Asperger's Syndrome, Autism, Autism Spectrum Disorders, Generalized Anxiety Disorder, Obsessive-compulsive Disorder, Pervasive Developmental Disability - Not Otherwise Specified, Separation Anxiety Disorder, Social Phobia, Specific Phobia
Conditions
Keywords
Autism spectrum disorders, Autism, Asperger's syndrome, Pervasive developmental disability - not otherwise specified, obsessive-compulsive disorder, Social phobia, Generalized anxiety disorder, Specific phobia, Separation anxiety disorder, Counseling, Cognitive-behavioral therapy, Psychotherapy
Brief summary
Anxiety disorders affect 40 to 50% of children with autism spectrum disorders (ASD), contributing to substantial distress and impairment. The goal of this study is to examine the effectiveness of a personalized type of psychotherapy against standard-care psychotherapy for addressing anxiety in youth with ASD.
Detailed description
Autism spectrum disorders (ASD) are common neurodevelopmental syndromes affecting 1% of U.S. children. Comorbid anxiety disorders affect 40 to 50% of children with ASD, causing substantial distress and impairment over and above that caused by ASD alone. Although standard practice cognitive-behavioral therapy (CBT) has been established as an efficacious and safe treatment for anxiety disorders among typically developing youth, its utility in comorbid cases with ASD remains unknown. To date, no studies have experimentally compared standard practice CBT to a cognitive-behavioral intervention that has been personalized for children with a comorbid presentation of anxiety and ASD. Accordingly, we are proposing a randomized controlled trial to be conducted at three treatment sites to evaluate the efficacy of personalized CBT for anxiety in ASD (Behavioral Intervention for Anxiety in Children with Autism: BIACA) relative to standard practice CBT for anxiety (Coping Cat program). Furthermore, this study will employ a waitlist control group to assess the efficacy of each CBT arm relative to the absence of treatment (i.e., a Waitlist control arm). The proposed research will: (1) examine the efficacy of BIACA relative to Coping Cat, which represents standard practice treatment, and the efficacy of both these treatments relative to a waitlist control group, (2) evaluate the maintenance of treatment gains, (3) examine the impact of personalized intervention on functional outcomes. A total of 201youth across 3 study locations (ages 8-13 years) with ASD and co-occurring anxiety will be randomly assigned to one of the three conditions. The three recruitment sites for this study are University of California, Los Angeles, the University of South Florida (USF), and Temple University. Considering the rising number of children diagnosed with ASD together with the frequency and severity of comorbid anxiety, the proposed work is tailored to the unique needs of youth with ASD and will provide a timely contribution to public health efforts.
Interventions
BEHAVIORALPersonalized Cognitive-behavioral therapy
BEHAVIORALStandard Practice Cognitive-behavioral therapy
BEHAVIORALTreatment as Usual
Sponsors
Temple University
University of California, Los Angeles
University of South Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
7 Years to 13 Years
Healthy volunteers
Yes
Inclusion criteria
* Outpatient boys and girls with ASD between the ages 7-13 years at consent/assent. * The child meets criteria for ASD. * The child meets criteria for clinically significant anxiety symptoms. * The child has a Full Scale and Verbal Comprehension Intelligence Quotient \>70 as assessed on the Wechsler Intelligence Scale for Children-IV or another acceptable Intelligence Quotient test.
