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| Name | Class |
|---|---|
| University of Illinois at Chicago | OTHER |
| University of Chicago | OTHER |
| Northwestern University | OTHER |
| Eotvos Lorand University |
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The purpose of this study is to evaluate the feasibility, safety, and preliminary efficacy of integrating targeted dosing of intranasal oxytocin with a social cognitive skills group therapy for school-aged children with autism spectrum disorder (ASD).
The study is a proof-of-concept, combination intervention designed to address individual treatment targets presumed to influence social learning in school-aged children with autism spectrum disorder (ASD). This proposal builds upon prior research on an empirically supported social cognitive skills training curriculum, NETT (Nonverbal communication, Emotion recognition, and Theory of mind Training). NETT is a cognitive-behavioral intervention (CBI) for nonverbal communication, emotion recognition, and theory of mind deficits in youth with ASD. In this two-phase, 3 year, single-blind, contact controlled study, school-aged children with ASD (n=60) will be randomized into a 12-session, parallel group design of Integrated Oxytocin and NETT (ION) or a control social group condition (facilitated play). The study aims to evaluate the safety, tolerability, and efficacy of integrating the neuropeptide, oxytocin (OXT), with the social cognitive curriculum, as well as to identify targets of change and pre-treatment factors predictive of response to ION-ASD. Maintenance of treatment effects will also be assessed 1 month and 3 months post-treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ION-ASD | Experimental | ION-ASD integrates targeted dosing of intranasal oxytocin and social cognitive skills group training curriculum, Seaver-NETT (Nonverbal communication, Emotion recognition, Theory of mind Training). |
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| Facilitated Play | Active Comparator | The active comparison condition is a facilitated play therapy group. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oxytocin | Drug | This is an integrated pharmacological-behavioral intervention targeting social cognitive skills for school-aged children with ASD. Four doses of intranasal oxytocin (24 IUs/dose) will be delivered each week before weekly homework and group therapy sessions. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Social Behavior Impairment (SBI) Composite | The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement. | Baseline and Week 12 (Endpoint) |
| Rate of Change From Baseline in Social Behavior Impairment (SBI) Composite | The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement. | Baseline and Week 12 (Endpoint) |
| Change From Baseline in Social Behavior Impairment (SBI) Composite | The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Responder and Non-responder Participants Based on CGI-I Scores at Week 12 (Endpoint) | Global Functioning will be assessed using the Clinical Global Impressions-Improvement (CGI-I) Scale. A study physician followed standard CGI protocols to evaluate global improvement at each time point based on all available sources of information (e.g., caregiver interviews, behavior rating forms). The CGI-I employs a 7-point scale with the lowest score, 1, indicating the best outcome and the highest score, 7, indicating the worst outcome. Participants receiving scores of 1 (very much improved) or 2 (much improved) were considered responders. Participants receiving scores of 5 (minimally worse), 6 (much worse), or 7 (very much worse) were considered non-responders; note, no participant received a score worse than 5 which was used as the cut-off for non-responders. Participants receiving scores of 3 (minimally improved) or 4 (no change) were considered to show no significant change and omitted from the analysis. |
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Inclusion Criteria
Exclusion Criteria
Patients born prior to 35 weeks gestational age.
Patients with a primary psychiatric diagnosis other than ASD.
Patients with a medical history of neurological disease, including, but not limited to, epilepsy/seizure disorder (except simple febrile seizures), movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes, or known abnormal brain MRI/structural lesion.
Pregnant female patients, sexually active female patients on hormonal birth control and sexually active females who do not use at least two types of non-hormonal birth control.
Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease.
Patients with one or more of the following: hemophilia (bleeding problems, recent nose and brain injuries), abnormal blood pressure (hypotension or hypertension), drug abuse, immunity disorder or severe depression.
Patients who are currently taking oxytocin (OXT) or have taken intranasal oxytocin (IN-OXT) in the past with no response.
Patients who have an Aberrant Behavior Checklist (ABC) Irritability subscale score > 19 at screening
Patients with sensitivity to OXT or any components of its formulation.
Patients unable to tolerate venipuncture procedures for blood sampling.
Patients in foster care for whom the state is defined as a legal guardian.
If they have an arrhythmia present on ECG, that upon consultation with a cardiologist, is deemed to be clinically significant.
Patients with any of the following clinical lab results
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| Name | Affiliation | Role |
|---|---|---|
| Latha Soorya, PhD, BCBA | Rush University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25721186 | Background | Soorya LV, Siper PM, Beck T, Soffes S, Halpern D, Gorenstein M, Kolevzon A, Buxbaum J, Wang AT. Randomized comparative trial of a social cognitive skills group for children with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2015 Mar;54(3):208-216.e1. doi: 10.1016/j.jaac.2014.12.005. Epub 2014 Dec 20. |
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Data from this study may be submitted to the National Database for Autism Research (NDAR), a computer system run by the National Institutes of Health that allows researchers studying autism to collect and share information. Data will be shared with study collaborators as well.
