<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/NCT03023644</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-P00022440</org_study_id>
    <nct_id>NCT03023644</nct_id>
  </id_info>
  <brief_title>Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study</brief_title>
  <official_title>Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>United States Department of Defense</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Boston Children's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Each year, approximately 1 child in every 100 is born with Congenital Heart Disease (CHD),&#xD;
      making it the most common birth defect. With recent medical advances, more children with CHD&#xD;
      survive early open-heart surgery, so that there are now 2 to 3 million adult survivors with&#xD;
      CHD. These survivors face challenges in terms of their cognitive and behavioral development.&#xD;
      For many, the limitations affect their academic achievement, social adaption and, ultimately,&#xD;
      their quality of life. Among the most disabling limitations are those that pertain to the&#xD;
      ability to maintain attention, plan and organize activities, regulate emotions, and develop&#xD;
      problem-solving strategies. Collectively, these are referred to as executive functions (EF)&#xD;
      because they are higher-order abilities that enable one to coordinate complex behaviors.&#xD;
      Additionally, impaired EF also underlie mental health disorders. In spite of the abundance of&#xD;
      evidence that children with CHD struggle with EF, there is little to offer them in the way of&#xD;
      evidence-based interventions to prevent or mitigate these problems.&#xD;
&#xD;
      The investigators propose to conduct the first randomized trial to evaluate the efficacy of&#xD;
      an intervention, the Cogmed Working Memory Program, in improving the neurodevelopment&#xD;
      outcomes of children with critical CHD after infant open-heart surgery. Children who meet&#xD;
      eligibility criteria and who agree to participate will be randomly assigned to an&#xD;
      intervention or control group. Children in the intervention group will complete 25 35-40&#xD;
      minute sessions of Cogmed training, spread over for 5 weeks. This Program is a set of&#xD;
      home-based, child-friendly, computerized activities. The control group will receive the&#xD;
      standard of care for children with CHD. Children's scores on EF and related&#xD;
      neurodevelopmental tests will be evaluated before the intervention group completes Cogmed&#xD;
      training, at the conclusion of their training, and 3 months later. The latter assessment will&#xD;
      indicate whether any gains in EF skills of the children in the intervention group are&#xD;
      sustained after training. Parents and teachers will also complete questionnaires about&#xD;
      children's EF, attention, and social behaviors to determine whether training affects&#xD;
      behaviors of the intervention group at home and in school. The investigators will also&#xD;
      identify the medical and surgical characteristics of children who benefit most from Cogmed&#xD;
      training. This information will be helpful in targeting the intervention most efficiently in&#xD;
      the future.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 21, 2017</start_date>
  <completion_date type="Actual">September 30, 2020</completion_date>
  <primary_completion_date type="Actual">December 1, 2019</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>Other</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline scores at the computerized Working Memory Test from the NIH Toolbox Assessment of Neurological and Behavioral Function at post-treatment assessment</measure>
    <time_frame>2 weeks</time_frame>
    <description>This standardized measure assesses the ability to process information across a series of modalities (visual-spatial and verbal), to hold this information in a short-term buffer, and to actively manipulate it mentally. It is considered an excellent composite indicator of children's executive function skills, as it requires the simultaneous implementation of control of attention and working memory abilities on tasks of increasing complexity. Mean scores are automatically computed and are compared to a standardization sample of US children of the same age. They are normally distributed (mean=100, SD=15).</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">106</enrollment>
  <condition>Congenital Heart Defect</condition>
  <condition>Executive Function</condition>
  <condition>Children</condition>
  <condition>Neurodevelopmental Disorders</condition>
  <condition>Working Memory</condition>
  <condition>Infant Open Heart Surgery</condition>
  <arm_group>
    <arm_group_label>Cogmed Working Memory Training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The group randomized to the intervention will receive Cogmed computerized training of executive function and attention skills. The standard Cogmed RM will be used for this trial arm. This is a child-friendly web-based software program. The investigators will use a version of the program that contains 12 different neurocognitive tasks. Tasks become more difficult as a function of performance on a session-by-session basis. Each training session lasts 35-40 minutes, with one session to be completed per day 5 days each week for 5 weeks, for a total of 25 sessions. The program yields individual session-by-session and task-by- task training results, including the children's responses, time spent on each task, and evolution curves.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Children randomly assigned to the control group will receive the standard of care recommended for patients with critical CHD. This includes cardiac surveillance and neurodevelopmental counseling and screening at our Cardiac Neurodevelopmental Program if needed. Once enrolled in our study, a child in the control group will not receive Cogmed intervention or any other cognitive intervention that targets executive functions or ADHD symptoms until after the 3-month follow-up neurodevelopmental evaluation is performed, i.e., 5-6 months after initial enrollment. Like children assigned to the intervention group, controls can continue on treatments that are already in place for other neurodevelopmental disabilities (e.g., speech therapy, occupational services).</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Cogmed Working Memory Training</intervention_name>