Exclusion criteria
* Receiving concurrent therapy targeting anxiety, social skills training with homework, or behavioral interventions (e.g., applied behavior analysis). This excludes academic tutoring, occupational therapy, speech therapy, school counseling that is no more than 60 minutes per week in duration, school aides, and social skills training groups that do not include homework and are no more than 60 minutes/week in duration. * (a) Current clinically significant suicidality or (b) individuals who have engaged in suicidal behaviors within 6 months will be excluded and referred for appropriate clinical intervention. * Child has been nonresponsive to an adequate trial of CBT for anxiety within the previous 2 years. * Lifetime bipolar disorder, schizophrenia or schizoaffective disorder. * Initiation of an antidepressant medication within 12 weeks before study enrollment or an antipsychotic medication 6 weeks before study enrollment or the child has changed the dose of an established medication within 8 weeks before study enrollment (4 weeks for antipsychotic) or during psychotherapy (unless the dose is lowered because of side effects).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Anxiety Severity on the Pediatric Anxiety Rating Scale After 16 Weeks of Treatment. | Baseline and After 16 Weeks of Treatment | This measure is administered by a clinician and assesses anxiety symptom severity on a scale from 0-25 with higher scores corresponding to worse anxiety. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Positive Treatment Response as Assessed by the Clinical Global Impressions-Improvement Scale | After 16 weeks of treatment | The Clinical Global Impressions-Improvement scale (CGI-I) was completed by a clinician after 16 weeks of treatment. The CGI-I assesses the severity of anxiety on a 7 point scale, ranging from 1 (very much improved) to 7 (very much worse). A rating of 1 or 2 on the CGI-I designated a positive treatment response. |
| Change From Baseline in Anxiety/Depression Severity on the Child Behavior Checklist After 16 Weeks of Treatment. | Baseline and After 16 weeks of treatment | The Child Behavior Checklist (CBCL) is completed by parents and the anxiety/depression subscale of the CBCL was used to assess anxiety/depression symptomatology. The CBCL anxiety/depression subscale is rated on a 3-point scale, ranging from 0 (Not true) to 2 (Very True), with higher scores indicating more symptoms. |
| Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Baseline and After 16 weeks of treatment | The Childhood Anxiety Impact Scale (CAIS) is a questionnaire completed by parents about the impact of the child's anxiety on functioning in three situational categories (i.e., school, social, and family functioning). The CAIS is rated on a 4-point scale, ranging from 0 (not at all) to 3 (very much). The CAIS items are summed and sorted into 3 subscales, corresponding to each situational category: school, social, and family. For all 3 subscales, higher scores correspond to more associated impact in that area. |
Countries
United States
Participant flow
Recruitment details
Two-hundred and fourteen children between 7-13 years (M=9.96, SD=1.76) were recruited through referrals, advertisements, and the patient flow of three university-based mental health clinics. Recruitment began April 2014 and final data were collected around January 2017.
Pre-assignment details
Of the 214 participants enrolled in the study, a total of 47 children were excluded before assignment to groups because they did not meet eligibility criteria (did not meet IQ criteria (n=6); did not meet anxiety criteria or anxiety was not primary (n=16); no autism spectrum disorder criteria (n=17); parent unwilling or unable to adhere to study procedures (n=7); child needed a higher level of care (n=1)). Thus, only 167 children were assigned across the three groups.
Participants by arm
| Arm | Count |
|---|---|
| Personalized Cognitive-behavioral Therapy Personalized Cognitive-behavioral therapy involves 16 weekly individual therapy sessions, up to 90 minutes each, based on a treatment protocol that has been designed specifically for youth with high-functioning autism spectrum disorders.
Personalized Cognitive-behavioral therapy | 77 |
| Standard Practice Cognitive-behavioral Therapy Standard Practice Cognitive-behavioral therapy involves 16 weekly individual therapy sessions, up to 60 minutes each, based on a treatment protocol that represent the standard practice psychotherapy for anxiety that has been found to be effective in multiple trials in youngsters without autism spectrum disorders.
Standard Practice Cognitive-behavioral therapy | 71 |
| Treatment as Usual Participants randomized to the TAU condition will be instructed to continue receiving their prior interventions as recommended by their providers (e.g., psychotherapy, social skills training, behavioral interventions, family participation in family therapy or a parenting class, or pharmacological interventions) for a 16-week period. Treatment changes (e.g., medication increase, starting psychotherapy in community) are not prohibited and will be monitored. Thus, treatment will continue as it would in standard practice; and will be monitored through periodic study assessment.
Treatment as Usual | 19 |
| Total | 167 |
Baseline characteristics
| Characteristic | Standard Practice Cognitive-behavioral Therapy | Treatment as Usual | Total | Personalized Cognitive-behavioral Therapy |
|---|---|---|---|---|
| Age, Categorical <=18 years | 71 Participants | 19 Participants | 167 Participants | 77 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10.03 years STANDARD_DEVIATION 1.66 | 10.05 years STANDARD_DEVIATION 1.75 | 9.90 years STANDARD_DEVIATION 1.78 | 9.71 years STANDARD_DEVIATION 1.86 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 10 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 11 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 1 Participants | 5 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 1 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) White | 57 Participants | 13 Participants | 128 Participants | 58 Participants |
| Region of Enrollment United States | 71 participants | 19 participants | 167 participants | 77 participants |
| Sex: Female, Male Female | 12 Participants | 0 Participants | 33 Participants | 21 Participants |
| Sex: Female, Male Male | 59 Participants | 19 Participants | 134 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 71 | 0 / 19 |
| other Total, other adverse events | 0 / 77 | 0 / 71 | 0 / 19 |
| serious Total, serious adverse events | 0 / 77 | 0 / 71 | 0 / 19 |
Outcome results
Primary
Change From Baseline in Anxiety Severity on the Pediatric Anxiety Rating Scale After 16 Weeks of Treatment.