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| ID | Title | Description |
|---|---|---|
| FG000 | ION-ASD | ION-ASD integrates targeted dosing of intranasal oxytocin and social cognitive skills group training curriculum, Seaver-NETT (Nonverbal communication, Emotion recognition, Theory of mind Training). Oxytocin: This is an integrated pharmacological-behavioral intervention targeting social cognitive skills for school-aged children with ASD. Four doses of intranasal oxytocin (24 IUs/dose) will be delivered each week before weekly homework and group therapy sessions. Social Cognitive Skills Training: Social cognitive skills training utilize cognitive behavioral strategies such as problem identification, affective education, performance feedback, and weekly homework activities to target impairments in nonverbal synchrony, emotional expression, and interpretation of intent. The NETT curriculum is manualized and anchored in cognitive behavioral intervention (CBI) strategies, such as problem identification, affective education, performance feedback, and weekly homework activities. Parent education sessions run concurrently with child groups to help facilitate generalization. |
| FG001 | Facilitated Play | The active comparison condition is a facilitated play therapy group. Facilitated Play Therapy: The facilitated play therapy group is a manualized treatment designed to tailor play to the interests and abilities of group members. Therapists use general therapeutics strategies such as reflective functioning statements to foster communication with therapists as well as between peers. Standard educational practices for children with ASD such as visual supports, schedules, and short-directed statements are also used. The concurrent parent group is supportive in nature. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | ION-ASD | ION-ASD integrates targeted dosing of intranasal oxytocin and social cognitive skills group training curriculum, Seaver-NETT (Nonverbal communication, Emotion recognition, Theory of mind Training). Oxytocin: This is an integrated pharmacological-behavioral intervention targeting social cognitive skills for school-aged children with ASD. Four doses of intranasal oxytocin (24 IUs/dose) will be delivered each week before weekly homework and group therapy sessions. Social Cognitive Skills Training: Social cognitive skills training utilize cognitive behavioral strategies such as problem identification, affective education, performance feedback, and weekly homework activities to target impairments in nonverbal synchrony, emotional expression, and interpretation of intent. The NETT curriculum is manualized and anchored in CBI strategies, such as problem identification, affective education, performance feedback, and weekly homework activities. Parent education sessions run concurrently with child groups to help facilitate generalization. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Social Behavior Impairment (SBI) Composite | The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | z-score | Baseline and Week 12 (Endpoint) |
|
24 weeks
Systematic assessment of adverse events (AEs) occurred via trained clinician administration of a safety questionnaire (Adverse Event Form) to caregivers typically every other week beginning at week 1. AEs reported by caregivers' calls outside these visits were recorded as non-systematic. Note all severe AEs were for a single participant in the control (Facilitated Play) group. No AEs were rated as related to study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ION-ASD | ION-ASD integrates targeted dosing of intranasal oxytocin and social cognitive skills group training curriculum, Seaver-NETT (Nonverbal communication, Emotion recognition, Theory of mind Training). Oxytocin: This is an integrated pharmacological-behavioral intervention targeting social cognitive skills for school-aged children with ASD. Four doses of intranasal oxytocin (24 IUs/dose) will be delivered each week before weekly homework and group therapy sessions. Social Cognitive Skills Training: Social cognitive skills training utilize cognitive behavioral strategies such as problem identification, affective education, performance feedback, and weekly homework activities to target impairments in nonverbal synchrony, emotional expression, and interpretation of intent. The NETT curriculum is manualized and anchored in CBI strategies, such as problem identification, affective education, performance feedback, and weekly homework activities. Parent education sessions run concurrently with child groups to help facilitate generalization. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Impulsivity | Psychiatric disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Allergic reaction | Immune system disorders | Systematic Assessment |
Enrollment was slowed down during COVID-19 shut down resulting in the study being under-powered and some groups receiving modified protocols. Apriori secondary analyses of maintenance effects resulted in multiple comparisons tests (i.e., at week 16 and 24) which were not corrected to balance type I/type II errors. Additionally, social cognitive stimuli were not counterbalanced; thus, it's unclear whether social cognitive improvements across groups reflect learning or practice effects.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Latha Valluripalli Soorya | Rush University Medical Center | (312) 942-6238 | latha_soorya@rush.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 8, 2021 | Dec 4, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 8, 2021 | Dec 11, 2023 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 8, 2021 | Dec 4, 2023 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D000067877 | Autism Spectrum Disorder |
| D066107 | Social Skills |
| D009633 | Nonverbal Communication |
| ID | Term |
|---|---|
| D002659 | Child Development Disorders, Pervasive |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
| D012919 | Social Behavior |
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| ID | Term |
|---|---|
| D010121 | Oxytocin |
| ID | Term |
|---|---|
| D010909 | Pituitary Hormones, Posterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
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| OTHER |
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| Social Cognitive Skills Training | Behavioral | Social cognitive skills training utilize cognitive behavioral strategies such as problem identification, affective education, performance feedback, and weekly homework activities to target impairments in nonverbal synchrony, emotional expression, and interpretation of intent. The NETT curriculum is manualized and anchored in CBI strategies, such as problem identification, affective education, performance feedback, and weekly homework activities. Parent education sessions run concurrently with child groups to help facilitate generalization. |
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| Facilitated Play Therapy | Behavioral | The facilitated play therapy group is a manualized treatment designed to tailor play to the interests and abilities of group members. Therapists use general therapeutics strategies such as reflective functioning statements to foster communication with therapists as well as between peers. Standard educational practices for children with ASD such as visual supports, schedules, and short-directed statements are also used. The concurrent parent group is supportive in nature. |
|
| Baseline and Week 16 (1-month follow-up) |
| Rate of Change From Baseline in Social Behavior Impairment (SBI) Composite | The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement. | Baseline and Week 16 (1-month follow-up) |
| Change From Baseline in Social Behavior Impairment (SBI) Composite | The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement. | Baseline and Week 24 (3-month follow-up) |