    <description>Cogmed Working Memory Program will be used as a computerized home-based intervention. Families will an iPad with a web-based software program. The 25 sessions will be completed individually by the child with parental supervision. For the first 5 sessions, the participant trains on the same set of games; on the 6th session and every 5th session thereafter, a new task is introduced and replaces one of the initial tasks. At the end of each session, the child can play an age-appropriate computerized game as a reward. After each session, results are uploaded by parents to a secure website, to keep track of the participant's progress. Families will be contacted weekly to check program function and discuss concerns.</description>
    <arm_group_label>Cogmed Working Memory Training</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Open heart surgery before age 12 months of life&#xD;
&#xD;
          2. Ages between 7 years 0 months and 12 years 11 months&#xD;
&#xD;
          3. ≥6 months post-cardiac surgery at enrollment&#xD;
&#xD;
          4. Cardiology follow-up (clinic or inpatient) at BCH or other affiliated center in the&#xD;
             last 6 years.&#xD;
&#xD;
          5. English and/or Spanish speaking&#xD;
&#xD;
          6. Informed consent of parent/guardian as well as assent of child&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known chromosomal anomalies and/or genetic syndromes&#xD;
&#xD;
          2. Severe physical and/or sensory impairments (hearing, visual, or psychomotor) that&#xD;
             would prevent use of the computerized program and tablets&#xD;
&#xD;
          3. Confirmed formal diagnosis of any autism spectrum disorder or a severe developmental&#xD;
             and/or intellectual disorder that would prevent successful completion of the planned&#xD;
             study testing.&#xD;
&#xD;
          4. Scheduled to undergo major cardiac interventions in the 6 months following enrollment&#xD;
&#xD;
          5. Received, receiving, or scheduled to receive Cogmed or any other computerized&#xD;
             behavioral training program targeting executive functions or ADHD&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jane W Newburger, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Boston Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>January 13, 2017</study_first_submitted>
  <study_first_submitted_qc>January 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>January 28, 2021</last_update_submitted>
  <last_update_submitted_qc>January 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Boston Children's Hospital</investigator_affiliation>
    <investigator_full_name>Jane W. Newburger</investigator_full_name>
    <investigator_title>MD, MPH, Commonwealth Professor of Pediatrics</investigator_title>
  </responsible_party>
  <keyword>Congenital Heart Disease</keyword>
  <keyword>Neurodevelopmental Disorders</keyword>
  <keyword>Children</keyword>
  <keyword>Executive Function</keyword>
  <keyword>Working Memory</keyword>
  <keyword>Cognitive interventions</keyword>
  <keyword>Infant Open Heart Surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Heart Defects, Congenital</mesh_term>
    <mesh_term>Neurodevelopmental Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>We will share the final research data, including the computerized dataset upon which publications were based. The final dataset may also include both raw data and derived variables. Data products from this study will be made available without cost to researchers and analysts. User registration will be required in order to access or download files. As part of the registration process, users must agree to the conditions of use governing access to the public release data, including restrictions against attempting to identify study participants, destruction of the data after analyses are completed, reporting responsibilities, restrictions on redistribution of the data to third parties, and proper acknowledgement of the data resource. We are aware of the need to protect human subject information and Protected Health Information in accordance with HIPPA standards and in other situations where data sharing may not be appropriate or allowed. Data sharing will occur in a timely fashion.</ipd_description>
  </patient_data>
  <!-- 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/NCT03023644
org study id: IRB-P00022440
nct id: NCT03023644
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Each year, approximately 1 child in every 100 is born with Congenital Heart Disease (CHD),
      making it the most common birth defect. With recent medical advances, more children with CHD
      survive early open-heart surgery, so that there are now 2 to 3 million adult survivors with
      CHD. These survivors face challenges in terms of their cognitive and behavioral development.
      For many, the limitations affect their academic achievement, social adaption and, ultimately,
      their quality of life. Among the most disabling limitations are those that pertain to the
      ability to maintain attention, plan and organize activities, regulate emotions, and develop
      problem-solving strategies. Collectively, these are referred to as executive functions (EF)
      because they are higher-order abilities that enable one to coordinate complex behaviors.
      Additionally, impaired EF also underlie mental health disorders. In spite of the abundance of
      evidence that children with CHD struggle with EF, there is little to offer them in the way of
      evidence-based interventions to prevent or mitigate these problems.

