Anxiety Disorders
Conditions
Keywords
anxious, Cognitive behavioral therapy, Computerized cognitive training
Brief summary
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.
Interventions
BEHAVIORALCognitive behavioral therapy (CBT)
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.
BEHAVIORALcomputerized cognitive training (CCT)
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.
Sponsors
National Institutes of Health (NIH)
University of Michigan
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Caregiver)
Masking description
A clinician, blind to whether patients are completing CCT or not, will deliver CBT to the patients.
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brain Activation and Connectivity in the Task-control Network (TCN) | Baseline, 12 weeks (after therapy) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pediatric Anxiety Rating Score (PARS) | Baseline, 12 weeks (after therapy) | 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 |
| Change in Behavioral Performance on the Conflict Interference Task- Conflict Task Reaction Times | Baseline, 12 weeks (after therapy) | 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. |
| Change in Behavioral Performance on the Conflict Interference Task- Conflict Task Accuracy | Baseline, 12 weeks (after therapy) | 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. |
| Change in Tasks Testing Cognitive Control Capacity Included in the NIH Toolbox | Baseline, 12 weeks (after therapy) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cognitive Behavioral Therapy (CBT) and Computerized Cognitive Training (CCT) 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).
Cognitive behavioral therapy (CBT): 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.
computerized cognitive training (CCT): 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. | 6 |
| Cognitive Behavioral Therapy (CBT) Participants will receive CBT sessions once a week for 12 weeks.
Cognitive behavioral therapy (CBT): 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. | 12 |
| Participants Who Did Not Complete Participants who were assigned to the Cognitive behavioral therapy arm, but who withdrew or did not complete the trial. Data from the participants in this arm was not included in the outcome measure data. | 3 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not obtain second fMRI. | 0 | 1 |
| Overall Study | MRI failed/no second fMRI | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Cognitive Behavioral Therapy (CBT) and Computerized Cognitive Training (CCT) | Cognitive Behavioral Therapy (CBT) | Participants Who Did Not Complete | Total |
|---|---|---|---|---|
| Age, Continuous | 14.3 years STANDARD_DEVIATION 3.6 | 12.4 years STANDARD_DEVIATION 2.7 | 10.2 years STANDARD_DEVIATION 1 | 12.6 years STANDARD_DEVIATION 3 |
| Brain Activation and Connectivity in the Task-control Network (TCN) leftdACC | 0.876 Arbitrary Units STANDARD_DEVIATION 0.31 | 0.681 Arbitrary Units STANDARD_DEVIATION 0.418 | 0.607 Arbitrary Units STANDARD_DEVIATION 0.664 | 0.705 Arbitrary Units STANDARD_DEVIATION 0.41 |
| Brain Activation and Connectivity in the Task-control Network (TCN) leftIFG | 0.66 Arbitrary Units STANDARD_DEVIATION 0.18 | 0.696 Arbitrary Units STANDARD_DEVIATION 0.421 | 0.169 Arbitrary Units STANDARD_DEVIATION 0.258 | 0.612 Arbitrary Units STANDARD_DEVIATION 0.369 |
| Brain Activation and Connectivity in the Task-control Network (TCN) leftInsula | 0.535 Arbitrary Units STANDARD_DEVIATION 0.099 | 0.438 Arbitrary Units STANDARD_DEVIATION 0.379 | 0.086 Arbitrary Units STANDARD_DEVIATION 0.345 | 0.416 Arbitrary Units STANDARD_DEVIATION 0.325 |
| Brain Activation and Connectivity in the Task-control Network (TCN) leftParietal | -0.002 Arbitrary Units STANDARD_DEVIATION 0.586 | 0.066 Arbitrary Units STANDARD_DEVIATION 0.576 | 0.659 Arbitrary Units STANDARD_DEVIATION 0.064 | 0.058 Arbitrary Units STANDARD_DEVIATION 0.591 |
| Brain Activation and Connectivity in the Task-control Network (TCN) rightdACC | 0.997 Arbitrary Units STANDARD_DEVIATION 0.489 | 1.026 Arbitrary Units STANDARD_DEVIATION 0.719 | 0.678 Arbitrary Units STANDARD_DEVIATION 0.72 | 0.971 Arbitrary Units STANDARD_DEVIATION 0.612 |
| Brain Activation and Connectivity in the Task-control Network (TCN) rightIFG | 0.739 Arbitrary Units STANDARD_DEVIATION 0.423 | 0.801 Arbitrary Units STANDARD_DEVIATION 0.798 | 0.428 Arbitrary Units STANDARD_DEVIATION 1.209 | 0.720 Arbitrary Units STANDARD_DEVIATION 0.694 |