| Rate of Change From Baseline in Social Behavior Impairment (SBI) Composite | The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement. | Baseline and Week 24 (3-month follow-up) |
| Change From Baseline in Social Cognition (SC) Composite | The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement. | Baseline and Week 12 (Endpoint) |
| Rate of Change From Baseline in Social Cognition (SC) Composite | The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement. | Baseline and Week 12 (Endpoint) |
| Change From Baseline in Social Cognition (SC) Composite | The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement. | Baseline and Week 16 (1-month follow-up) |
| Rate of Change From Baseline in Social Cognition (SC) Composite | The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement. | Baseline and Week 16 (1-month follow-up) |
| Change From Baseline in Social Cognition (SC) Composite | The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement. | Baseline and Week 24 (3-month follow-up) |
| Rate of Change From Baseline in Social Cognition (SC) Composite | The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement. | Baseline and Week 24 (3-month follow-up) |
| Week 12 (Endpoint) |
| Number of Responder and Non-responder Participants Based on CGI-I Scores at Week 16 (1-month Follow-up) | Global Functioning will be assessed using the Clinical Global Impressions-Improvement (CGI-I) Scale. A study physician followed standard CGI protocols to evaluate global improvement at each time point based on all available sources of information (e.g., caregiver interviews, behavior rating forms). The CGI-I employs a 7-point scale with the lowest score, 1, indicating the best outcome and the highest score, 7, indicating the worst outcome. Participants receiving scores of 1 (very much improved) or 2 (much improved) were considered responders. Participants receiving scores of 5 (minimally worse), 6 (much worse), or 7 (very much worse) were considered non-responders; note, no participant received a score worse than 5 which was used as the cut-off for non-responders. Participants receiving scores of 3 (minimally improved) or 4 (no change) were considered to show no significant change and omitted from the analysis. | Week 16 (1-month follow-up) |
| Number of Responder and Non-responder Participants Based on CGI-I Scores at Week 24 (3-month Follow-up) | Global Functioning will be assessed using the Clinical Global Impressions-Improvement (CGI-I) Scale. A study physician followed standard CGI protocols to evaluate global improvement at each time point based on all available sources of information (e.g., caregiver interviews, behavior rating forms). The CGI-I employs a 7-point scale with the lowest score, 1, indicating the best outcome and the highest score, 7, indicating the worst outcome. Participants receiving scores of 1 (very much improved) or 2 (much improved) were considered responders. Participants receiving scores of 5 (minimally worse), 6 (much worse), or 7 (very much worse) were considered non-responders; note, no participant received a score worse than 5 which was used as the cut-off for non-responders . Participants receiving scores of 3 (minimally improved) or 4 (no change) were considered to show no significant change and omitted from the analysis. | Week 24 (3-month follow-up) |
| Change From Baseline in Social Functioning (SRS-2) | The change from baseline in the Social Responsiveness Scale (SRS-2) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The SRS-2 is a caregiver reported measure of social behavior in the general population (3-18 yo) used to assess social functioning. The SRS-2 contains 65 items rated on a 4-point scale (1/not true to 4/almost always true). Scores are recoded 0-3 and totaled for a raw score. Raw scores are converted to T-scores based on age and sex. T-scores have a population mean of 50 with a standard deviation of 10. T-scores 60-65 indicate mild social impairment, 66-75 moderate deficits, and above 76 severe deficits strongly associated with autism. Higher SRS-2 T-scores indicate greater severity of social impairment. Larger, negative slopes reflect a greater reduction in severity. | Baseline and Week 12 (Endpoint) |
| Rate of Change From Baseline in Social Functioning (SRS-2) | The change from baseline in the Social Responsiveness Scale (SRS-2) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The SRS-2 is a caregiver reported measure of social behavior in the general population (3-18 yo) used to assess social functioning. The SRS-2 contains 65 items rated on a 4-point scale (1/not true to 4/almost always true). Scores are recoded 0-3 and totaled for a raw score. Raw scores are converted to T-scores based on age and sex. T-scores have a population mean of 50 with a standard deviation of 10. T-scores 60-65 indicate mild social impairment, 66-75 moderate deficits, and above 76 severe deficits strongly associated with autism. Higher SRS-2 T-scores indicate greater severity of social impairment. Larger, negative slopes reflect a greater reduction in severity. | Baseline and Week 12 (Endpoint) |
| Change From Baseline in Social Functioning (SRS-2) | The change from baseline in the Social Responsiveness Scale (SRS-2) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The SRS-2 is a caregiver reported measure of social behavior in the general population (3-18 yo) used to assess social functioning. The SRS-2 contains 65 items rated on a 4-point scale (1/not true to 4/almost always true). Scores are recoded 0-3 and totaled for a raw score. Raw scores are converted to T-scores based on age and sex. T-scores have a population mean of 50 with a standard deviation of 10. T-scores 60-65 indicate mild social impairment, 66-75 moderate deficits, and above 76 severe deficits strongly associated with autism. Higher SRS-2 T-scores indicate greater severity of social impairment. Larger, negative slopes reflect a greater reduction in severity. | Baseline and Week 16 (1-month follow-up) |
| Rate of Change From Baseline in Social Functioning (SRS-2) | The change from baseline in the Social Responsiveness Scale (SRS-2) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The SRS-2 is a caregiver reported measure of social behavior in the general population (3-18 yo) used to assess social functioning. The SRS-2 contains 65 items rated on a 4-point scale (1/not true to 4/almost always true). Scores are recoded 0-3 and totaled for a raw score. Raw scores are converted to T-scores based on age and sex. T-scores have a population mean of 50 with a standard deviation of 10. T-scores 60-65 indicate mild social impairment, 66-75 moderate deficits, and above 76 severe deficits strongly associated with autism. Higher SRS-2 T-scores indicate greater severity of social impairment. Larger, negative slopes reflect a greater reduction in severity. | Baseline and Week 16 (1-month follow-up) |
| Change From Baseline in Social Functioning (SRS-2) | The change from baseline in the Social Responsiveness Scale (SRS-2) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The SRS-2 is a caregiver reported measure of social behavior in the general population (3-18 yo) used to assess social functioning. The SRS-2 contains 65 items rated on a 4-point scale (1/not true to 4/almost always true). Scores are recoded 0-3 and totaled for a raw score. Raw scores are converted to T-scores based on age and sex. T-scores have a population mean of 50 with a standard deviation of 10. T-scores 60-65 indicate mild social impairment, 66-75 moderate deficits, and above 76 severe deficits strongly associated with autism. Higher SRS-2 T-scores indicate greater severity of social impairment. Larger, negative slopes reflect a greater reduction in severity. | Baseline and Week 24 (3-month follow-up) |