This measure is administered by a clinician and assesses anxiety symptom severity on a scale from 0-25 with higher scores corresponding to worse anxiety.
Time frame: Baseline and After 16 Weeks of Treatment
Population: Not all participants who were randomized to each of the intervention arms completed the Pediatric Anxiety Rating Scale (at baseline and/or post-treatment).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Personalized Cognitive-behavioral Therapy | Change From Baseline in Anxiety Severity on the Pediatric Anxiety Rating Scale After 16 Weeks of Treatment. | Baseline | 3.43 units on a scale | Standard Deviation 0.48 |
| Personalized Cognitive-behavioral Therapy | Change From Baseline in Anxiety Severity on the Pediatric Anxiety Rating Scale After 16 Weeks of Treatment. | Post-treatment | 2.13 units on a scale | Standard Deviation 0.91 |
| Standard Practice Cognitive-behavioral Therapy | Change From Baseline in Anxiety Severity on the Pediatric Anxiety Rating Scale After 16 Weeks of Treatment. | Baseline | 3.47 units on a scale | Standard Deviation 0.47 |
| Standard Practice Cognitive-behavioral Therapy | Change From Baseline in Anxiety Severity on the Pediatric Anxiety Rating Scale After 16 Weeks of Treatment. | Post-treatment | 2.43 units on a scale | Standard Deviation 0.7 |
| Treatment as Usual | Change From Baseline in Anxiety Severity on the Pediatric Anxiety Rating Scale After 16 Weeks of Treatment. | Baseline | 3.28 units on a scale | Standard Deviation 0.39 |
| Treatment as Usual | Change From Baseline in Anxiety Severity on the Pediatric Anxiety Rating Scale After 16 Weeks of Treatment. | Post-treatment | 2.93 units on a scale | Standard Deviation 0.59 |
Secondary
Change From Baseline in Anxiety/Depression Severity on the Child Behavior Checklist After 16 Weeks of Treatment.
The Child Behavior Checklist (CBCL) is completed by parents and the anxiety/depression subscale of the CBCL was used to assess anxiety/depression symptomatology. The CBCL anxiety/depression subscale is rated on a 3-point scale, ranging from 0 (Not true) to 2 (Very True), with higher scores indicating more symptoms.
Time frame: Baseline and After 16 weeks of treatment
Population: Not all participants who were randomized to each of the intervention arms completed the Child Behavior Checklist (at baseline and/or post-treatment).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Personalized Cognitive-behavioral Therapy | Change From Baseline in Anxiety/Depression Severity on the Child Behavior Checklist After 16 Weeks of Treatment. | Baseline | 0.83 units on a scale | Standard Deviation 0.39 |
| Personalized Cognitive-behavioral Therapy | Change From Baseline in Anxiety/Depression Severity on the Child Behavior Checklist After 16 Weeks of Treatment. | Post-treatment | 0.51 units on a scale | Standard Deviation 0.29 |
| Standard Practice Cognitive-behavioral Therapy | Change From Baseline in Anxiety/Depression Severity on the Child Behavior Checklist After 16 Weeks of Treatment. | Baseline | 0.88 units on a scale | Standard Deviation 0.39 |
| Standard Practice Cognitive-behavioral Therapy | Change From Baseline in Anxiety/Depression Severity on the Child Behavior Checklist After 16 Weeks of Treatment. | Post-treatment | 0.69 units on a scale | Standard Deviation 0.34 |
| Treatment as Usual | Change From Baseline in Anxiety/Depression Severity on the Child Behavior Checklist After 16 Weeks of Treatment. | Baseline | 0.73 units on a scale | Standard Deviation 0.28 |
| Treatment as Usual | Change From Baseline in Anxiety/Depression Severity on the Child Behavior Checklist After 16 Weeks of Treatment. | Post-treatment | 0.77 units on a scale | Standard Deviation 0.27 |
Secondary
Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment.