      The investigators propose to conduct the first randomized trial to evaluate the efficacy of
      an intervention, the Cogmed Working Memory Program, in improving the neurodevelopment
      outcomes of children with critical CHD after infant open-heart surgery. Children who meet
      eligibility criteria and who agree to participate will be randomly assigned to an
      intervention or control group. Children in the intervention group will complete 25 35-40
      minute sessions of Cogmed training, spread over for 5 weeks. This Program is a set of
      home-based, child-friendly, computerized activities. The control group will receive the
      standard of care for children with CHD. Children's scores on EF and related
      neurodevelopmental tests will be evaluated before the intervention group completes Cogmed
      training, at the conclusion of their training, and 3 months later. The latter assessment will
      indicate whether any gains in EF skills of the children in the intervention group are
      sustained after training. Parents and teachers will also complete questionnaires about
      children's EF, attention, and social behaviors to determine whether training affects
      behaviors of the intervention group at home and in school. The investigators will also
      identify the medical and surgical characteristics of children who benefit most from Cogmed
      training. This information will be helpful in targeting the intervention most efficiently in
      the future.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Single (Outcomes Assessor)
measure: Change from baseline scores at the computerized Working Memory Test from the NIH Toolbox Assessment of Neurological and Behavioral Function at post-treatment assessment
time frame: 2 weeks
description: This standardized measure assesses the ability to process information across a series of modalities (visual-spatial and verbal), to hold this information in a short-term buffer, and to actively manipulate it mentally. It is considered an excellent composite indicator of children's executive function skills, as it requires the simultaneous implementation of control of attention and working memory abilities on tasks of increasing complexity. Mean scores are automatically computed and are compared to a standardization sample of US children of the same age. They are normally distributed (mean=100, SD=15).
arm group label: Cogmed Working Memory Training
arm group type: Experimental
description: The group randomized to the intervention will receive Cogmed computerized training of executive function and attention skills. The standard Cogmed RM will be used for this trial arm. This is a child-friendly web-based software program. The investigators will use a version of the program that contains 12 different neurocognitive tasks. Tasks become more difficult as a function of performance on a session-by-session basis. Each training session lasts 35-40 minutes, with one session to be completed per day 5 days each week for 5 weeks, for a total of 25 sessions. The program yields individual session-by-session and task-by- task training results, including the children's responses, time spent on each task, and evolution curves.
arm group label: Standard of Care
arm group type: No Intervention
description: Children randomly assigned to the control group will receive the standard of care recommended for patients with critical CHD. This includes cardiac surveillance and neurodevelopmental counseling and screening at our Cardiac Neurodevelopmental Program if needed. Once enrolled in our study, a child in the control group will not receive Cogmed intervention or any other cognitive intervention that targets executive functions or ADHD symptoms until after the 3-month follow-up neurodevelopmental evaluation is performed, i.e., 5-6 months after initial enrollment. Like children assigned to the intervention group, controls can continue on treatments that are already in place for other neurodevelopmental disabilities (e.g., speech therapy, occupational services).
intervention type: Behavioral
intervention name: Cogmed Working Memory Training
description: Cogmed Working Memory Program will be used as a computerized home-based intervention. Families will an iPad with a web-based software program. The 25 sessions will be completed individually by the child with parental supervision. For the first 5 sessions, the participant trains on the same set of games; on the 6th session and every 5th session thereafter, a new task is introduced and replaces one of the initial tasks. At the end of each session, the child can play an age-appropriate computerized game as a reward. After each session, results are uploaded by parents to a secure website, to keep track of the participant's progress. Families will be contacted weekly to check program function and discuss concerns.
arm group label: Cogmed Working Memory Training
criteria: 
gender: All
minimum age: 7 Years
maximum age: 12 Years
healthy volunteers: No
last name: Jane W Newburger, MD, MPH
role: Principal Investigator
affiliation: Boston Children's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Boston Children's Hospital
investigator full name: Jane W. Newburger
investigator title: MD, MPH, Commonwealth Professor of Pediatrics
mesh term: Heart Diseases
mesh term: Heart Defects, Congenital
mesh term: Neurodevelopmental Disorders
sharing ipd: Yes
ipd description: We will share the final research data, including the computerized dataset upon which publications were based. The final dataset may also include both raw data and derived variables. Data products from this study will be made available without cost to researchers and analysts. User registration will be required in order to access or download files. As part of the registration process, users must agree to the conditions of use governing access to the public release data, including restrictions against attempting to identify study participants, destruction of the data after analyses are completed, reporting responsibilities, restrictions on redistribution of the data to third parties, and proper acknowledgement of the data resource. We are aware of the need to protect human subject information and Protected Health Information in accordance with HIPPA standards and in other situations where data sharing may not be appropriate or allowed. Data sharing will occur in a timely fashion.