| Rate of Change From Baseline in Social Functioning (SRS-2) | The change from baseline in the Social Responsiveness Scale (SRS-2) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The SRS-2 is a caregiver reported measure of social behavior in the general population (3-18 yo) used to assess social functioning. The SRS-2 contains 65 items rated on a 4-point scale (1/not true to 4/almost always true). Scores are recoded 0-3 and totaled for a raw score. Raw scores are converted to T-scores based on age and sex. T-scores have a population mean of 50 with a standard deviation of 10. T-scores 60-65 indicate mild social impairment, 66-75 moderate deficits, and above 76 severe deficits strongly associated with autism. Higher SRS-2 T-scores indicate greater severity of social impairment. Larger, negative slopes reflect a greater reduction in severity. | Baseline and Week 24 (3-month follow-up) |
| Change From Baseline in Quality of Life (CGSQ) | The change from baseline in the Caregiver Strain Questionnaire (CGSQ) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The CGSQ was used to assess quality of life. The CGSQ is a parent-rated questionnaire designed for parents of children and adolescents with emotional and behavioral disorders. It includes 21 items rated on a 5-point problem scale (1 = not at all to 5 = very much) rating subjective internal, subjective external, and objective strain. A global measure of strain can be calculated by averaging the scores together. Higher CGSQ scores indicate greater strain. Larger, negative slopes reflect a greater reduction in strain (i.e., improvement in score). | Baseline and Week 12 (Endpoint) |
| Rate of Change From Baseline in Quality of Life (CGSQ) | The change from baseline in the Caregiver Strain Questionnaire (CGSQ) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The CGSQ was used to assess quality of life. The CGSQ is a parent-rated questionnaire designed for parents of children and adolescents with emotional and behavioral disorders. It includes 21 items rated on a 5-point problem scale (1 = not at all to 5 = very much) rating subjective internal, subjective external, and objective strain. A global measure of strain can be calculated by averaging the scores together. Higher CGSQ scores indicate greater strain. Larger, negative slopes reflect a greater reduction in strain (i.e., improvement in score). | Baseline and Week 12 (Endpoint) |
| Change From Baseline in Quality of Life (CGSQ) | The change from baseline in the Caregiver Strain Questionnaire (CGSQ) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The CGSQ was used to assess quality of life. The CGSQ is a parent-rated questionnaire designed for parents of children and adolescents with emotional and behavioral disorders. It includes 21 items rated on a 5-point problem scale (1 = not at all to 5 = very much) rating subjective internal, subjective external, and objective strain. A global measure of strain can be calculated by averaging the scores together. Higher CGSQ scores indicate greater strain. Larger, negative slopes reflect a greater reduction in strain (i.e., improvement in score). | Baseline and Week 16 (1-month follow-up) |
| Rate of Change From Baseline in Quality of Life (CGSQ) | The change from baseline in the Caregiver Strain Questionnaire (CGSQ) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The CGSQ was used to assess quality of life. The CGSQ is a parent-rated questionnaire designed for parents of children and adolescents with emotional and behavioral disorders. It includes 21 items rated on a 5-point problem scale (1 = not at all to 5 = very much) rating subjective internal, subjective external, and objective strain. A global measure of strain can be calculated by averaging the scores together. Higher CGSQ scores indicate greater strain. Larger, negative slopes reflect a greater reduction in strain (i.e., improvement in score). | Baseline and Week 16 (1-month follow-up) |
| Change From Baseline in Quality of Life (CGSQ) | The change from baseline in the Caregiver Strain Questionnaire (CGSQ) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The CGSQ was used to assess quality of life. The CGSQ is a parent-rated questionnaire designed for parents of children and adolescents with emotional and behavioral disorders. It includes 21 items rated on a 5-point problem scale (1 = not at all to 5 = very much) rating subjective internal, subjective external, and objective strain. A global measure of strain can be calculated by averaging the scores together. Higher CGSQ scores indicate greater strain. Larger, negative slopes reflect a greater reduction in strain (i.e., improvement in score). | Baseline and Week 24 (3-month follow-up) |
| Rate of Change From Baseline in Quality of Life (CGSQ) | The change from baseline in the Caregiver Strain Questionnaire (CGSQ) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The CGSQ was used to assess quality of life. The CGSQ is a parent-rated questionnaire designed for parents of children and adolescents with emotional and behavioral disorders. It includes 21 items rated on a 5-point problem scale (1 = not at all to 5 = very much) rating subjective internal, subjective external, and objective strain. A global measure of strain can be calculated by averaging the scores together. Higher CGSQ scores indicate greater strain. Larger, negative slopes reflect a greater reduction in strain (i.e., improvement in score). | Baseline and Week 24 (3-month follow-up) |
| BG001 | Facilitated Play | The active comparison condition is a facilitated play therapy group. Facilitated Play Therapy: The facilitated play therapy group is a manualized treatment designed to tailor play to the interests and abilities of group members. Therapists use general therapeutics strategies such as reflective functioning statements to foster communication with therapists as well as between peers. Standard educational practices for children with ASD such as visual supports, schedules, and short-directed statements are also used. The concurrent parent group is supportive in nature. |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| CCC-2 Nonverbal Communication | The Children's Communication Checklist-2 (CCC-2) Nonverbal subscale contains 7 items scored on a 4-point scale (0/less than once a week to 3/every day) for a total range of 0-21; higher total scores reflect greater impairment. Items estimate children's nonverbal communication skills (e.g., eye contact, social distance recognizing other's emotions) and are dispersed in a 70-item parent questionnaire intended for children 4-16-years-old. | Mean | Standard Deviation | units on a scale |
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| CCC-2 Social Relations | The Children's Communication Checklist-2 (CCC-2) Social Relations subscale contains 7 items scored on a 4-point scale (0/less than once a week to 3/every day) for a total range of 0-21; higher total scores reflect greater impairment. Items estimate children's social competence (e.g., comfort around others, sensitivity to and interest in others) and are dispersed in a 70-item parent questionnaire intended for children 4-16-years-old. | Mean | Standard Deviation | units on a scale |
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| Griffith Empathy Measure | The Griffith Empathy Measure (GEM) is a brief parent report survey adapted from an adult empathy measure intended to capture cognitive (i.e., identifying another's situation and taking their perspective) and affective (i.e., responding according to the other's perspective rather than one's own) empathy skills in pre- and through adolescence. Total scores range from -92 to 92, the sum of 23 items scored on a 9-point scale (-4/strongly disagree to 4/strongly agree), with lower total scores reflecting greater impairment. | Mean | Standard Deviation | units on a scale |
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| RMET, % correct | Reading the Mind in the Eyes Test (RMET) % correct out of items administered (maximum 28), participant task | Mean | Standard Deviation | percentage of correct items |
