Neurally Targeted Cognitive Training to Augment CBT Outcomes in Pediatric Anxiety

Study Overview
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Brief Summary
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This study will assign participants with anxiety to cognitive behavioral therapy (CBT) with computerized cognitive training (CCT). In addition, the study will have a control group and enroll age- and gender-matched anxious children assigned to CBT. The hypothesis of this trial is that CCT with CBT will further increase task control network (TCN) activation and connectivity. Both groups will have one CBT therapy session each week for 12 weeks. However, for participants in the CCT arm plus CBT they will also receive up to 4 weeks of at home CCT to complete during the two weeks prior to the first CBT session and during the two weeks after the first CBT session. CCT is to be done at home for approximately 30 minutes per day, 5 days per week. Additionally, participants in the CCT arm plus CBT will receive CCT for 30 minutes just prior to CBT sessions 4-12. Each group will also have pre and post therapy functional magnetic resonance imaging (fMRI) and be asked to complete anxiety severity interviews and questionnaires throughout the study as well as after the treatment. Update as of 4/7/2020: Enrollment and in-person-only interactions/interventions are temporarily paused due to COVID-19 and are expected to resume in the future. This is not a suspension of IRB approval. Update as of 7/20/2020: Enrollment and in-person-only interactions/interventions are resumed.

Official Title
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Neurally Targeted Cognitive Training to Augment Cognitive Behavioral Therapy (CBT) Outcomes in Pediatric Anxiety

Conditions
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Anxiety Disorders

Intervention / Treatment
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* Behavioral: Cognitive behavioral therapy (CBT)
* Behavioral: computerized cognitive training (CCT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parent or guardian willing to give informed consent, and children willing to give informed assent to participate in the study Must be actively enrolled and maintain eligibility in Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety (HUM00118950; P.I. Fitzgerald) to participate in the study. Exclusion Criteria: Color blindness

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBT and computerized cognitive training (CCT)<br>Participants will play CCT games at home 5 times per week for two weeks before beginning CBT and for two weeks after the first CBT session. Then participants will have CCT games immediately prior to CBT for nine more weeks (one time a week). | Behavioral: Cognitive behavioral therapy (CBT)<br>* The CBT intervention will consist of 12 weekly 60 minute sessions of the manualized therapy, adapted from the Coping Cat program, for the treatment of pediatric anxiety disorders.<br>Behavioral: computerized cognitive training (CCT)<br>* CCT intervention will consist of approximately 30 minutes of CCT games prior to each CBT session, to engage cognitive control capacity prior to receipt of CBT. The CCT games will be designed to target focused attention, response inhibition, working memory and multiple simultaneous attention to constitute a general executive function training, and activate neural systems associated with executive function/cognitive control. Difficulty of the games will be titrated individually and by session to avoid boredom and progressively activate the functional systems underlying cognitive control.<br>|
| Active Comparator: Cognitive behavioral therapy<br>Participants will receive CBT sessions once a week for 12 weeks. | Behavioral: Cognitive behavioral therapy (CBT)<br>* The CBT intervention will consist of 12 weekly 60 minute sessions of the manualized therapy, adapted from the Coping Cat program, for the treatment of pediatric anxiety disorders.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Brain Activation and Connectivity in the Task-control Network (TCN) | Pre- to post-CBT changes in brain activation and function connectivity in the task-control network including fronto-parietal and cingulo-opercular regions mediating cognitive control. Functional activation and connectivity of these brain regions are assessed using a conflict interference computer task performed during MRI scanning. | Baseline, 12 weeks (after therapy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pediatric Anxiety Rating Score (PARS) | This is a 50-question interview-based tool used to assess for the presence and severity of anxiety symptoms in children and adolescents utilizing parental and youth input to guide clinician ratings. The total scores on this scale range from 0 to 30, with scores above 13 indicating clinically meaningful anxiety. The numbers presented represent the value at 12 weeks minus the value at baseline | Baseline, 12 weeks (after therapy) | 
| Change in Behavioral Performance on the Conflict Interference Task- Conflict Task Reaction Times | Pre- to post-CBT changes in the behavioral performance in a conflict interference task. The time for the task at 12 weeks minus at baseline yields a number whose absolute value of change is shown below. Thus, when assessing the change, the higher number corresponds to more improvement in reaction time. | Baseline, 12 weeks (after therapy) | 
| Change in Behavioral Performance on the Conflict Interference Task- Conflict Task Accuracy | Pre- to post-CBT changes in the behavioral performance in a conflict interference task. Conflict interference task refers to a task assigned to a participant to complete that also includes some form of distraction or condition that interferes with completion of the task. For this, the lower number indicates more improvement in accuracy in competing the task. | Baseline, 12 weeks (after therapy) | 
| Change in Tasks Testing Cognitive Control Capacity Included in the NIH Toolbox | Pre- to post-CBT changes in the NIH toolbox composite score from the cognitive control module included in the toolbox. The NIH toolbox standard score has a mean of 100 and standard deviation (SD) of 15. The lower the change in the score between the pre- and the post-CBT changes indicates the higher degree of improvement. | Baseline, 12 weeks (after therapy) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anxious, Cognitive behavioral therapy, Computerized cognitive training