| Brain Activation and Connectivity in the Task-control Network (TCN) rightInsula | 0.73 Arbitrary Units STANDARD_DEVIATION 0.289 | 0.573 Arbitrary Units STANDARD_DEVIATION 0.41 | 0.433 Arbitrary Units STANDARD_DEVIATION 1.141 | 0.571 Arbitrary Units STANDARD_DEVIATION 0.463 |
| Brain Activation and Connectivity in the Task-control Network (TCN) rightParietal | 1.037 Arbitrary Units STANDARD_DEVIATION 0.356 | 0.679 Arbitrary Units STANDARD_DEVIATION 0.605 | 1.038 Arbitrary Units STANDARD_DEVIATION 1.296 | 0.791 Arbitrary Units STANDARD_DEVIATION 0.614 |
| Brain Activation and Connectivity in the Task-control Network (TCN) TCN | 0.20 Arbitrary Units STANDARD_DEVIATION 0.51 | 0.50 Arbitrary Units STANDARD_DEVIATION 0.24 | NA Arbitrary Units | 0.50 Arbitrary Units STANDARD_DEVIATION 0.23 |
| Conflict Task Accuracy | 91 Percentage of correct responses STANDARD_DEVIATION 3 | 86 Percentage of correct responses STANDARD_DEVIATION 7 | 92.2 Percentage of correct responses STANDARD_DEVIATION 1 | 88.3 Percentage of correct responses STANDARD_DEVIATION 6 |
| Conflict Task Reaction Times | 800.8 milliseconds STANDARD_DEVIATION 365.5 | 885.9 milliseconds STANDARD_DEVIATION 256.7 | 1164.2 milliseconds STANDARD_DEVIATION 421.2 | 888.2 milliseconds STANDARD_DEVIATION 305 |
| NIH Toolbox Composite Score | 111.2 T-score STANDARD_DEVIATION 4.8 | 101.9 T-score STANDARD_DEVIATION 11.4 | 106 T-score | 105.0 T-score STANDARD_DEVIATION 10.2 |
| Pediatric Anxiety Rating Score (PARS) | 12.5 Score on a Scale STANDARD_DEVIATION 3.3 | 19.2 Score on a Scale STANDARD_DEVIATION 2.6 | 17.7 Score on a Scale STANDARD_DEVIATION 3.1 | 17.4 Score on a Scale STANDARD_DEVIATION 3.8 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiracial: black/white/native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiracial: Bosniak | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiracial: Caucasian/Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other: Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 9 Participants | 3 Participants | 16 Participants |
| Region of Enrollment United States | 6 participants | 12 participants | 3 participants | 21 participants |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 2 Participants | 16 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 15 |
| other Total, other adverse events | 0 / 6 | 0 / 15 |
| serious Total, serious adverse events | 0 / 6 | 0 / 15 |
Outcome results
Primary
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.
Time frame: Baseline, 12 weeks (after therapy)
Population: One participant's fMRI data in the Cognitive Behavioral Therapy arm was not usable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CBT and Computerized Cognitive Training (CCT) | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | leftIFG (Change in Brain activity [post minus pre]) | 0.020 Arbitrary Units | Standard Deviation 0.151 |
| CBT and Computerized Cognitive Training (CCT) | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | rightParietal (Change in Brain activity [post minus pre]) | -0.356 Arbitrary Units | Standard Deviation 0.375 |
| CBT and Computerized Cognitive Training (CCT) | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | TCN (Change in Connectivity [post minus pre]) | 0.20 Arbitrary Units | Standard Deviation 0.47 |
| CBT and Computerized Cognitive Training (CCT) | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | leftdACC (Change in Brain activity [post minus pre]) | -0.246 Arbitrary Units | Standard Deviation 0.26 |
| CBT and Computerized Cognitive Training (CCT) | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | rightIFG (Change in Brain activity [post minus pre]) | 0.305 Arbitrary Units | Standard Deviation 0.742 |
| CBT and Computerized Cognitive Training (CCT) | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | rightdACC (Change in Brain activity [post minus pre]) | -0.203 Arbitrary Units | Standard Deviation 0.909 |
| CBT and Computerized Cognitive Training (CCT) | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | leftParietal (Change in Brain activity [post minus pre]) | 0.082 Arbitrary Units | Standard Deviation 0.095 |
| CBT and Computerized Cognitive Training (CCT) | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | leftInsula (Change in Brain activity [post minus pre]) | -0.221 Arbitrary Units | Standard Deviation 0.399 |
| CBT and Computerized Cognitive Training (CCT) | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | rightInsula (Change in Brain activity [post minus pre]) | -0.166 Arbitrary Units | Standard Deviation 0.541 |