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| DANVA2, % correct | Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2) % correct out of items administered (maximum 96), participant task | Mean | Standard Deviation | percentage of correct items |
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| Verbal IQ | Wechsler Abbreviated Scale of Intelligence, 2nd ed (WASI-II) and Wechsler Intelligence Scale for Children, 4th ed (WISC-IV) are clinician administered intelligence tests. Both tests provide a full scale, non-verbal and verbal intelligence quotient (IQ). Verbal IQ is estimated using the Verbal Comprehension Index (VCI). The WASI-II Vocabulary and Similarities subtests form the VCI. The WISC-IV Vocabulary, Similarity, and Comprehension subtests form the VCI. VCI provides an estimated verbal IQ ranging from 40-160, mean of 100 (standard deviation of 15); higher scores indicate better performance. | Data was missing for one participant's VIQ | Mean | Standard Deviation | units on a scale |
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| ADHD CASI-5 T-score | The Attention Deficit Hyperactivity Disorder (ADHD) combined subscale from the Child & Adolescent Symptom Inventory-5 (CASI-5) measures the frequency of ADHD symptoms in children ages 5-18-years-old. Parents rate the frequency of 18 behavioral items on a 173-item form from 0/never to 3/very often. Items scores are totaled, and raw total subscale scores are converted into ADHD symptom severity T-scores for youth (5-12 yo) by sex. T-scores have a normative mean of 50 (SD=10) with severity categorized as 50-59/low, 60-69/moderate, 70 and above/high indicating clinical impairment. | Mean | Standard Deviation | T-score |
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| Social Responsiveness Scale-2 (SRS-2) | The SRS-2 is a caregiver reported measure of social behavior in the general population (3-18 yo) used to assess social functioning. The SRS-2 contains 65 items rated on a 4-point scale (1/not true to 4/almost always true). Scores are recoded 0-3 and totaled for a raw score. Raw scores convert to T-scores using age and sex. T-scores have a population mean of 50 with a standard deviation of 10. T-scores 60-65 indicate mild social impairment, 66-75 moderate deficits, and above 76 severe deficits strongly associated with autism. Higher SRS-2 T-scores indicate greater severity of social impairment. | Mean | Standard Deviation | T-score |
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| Caregiver Strain Questionnaire-Global Strain (CGSQ) | The CGSQ was used to assess quality of life. The CGSQ is a parent-rated questionnaire designed for parents of children and adolescents with emotional and behavioral disorders. It includes 21 items rated on a 5-point problem scale (1 = not at all to 5 = very much) rating subjective internal, subjective external, and objective strain. A global measure of strain can be calculated by averaging the scores together. Higher CGSQ scores indicate greater strain. | Mean | Standard Deviation | units on a scale |
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| OG000 | ION-ASD | ION-ASD integrates targeted dosing of intranasal oxytocin and social cognitive skills group training curriculum, Seaver-NETT (Nonverbal communication, Emotion recognition, Theory of mind Training). Oxytocin: This is an integrated pharmacological-behavioral intervention targeting social cognitive skills for school-aged children with ASD. Four doses of intranasal oxytocin (24 IUs/dose) will be delivered each week before weekly homework and group therapy sessions. Social Cognitive Skills Training: Social cognitive skills training utilize cognitive behavioral strategies such as problem identification, affective education, performance feedback, and weekly homework activities to target impairments in nonverbal synchrony, emotional expression, and interpretation of intent. The NETT curriculum is manualized and anchored in CBI strategies, such as problem identification, affective education, performance feedback, and weekly homework activities. Parent education sessions run concurrently with child groups to help facilitate generalization. |
| OG001 | Facilitated Play | The active comparison condition is a facilitated play therapy group. Facilitated Play Therapy: The facilitated play therapy group is a manualized treatment designed to tailor play to the interests and abilities of group members. Therapists use general therapeutics strategies such as reflective functioning statements to foster communication with therapists as well as between peers. Standard educational practices for children with ASD such as visual supports, schedules, and short-directed statements are also used. The concurrent parent group is supportive in nature. |
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| Primary | Rate of Change From Baseline in Social Behavior Impairment (SBI) Composite | The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | scores/week | Baseline and Week 12 (Endpoint) |
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| Primary | Change From Baseline in Social Behavior Impairment (SBI) Composite | The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | z-score | Baseline and Week 16 (1-month follow-up) |
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| Primary | Rate of Change From Baseline in Social Behavior Impairment (SBI) Composite | The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | scores/week | Baseline and Week 16 (1-month follow-up) |
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| Primary | Change From Baseline in Social Behavior Impairment (SBI) Composite | The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | z-score | Baseline and Week 24 (3-month follow-up) |
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| Primary | Rate of Change From Baseline in Social Behavior Impairment (SBI) Composite | The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | scores/week | Baseline and Week 24 (3-month follow-up) |
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| Primary | Change From Baseline in Social Cognition (SC) Composite | The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | z-score | Baseline and Week 12 (Endpoint) |
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| Primary | Rate of Change From Baseline in Social Cognition (SC) Composite | The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | scores/week | Baseline and Week 12 (Endpoint) |
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| Primary | Change From Baseline in Social Cognition (SC) Composite | The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | z-score | Baseline and Week 16 (1-month follow-up) |
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| Primary | Rate of Change From Baseline in Social Cognition (SC) Composite | The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | scores/week | Baseline and Week 16 (1-month follow-up) |
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| Primary | Change From Baseline in Social Cognition (SC) Composite | The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | z-score | Baseline and Week 24 (3-month follow-up) |
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| Primary | Rate of Change From Baseline in Social Cognition (SC) Composite | The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | scores/week | Baseline and Week 24 (3-month follow-up) |