The Childhood Anxiety Impact Scale (CAIS) is a questionnaire completed by parents about the impact of the child's anxiety on functioning in three situational categories (i.e., school, social, and family functioning). The CAIS is rated on a 4-point scale, ranging from 0 (not at all) to 3 (very much). The CAIS items are summed and sorted into 3 subscales, corresponding to each situational category: school, social, and family. For all 3 subscales, higher scores correspond to more associated impact in that area.
Time frame: Baseline and After 16 weeks of treatment
Population: Not all participants who were randomized to each of the intervention arms completed the Childhood Anxiety Impact Scale (at baseline and/or post-treatment).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Personalized Cognitive-behavioral Therapy | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Baseline - CAIS School | 1.38 units on a scale | Standard Deviation 0.61 |
| Personalized Cognitive-behavioral Therapy | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Post - CAIS School | 0.77 units on a scale | Standard Deviation 0.57 |
| Personalized Cognitive-behavioral Therapy | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Baseline - CAIS Social | 0.97 units on a scale | Standard Deviation 0.56 |
| Personalized Cognitive-behavioral Therapy | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Post - CAIS Social | 0.49 units on a scale | Standard Deviation 0.42 |
| Personalized Cognitive-behavioral Therapy | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Baseline - CAIS Family | 1.16 units on a scale | Standard Deviation 0.63 |
| Personalized Cognitive-behavioral Therapy | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Post - CAIS Family | 0.65 units on a scale | Standard Deviation 0.49 |
| Standard Practice Cognitive-behavioral Therapy | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Post - CAIS Family | 0.73 units on a scale | Standard Deviation 0.51 |
| Standard Practice Cognitive-behavioral Therapy | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Baseline - CAIS School | 1.48 units on a scale | Standard Deviation 0.6 |
| Standard Practice Cognitive-behavioral Therapy | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Post - CAIS Social | 0.65 units on a scale | Standard Deviation 0.54 |
| Standard Practice Cognitive-behavioral Therapy | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Baseline - CAIS Family | 1.12 units on a scale | Standard Deviation 0.62 |
| Standard Practice Cognitive-behavioral Therapy | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Post - CAIS School | 0.88 units on a scale | Standard Deviation 0.54 |
| Standard Practice Cognitive-behavioral Therapy | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Baseline - CAIS Social | 0.96 units on a scale | Standard Deviation 0.62 |
| Treatment as Usual | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Post - CAIS School | 1.24 units on a scale | Standard Deviation 0.51 |
| Treatment as Usual | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Baseline - CAIS Social | 0.70 units on a scale | Standard Deviation 0.54 |
| Treatment as Usual | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Post - CAIS Family | 0.88 units on a scale | Standard Deviation 0.6 |
| Treatment as Usual | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Post - CAIS Social | 0.80 units on a scale | Standard Deviation 0.5 |
| Treatment as Usual | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Baseline - CAIS School | 1.19 units on a scale | Standard Deviation 0.7 |
| Treatment as Usual | Change From Baseline in Anxiety Related Impairment as Measured by the Childhood Anxiety Impact Scale After 16 Weeks of Treatment. | Baseline - CAIS Family | 0.98 units on a scale | Standard Deviation 0.44 |
Secondary
Percentage of Participants With Positive Treatment Response as Assessed by the Clinical Global Impressions-Improvement Scale
The Clinical Global Impressions-Improvement scale (CGI-I) was completed by a clinician after 16 weeks of treatment. The CGI-I assesses the severity of anxiety on a 7 point scale, ranging from 1 (very much improved) to 7 (very much worse). A rating of 1 or 2 on the CGI-I designated a positive treatment response.
Time frame: After 16 weeks of treatment
Population: Of the 167 participants assigned to groups, only 145 completed treatment (67 in personalized CBT, 60 in standard CBT, and 18 in treatment as usual). For 3 participants (1 in personalized CBT and 2 in standard CBT), the Clinical Global Impressions-Improvement Scale was not completed at the end of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Personalized Cognitive-behavioral Therapy | Percentage of Participants With Positive Treatment Response as Assessed by the Clinical Global Impressions-Improvement Scale | 92.42 percentage of participants |
| Standard Practice Cognitive-behavioral Therapy | Percentage of Participants With Positive Treatment Response as Assessed by the Clinical Global Impressions-Improvement Scale | 81.03 percentage of participants |
| Treatment as Usual | Percentage of Participants With Positive Treatment Response as Assessed by the Clinical Global Impressions-Improvement Scale | 11.11 percentage of participants |