| Cognitive Behavioral Therapy | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | leftInsula (Change in Brain activity [post minus pre]) | 0.081 Arbitrary Units | Standard Deviation 0.388 |
| Cognitive Behavioral Therapy | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | rightInsula (Change in Brain activity [post minus pre]) | 0.067 Arbitrary Units | Standard Deviation 0.702 |
| Cognitive Behavioral Therapy | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | TCN (Change in Connectivity [post minus pre]) | 0.53 Arbitrary Units | Standard Deviation 0.26 |
| Cognitive Behavioral Therapy | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | leftIFG (Change in Brain activity [post minus pre]) | -0.206 Arbitrary Units | Standard Deviation 0.561 |
| Cognitive Behavioral Therapy | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | rightIFG (Change in Brain activity [post minus pre]) | -0.004 Arbitrary Units | Standard Deviation 0.653 |
| Cognitive Behavioral Therapy | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | leftParietal (Change in Brain activity [post minus pre]) | -0.096 Arbitrary Units | Standard Deviation 0.559 |
| Cognitive Behavioral Therapy | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | rightParietal (Change in Brain activity [post minus pre]) | -0.032 Arbitrary Units | Standard Deviation 0.66 |
| Cognitive Behavioral Therapy | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | leftdACC (Change in Brain activity [post minus pre]) | 0.164 Arbitrary Units | Standard Deviation 0.405 |
| Cognitive Behavioral Therapy | Change in Brain Activation and Connectivity in the Task-control Network (TCN) | rightdACC (Change in Brain activity [post minus pre]) | -0.270 Arbitrary Units | Standard Deviation 1.069 |
Comparison: leftIFG (Change in Brain activity \[post minus pre\])
Comparison: rightIFG (Change in Brain activity \[post minus pre\])
Comparison: leftParietal (Change in Brain activity \[post minus pre\])
Comparison: rightParietal (Change in Brain activity \[post minus pre\])
Comparison: leftdACC (Change in Brain activity \[post minus pre\])
Comparison: rightdACC (Change in Brain activity \[post minus pre\])
Comparison: leftInsula (Change in Brain activity \[post minus pre\])
Comparison: rightInsula (Change in Brain activity \[post minus pre\])
Comparison: TCN (Change in Connectivity \[post minus pre\])
Secondary
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.
Time frame: Baseline, 12 weeks (after therapy)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBT and Computerized Cognitive Training (CCT) | Change in Behavioral Performance on the Conflict Interference Task- Conflict Task Accuracy | -4.6 percentage of correct responses | Standard Deviation 3.6 |
| Cognitive Behavioral Therapy | Change in Behavioral Performance on the Conflict Interference Task- Conflict Task Accuracy | 9 percentage of correct responses | Standard Deviation 6.8 |
p-value: 0.042t-test, 1 sided
Secondary
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.
Time frame: Baseline, 12 weeks (after therapy)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBT and Computerized Cognitive Training (CCT) | Change in Behavioral Performance on the Conflict Interference Task- Conflict Task Reaction Times | 27.4 milliseconds | Standard Deviation 55.3 |
| Cognitive Behavioral Therapy | Change in Behavioral Performance on the Conflict Interference Task- Conflict Task Reaction Times | 70.7 milliseconds | Standard Deviation 135 |
p-value: 0.233t-test, 1 sided
Secondary
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
Time frame: Baseline, 12 weeks (after therapy)
Population: Data for 2 participants in the CBT and computerized cognitive training (CCT) arm are missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBT and Computerized Cognitive Training (CCT) | Change in Pediatric Anxiety Rating Score (PARS) | -5 score on a scale | Standard Deviation 6.8 |
| Cognitive Behavioral Therapy | Change in Pediatric Anxiety Rating Score (PARS) | -7.1 score on a scale | Standard Deviation 4.4 |
p-value: 0.241t-test, 1 sided
Secondary
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.
Time frame: Baseline, 12 weeks (after therapy)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBT and Computerized Cognitive Training (CCT) | Change in Tasks Testing Cognitive Control Capacity Included in the NIH Toolbox | -6.6 T-score | Standard Deviation 10.7 |
| Cognitive Behavioral Therapy | Change in Tasks Testing Cognitive Control Capacity Included in the NIH Toolbox | -8.4 T-score | Standard Deviation 7.8 |
p-value: 0.349t-test, 1 sided