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| Secondary | Number of Responder and Non-responder Participants Based on CGI-I Scores at Week 12 (Endpoint) | Global Functioning will be assessed using the Clinical Global Impressions-Improvement (CGI-I) Scale. A study physician followed standard CGI protocols to evaluate global improvement at each time point based on all available sources of information (e.g., caregiver interviews, behavior rating forms). The CGI-I employs a 7-point scale with the lowest score, 1, indicating the best outcome and the highest score, 7, indicating the worst outcome. Participants receiving scores of 1 (very much improved) or 2 (much improved) were considered responders. Participants receiving scores of 5 (minimally worse), 6 (much worse), or 7 (very much worse) were considered non-responders; note, no participant received a score worse than 5 which was used as the cut-off for non-responders. Participants receiving scores of 3 (minimally improved) or 4 (no change) were considered to show no significant change and omitted from the analysis. | If participants were missing CGI-I ratings at week 12 (Facilitated Play: n=2), the rating from the last available visit (i.e., week 6) was used. Participants with scores of 3 or 4, indicating no significant change, were not included in the responder analyses (ION-ASD: n=12; Facilitated Play: n=12). One participant (Facilitated Play) had no data to carry forward. Additionally, two participants dropped out of the study (ION-ASD: n=1; Facilitated Play: n=1) and were excluded from the analyses. | Posted | Count of Participants | Participants | Week 12 (Endpoint) |
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| Secondary | Number of Responder and Non-responder Participants Based on CGI-I Scores at Week 16 (1-month Follow-up) | Global Functioning will be assessed using the Clinical Global Impressions-Improvement (CGI-I) Scale. A study physician followed standard CGI protocols to evaluate global improvement at each time point based on all available sources of information (e.g., caregiver interviews, behavior rating forms). The CGI-I employs a 7-point scale with the lowest score, 1, indicating the best outcome and the highest score, 7, indicating the worst outcome. Participants receiving scores of 1 (very much improved) or 2 (much improved) were considered responders. Participants receiving scores of 5 (minimally worse), 6 (much worse), or 7 (very much worse) were considered non-responders; note, no participant received a score worse than 5 which was used as the cut-off for non-responders. Participants receiving scores of 3 (minimally improved) or 4 (no change) were considered to show no significant change and omitted from the analysis. | If participants were missing CGI-I ratings at week 16 (ION-ASD: n=1; Facilitated Play: n=5), the rating from the last available visit (i.e., 5 from week 12 and 1 from week 6) was used. Participants with scores of 3 or 4, indicating no significant change, were not included in the responder analyses (ION-ASD: n=10; Facilitated Play: n=12). Additionally, from baseline to week 16, five participants dropped out of the study (ION-ASD: n=3; Facilitated Play: n=2) and were excluded from the analyses. | Posted | Count of Participants | Participants | Week 16 (1-month follow-up) |
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| Secondary | Number of Responder and Non-responder Participants Based on CGI-I Scores at Week 24 (3-month Follow-up) | Global Functioning will be assessed using the Clinical Global Impressions-Improvement (CGI-I) Scale. A study physician followed standard CGI protocols to evaluate global improvement at each time point based on all available sources of information (e.g., caregiver interviews, behavior rating forms). The CGI-I employs a 7-point scale with the lowest score, 1, indicating the best outcome and the highest score, 7, indicating the worst outcome. Participants receiving scores of 1 (very much improved) or 2 (much improved) were considered responders. Participants receiving scores of 5 (minimally worse), 6 (much worse), or 7 (very much worse) were considered non-responders; note, no participant received a score worse than 5 which was used as the cut-off for non-responders . Participants receiving scores of 3 (minimally improved) or 4 (no change) were considered to show no significant change and omitted from the analysis. | If participants were missing CGI-I ratings at week 24 (ION-ASD: n=2), the rating from the last available visit (i.e., week 16) was used. Participants with scores of 3 or 4, indicating no significant change, were not included in the responder analyses (ION-ASD: n=6; Facilitated Play: n=11). Additionally, from baseline to week 24, seven participants dropped out of the study (ION-ASD: n=4; Facilitated Play: n=3) and were therefore excluded from the analyses. | Posted | Count of Participants | Participants | Week 24 (3-month follow-up) |
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| Secondary | Change From Baseline in Social Functioning (SRS-2) | The change from baseline in the Social Responsiveness Scale (SRS-2) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The SRS-2 is a caregiver reported measure of social behavior in the general population (3-18 yo) used to assess social functioning. The SRS-2 contains 65 items rated on a 4-point scale (1/not true to 4/almost always true). Scores are recoded 0-3 and totaled for a raw score. Raw scores are converted to T-scores based on age and sex. T-scores have a population mean of 50 with a standard deviation of 10. T-scores 60-65 indicate mild social impairment, 66-75 moderate deficits, and above 76 severe deficits strongly associated with autism. Higher SRS-2 T-scores indicate greater severity of social impairment. Larger, negative slopes reflect a greater reduction in severity. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | T-score | Baseline and Week 12 (Endpoint) |
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| Secondary | Rate of Change From Baseline in Social Functioning (SRS-2) | The change from baseline in the Social Responsiveness Scale (SRS-2) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The SRS-2 is a caregiver reported measure of social behavior in the general population (3-18 yo) used to assess social functioning. The SRS-2 contains 65 items rated on a 4-point scale (1/not true to 4/almost always true). Scores are recoded 0-3 and totaled for a raw score. Raw scores are converted to T-scores based on age and sex. T-scores have a population mean of 50 with a standard deviation of 10. T-scores 60-65 indicate mild social impairment, 66-75 moderate deficits, and above 76 severe deficits strongly associated with autism. Higher SRS-2 T-scores indicate greater severity of social impairment. Larger, negative slopes reflect a greater reduction in severity. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | scores/week | Baseline and Week 12 (Endpoint) |
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| Secondary | Change From Baseline in Social Functioning (SRS-2) | The change from baseline in the Social Responsiveness Scale (SRS-2) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The SRS-2 is a caregiver reported measure of social behavior in the general population (3-18 yo) used to assess social functioning. The SRS-2 contains 65 items rated on a 4-point scale (1/not true to 4/almost always true). Scores are recoded 0-3 and totaled for a raw score. Raw scores are converted to T-scores based on age and sex. T-scores have a population mean of 50 with a standard deviation of 10. T-scores 60-65 indicate mild social impairment, 66-75 moderate deficits, and above 76 severe deficits strongly associated with autism. Higher SRS-2 T-scores indicate greater severity of social impairment. Larger, negative slopes reflect a greater reduction in severity. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | T-score | Baseline and Week 16 (1-month follow-up) |
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| Secondary | Rate of Change From Baseline in Social Functioning (SRS-2) | The change from baseline in the Social Responsiveness Scale (SRS-2) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The SRS-2 is a caregiver reported measure of social behavior in the general population (3-18 yo) used to assess social functioning. The SRS-2 contains 65 items rated on a 4-point scale (1/not true to 4/almost always true). Scores are recoded 0-3 and totaled for a raw score. Raw scores are converted to T-scores based on age and sex. T-scores have a population mean of 50 with a standard deviation of 10. T-scores 60-65 indicate mild social impairment, 66-75 moderate deficits, and above 76 severe deficits strongly associated with autism. Higher SRS-2 T-scores indicate greater severity of social impairment. Larger, negative slopes reflect a greater reduction in severity. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | scores/week | Baseline and Week 16 (1-month follow-up) |
