and adults. No previous study has
      evaluated this cognitive intervention in a clinical trial with placebo-controlled
      intervention and as an adjunctive treatment to medication. Additionally, the investigators
      will assess brain changes associated with this intervention using neuroimaging (fMRI).
Material and Methods Trial design Randomized clinical trial with placebo control. This study
      will compare the cognitive training program versus the placebo condition to assess the
      reduction on residual symptoms, the improvement in the neurocognitive function and brain
      activation changes in children and adolescents with ADHD receiving stimulants. Sixty
      subjects, six to thirteen years-old with ADHD confirmed by the Kiddie Schedule for Affective
      Disorders and Schizophrenia (K-SADS) will be randomly assigned to 12 weeks of cognitive or
      placebo training.

      Participants To be included in the study children and adolescent need to meet the following
      criteria (a) age between 6-13 years, (b) a diagnosis of ADHD classified according to the
      criteria of the Diagnostic and Statistical Manual of Mental Disorders (5th edition), (c)
      medicated and stabilized with psychostimulants but partially restored - inattention SNAP
      score (mean scores of parents and teachers > or = 1), (d) a full scale intelligence quotient
      (IQ) of at least 80, (e) access to a computer with windows vista 7 and speakers, and access
      to internet. Participants will be excluded in case (a) another comorbid psychiatry diagnosis
      clinically significant and requiring treatment at the time of enter in the study protocol.

      Sample Size Calculation There was no previous study that used the design proposed in this
      investigation. Considering a reduction 20% higher of the SNAP-IV scores in the active group
      intervention (stimulants + cognitive training), sample size in both groups of 27 participants
      and standard-deviation in the magnitude of half of the medium score in each group (moderate
      variability), the study will be able to detect a moderate effect size (ES = 0,4). Calculating
      a sample loss of 10% each group, we define a sample size per group of 30 individuals.

      Cognitive intervention protocol:

      A portuguese version of the new Cognitive Computerized Training was created with the
      partnership of Yale University research team.

      The cognitive training program is composed by computerized exercises with six different games
      divided in multiples levels and sublevels with increasing difficulty. During the games,
      several neuropsychological domains are required from the participant such working memory,
      sustained attention, response inhibition and others. In each session the participant will
      play 6 games divided in 5 minutes blocks. The aim of these games is to engage and activate
      targeted neurocognitive systems This protocol will be run in schools. It will be consisted of
      4 times/week sessions (3 times at school and 1 time at home) for 12 weeks with 30 min of
      duration.

      The placebo cognitive training (control group) will contain the same exposure time of the
      active group but without any element regarding to the cognitive training.

      Pharmacological protocol All subjects must be receiving pharmacological treatment for ADHD
      with a stable dose of stimulants for at least 1 month in doses not inferior of 0.3mg/kg/per
      day of methylphenidate or 30mg/per day of lisdexamphetamine. Any increase in doses during the
      protocol will be permitted.

      Neuropsychological protocol An assessment before the beginning of the intervention and
      pos-treatment will be done by a trained neuropsychologist using three tests of a NIH toolbox
      (C8Kids platform): Flanker Test, Go/NoGo Test and List Sorting Test of Working Memory and a
      neuropsychological battery created by our team using six tests: CPT II (Conner´s Continuous
      Performance Test II), Digit Span, Spatial Span, Reaction Time Task, Trail Making Test and
      Picture Concepts.

      Neuroimaging protocol A subgroup of 10 participants from each group will be drawn to a
      functional resonance exam (MRIf) before and immediately after the cognitive or placebo
      training. During the exam they will do a neuropsychological tests ( Go/NoGo; N-Back - working
      memory - and SAT - sustained attention test).

      Statistical methods Statistical analyses will be performed with Statistical Package for the
      Social Sciences (SPSS) 12.0. The univariate analyses will be performed with the t student
      test / Mann-Whitney to continuous variables or Chi-Square test (X²) / Fischer test to
      categorical variables. The variables that present relationship with the outcomes will be
      maintained in multivariate models. The effective of the intervention over time will be assess
      through analyses of mixed models.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Change in ADHD symptomatology
time frame: Baseline; 12 weeks.
description: Measured by the SNAP scale filled by parents and teachers.
measure: Change in neuropsychological function.
time frame: Baseline; 12 weeks.
description: Working memory, inhibitory control, executive function and delay aversion.
measure: Change in activation of front-striatal and parietal brain areas in functional magnetic resonance imaging (fMRI) during a neuropsychological test.
time frame: Baseline; 12 weeks.
measure: Change in the hours and characteristic of internet use
time frame: Baseline; 12 weeks
description: measured by an appropriate scale (IAT - Internet Addiction Test)
arm group label: Placebo cognitive training
arm group type: Placebo Comparator
description: In the control group, we will use a placebo training that will consist of the same exposure time of the active training but not related to any element of cognitive training. To this end, we will set up an online platform with quiz and educational videos - being the most related to school content - without any component of executive function or working memory.
arm group label: Cognitive training
arm group type: Experimental
description: Cognitive training with 6 different games each of which gets progressively more difficult as children obtain proficiency.
intervention type: Behavioral
intervention name: Cognitive training
description: 12 weeks of cognitive training; 4 sessions/week; duration 30 min
arm group label: Cognitive training
intervention type: Behavioral
intervention name: Placebo cognitive training
description: In the control group, we will use a placebo training that will consist of the same exposure time of the active training but not related to any element of cognitive training. To this end, we will set up an online platform with quiz and educational videos - being the most related to school content - without any component of executive function or working memory.
arm group label: Placebo cognitive training
criteria: 
gender: All
minimum age: 6 Years
maximum age: 13 Years
healthy volunteers: No
last name: Marcelo Schmitz, MD PhD
role: Principal Investigator
affiliation: Hospital de Clinicas de Porto Alegre
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: Hyperkinesis
mesh term: Attention Deficit Disorder with Hyperactivity