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| Secondary | Change From Baseline in Social Functioning (SRS-2) | The change from baseline in the Social Responsiveness Scale (SRS-2) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The SRS-2 is a caregiver reported measure of social behavior in the general population (3-18 yo) used to assess social functioning. The SRS-2 contains 65 items rated on a 4-point scale (1/not true to 4/almost always true). Scores are recoded 0-3 and totaled for a raw score. Raw scores are converted to T-scores based on age and sex. T-scores have a population mean of 50 with a standard deviation of 10. T-scores 60-65 indicate mild social impairment, 66-75 moderate deficits, and above 76 severe deficits strongly associated with autism. Higher SRS-2 T-scores indicate greater severity of social impairment. Larger, negative slopes reflect a greater reduction in severity. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | T-score | Baseline and Week 24 (3-month follow-up) |
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| Secondary | Rate of Change From Baseline in Social Functioning (SRS-2) | The change from baseline in the Social Responsiveness Scale (SRS-2) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The SRS-2 is a caregiver reported measure of social behavior in the general population (3-18 yo) used to assess social functioning. The SRS-2 contains 65 items rated on a 4-point scale (1/not true to 4/almost always true). Scores are recoded 0-3 and totaled for a raw score. Raw scores are converted to T-scores based on age and sex. T-scores have a population mean of 50 with a standard deviation of 10. T-scores 60-65 indicate mild social impairment, 66-75 moderate deficits, and above 76 severe deficits strongly associated with autism. Higher SRS-2 T-scores indicate greater severity of social impairment. Larger, negative slopes reflect a greater reduction in severity. | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | scores/week | Baseline and Week 24 (3-month follow-up) |
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| Secondary | Change From Baseline in Quality of Life (CGSQ) | The change from baseline in the Caregiver Strain Questionnaire (CGSQ) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The CGSQ was used to assess quality of life. The CGSQ is a parent-rated questionnaire designed for parents of children and adolescents with emotional and behavioral disorders. It includes 21 items rated on a 5-point problem scale (1 = not at all to 5 = very much) rating subjective internal, subjective external, and objective strain. A global measure of strain can be calculated by averaging the scores together. Higher CGSQ scores indicate greater strain. Larger, negative slopes reflect a greater reduction in strain (i.e., improvement in score). | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | units on a scale | Baseline and Week 12 (Endpoint) |
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| Secondary | Rate of Change From Baseline in Quality of Life (CGSQ) | The change from baseline in the Caregiver Strain Questionnaire (CGSQ) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The CGSQ was used to assess quality of life. The CGSQ is a parent-rated questionnaire designed for parents of children and adolescents with emotional and behavioral disorders. It includes 21 items rated on a 5-point problem scale (1 = not at all to 5 = very much) rating subjective internal, subjective external, and objective strain. A global measure of strain can be calculated by averaging the scores together. Higher CGSQ scores indicate greater strain. Larger, negative slopes reflect a greater reduction in strain (i.e., improvement in score). | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | units on a scale/week | Baseline and Week 12 (Endpoint) |
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| Secondary | Change From Baseline in Quality of Life (CGSQ) | The change from baseline in the Caregiver Strain Questionnaire (CGSQ) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The CGSQ was used to assess quality of life. The CGSQ is a parent-rated questionnaire designed for parents of children and adolescents with emotional and behavioral disorders. It includes 21 items rated on a 5-point problem scale (1 = not at all to 5 = very much) rating subjective internal, subjective external, and objective strain. A global measure of strain can be calculated by averaging the scores together. Higher CGSQ scores indicate greater strain. Larger, negative slopes reflect a greater reduction in strain (i.e., improvement in score). | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | units on a scale | Baseline and Week 16 (1-month follow-up) |
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| Secondary | Rate of Change From Baseline in Quality of Life (CGSQ) | The change from baseline in the Caregiver Strain Questionnaire (CGSQ) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The CGSQ was used to assess quality of life. The CGSQ is a parent-rated questionnaire designed for parents of children and adolescents with emotional and behavioral disorders. It includes 21 items rated on a 5-point problem scale (1 = not at all to 5 = very much) rating subjective internal, subjective external, and objective strain. A global measure of strain can be calculated by averaging the scores together. Higher CGSQ scores indicate greater strain. Larger, negative slopes reflect a greater reduction in strain (i.e., improvement in score). | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | units on a scale/week | Baseline and Week 16 (1-month follow-up) |
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| Secondary | Change From Baseline in Quality of Life (CGSQ) | The change from baseline in the Caregiver Strain Questionnaire (CGSQ) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The CGSQ was used to assess quality of life. The CGSQ is a parent-rated questionnaire designed for parents of children and adolescents with emotional and behavioral disorders. It includes 21 items rated on a 5-point problem scale (1 = not at all to 5 = very much) rating subjective internal, subjective external, and objective strain. A global measure of strain can be calculated by averaging the scores together. Higher CGSQ scores indicate greater strain. Larger, negative slopes reflect a greater reduction in strain (i.e., improvement in score). | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | units on a scale | Baseline and Week 24 (3-month follow-up) |
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| Secondary | Rate of Change From Baseline in Quality of Life (CGSQ) | The change from baseline in the Caregiver Strain Questionnaire (CGSQ) is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group*time interaction. The CGSQ was used to assess quality of life. The CGSQ is a parent-rated questionnaire designed for parents of children and adolescents with emotional and behavioral disorders. It includes 21 items rated on a 5-point problem scale (1 = not at all to 5 = very much) rating subjective internal, subjective external, and objective strain. A global measure of strain can be calculated by averaging the scores together. Higher CGSQ scores indicate greater strain. Larger, negative slopes reflect a greater reduction in strain (i.e., improvement in score). | All participants contributed to the intent to treat (ITT) model. | Posted | Mean | Standard Error | units on a scale/week | Baseline and Week 24 (3-month follow-up) |
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| 0 |
| 20 |
| 0 |
| 20 |
| 20 |
| 20 |
| EG001 | Facilitated Play | The active comparison condition is a facilitated play therapy group. Facilitated Play Therapy: The facilitated play therapy group is a manualized treatment designed to tailor play to the interests and abilities of group members. Therapists use general therapeutics strategies such as reflective functioning statements to foster communication with therapists as well as between peers. Standard educational practices for children with ASD such as visual supports, schedules, and short-directed statements are also used. The concurrent parent group is supportive in nature. | 0 | 20 | 1 | 20 | 20 | 20 |
| Aggression | Psychiatric disorders | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | Non-systematic Assessment |
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| Irritable | Psychiatric disorders | Systematic Assessment |
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| Mood lability | Psychiatric disorders | Systematic Assessment |
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| Ear pain | Ear and labyrinth disorders | Systematic Assessment |
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| Visual change | Eye disorders | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Change in appetite | Gastrointestinal disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Cramping | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Indigestion | Gastrointestinal disorders | Systematic Assessment |
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| Large and frequent stools | Gastrointestinal disorders | Systematic Assessment |
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| Loose stools | Gastrointestinal disorders | Systematic Assessment |
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| Nausea/vomitting | Gastrointestinal disorders | Systematic Assessment |
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| Change in sleep | General disorders | Systematic Assessment |
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| Change in speech | General disorders | Systematic Assessment |
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| Fever | Infections and infestations | Systematic Assessment |
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| Infection | Infections and infestations | Systematic Assessment |
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| Loss of tooth | Infections and infestations | Systematic Assessment |
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| Toothache | Infections and infestations | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Joint pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Muscle ache | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Clumsy | Nervous system disorders | Systematic Assessment |
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| Dizziness | Nervous system disorders | Systematic Assessment |
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| Fatigue | Nervous system disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Hyperactivity/Impulsivity | Psychiatric disorders | Systematic Assessment |
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| Staring episode | Nervous system disorders | Systematic Assessment |
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| Abnormal thoughts | Psychiatric disorders | Systematic Assessment |
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| Aggression | Psychiatric disorders | Systematic Assessment |
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| Anxiety | Psychiatric disorders | Systematic Assessment |
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| Confused | Psychiatric disorders | Systematic Assessment |
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| Depression | Psychiatric disorders | Systematic Assessment |
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| Irritable | Psychiatric disorders | Systematic Assessment |
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| Mood lability | Psychiatric disorders | Systematic Assessment |
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| Poor Concentration | Psychiatric disorders | Systematic Assessment |
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| Nose picking | Psychiatric disorders | Systematic Assessment |
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| Pulling on lip skin | Psychiatric disorders | Systematic Assessment |
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| Repetitive behavior/speech | Psychiatric disorders | Systematic Assessment |
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| Sassy - talking back | Psychiatric disorders | Systematic Assessment |
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| Self-injurious behavior | Psychiatric disorders | Systematic Assessment |
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| Fingernail picking | Psychiatric disorders | Systematic Assessment |
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| Hair pulling | Psychiatric disorders | Systematic Assessment |
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| Skin picking | Psychiatric disorders | Systematic Assessment |
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| Stereotypic movement | Psychiatric disorders | Systematic Assessment |
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| Suicidal thoughts | Psychiatric disorders | Systematic Assessment |
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| Tearful | Psychiatric disorders | Systematic Assessment |
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| Tics | Psychiatric disorders | Systematic Assessment |
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| Enuresis | Renal and urinary disorders | Systematic Assessment |
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| Polydipsia, polyuria | Renal and urinary disorders | Systematic Assessment |
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| Clearing throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Runny nose | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Shortness of breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Sore throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Wheezing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Flu | Infections and infestations | Systematic Assessment |
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| Low self esteem | Psychiatric disorders | Systematic Assessment |
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| Odynophagia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Itching | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Social withdrawal | Social circumstances | Systematic Assessment |
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| Visual change | Eye disorders | Non-systematic Assessment |
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| Indigestion | Gastrointestinal disorders | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment |
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| Poor concentration | Nervous system disorders | Non-systematic Assessment |
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| Repetitive behavior/speech | Psychiatric disorders | Non-systematic Assessment |
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| Stereotypic movement | Psychiatric disorders | Non-systematic Assessment |
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| Increase in flatulence | Gastrointestinal disorders | Systematic Assessment |
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| Upper respiratory infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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Not provided
Not provided
| D001519 | Behavior |
| D003142 | Communication |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
|