Autism Spectrum Disorder
Conditions
Brief summary
The present study examines the impact of oxytocin (OXT) and Pivotal Response Treatment (PRT) on the development of language, social, and play skills in young children with Autism Spectrum Disorder (ASD). The purpose of this study is to examine the impact of OXT as an enhancer of response to PRT. Participants will be randomly assigned to either an intranasal OXT group or a placebo group. Neither the research team nor the participants will know or choose which group the participant is assigned to. Children in both groups will participate in a 16-week trial of PRT. The trial will test the hypothesis that children with lower levels of activity in and functional connectivity among certain PRT-response brain regions will benefit more from the administration of OXT vs. placebo as an enhancer to a 16-week trial of PRT.
Detailed description
This project investigates the effectiveness of a new intervention approach for Autism Spectrum Disorder (ASD) to optimize the effects of an evidence-based behavioral intervention, Pivotal Response Treatment (PRT) by attempting to enhance it with oxytocin (OXT). We will integrate fMRI, eye tracking, and behavioral outcomes to measure how OXT may create a neural background for individuals with ASD to bolster their motivation to interact socially and facilitate their biological preparedness for learning social communication skills during behavioral treatments.
Interventions
DRUGOxytocin
Oxytocin nasal spray.
BEHAVIORALPivotal Response Treatment
An evidence-based manualized treatment for individuals with autism, which was specifically designed to improve social communication.
DRUGPlacebo
Placebo nasal spray.
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Eighty children will be randomly assigned to receive PRT with either oxytocin (forty children) or a placebo (forty children).
Eligibility
Sex/Gender
ALL
Age
5 Years to 9 Years
Healthy volunteers
No
Inclusion criteria
1. Fit the age requirement: age 5-9 2. Have been diagnosed previously with an ASD and meet criteria for ASD when characterized by research team 3. Be in good medical health 4. Be cooperative with testing 5. Speak English in the family 6. Successfully complete an fMRI scan 7. Full-scale intelligence quotient (IQ)\>70
Exclusion criteria
1. Any metal or electromagnetic implants, including: 1. Cardiac pacemaker 2. Defibrillator 3. Artificial heart valve 4. Aneurysm clip 5. Cochlear implants 6. Shrapnel 7. Neurostimulators 8. History of metal fragments in eyes or skin 2. Significant hearing loss or other severe sensory impairment 3. A fragile health status. 4. Current use of prescription psychotropic medications that may affect cognitive processes under study. 5. A history of significant head trauma or serious brain or psychiatric illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Social Responsiveness Scale, 2nd Edition (SRS-2) | Change from Baseline to post-treatment, 16 weeks | The SRS-2 is a 65-item measure of social responsiveness. The SRS-2 is filled out by a parent. The SRS-2 has a minimum raw score of 0 and a maximum raw score of 195. Higher raw scores on the SRS-2 mean a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vineland Adaptive Behavior Scale, 3rd Edition (Vineland-III) | Change from Baseline to post-treatment, 16 weeks | The Vineland-III is a parent interview administered by a member of the research team. The interview lasts approximately one hour and measures four domains of the child's adaptive behavior. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impressions - Severity (CGI-S) | Change from Baseline to post-treatment, 16 weeks | The CGI-S is a 7-point Likert Scale completed by a clinician, which measures clinical impressions of symptom severity. |
| Social Responsiveness Scale - 2 (Teacher Form) | Change from Baseline to post-treatment, 16 weeks | The SRS-2 is a 65-item measure of social responsiveness. The SRS-2 Teacher is filled out by the participant's teacher. |
| Child Behavior Checklist (CBCL) | Change from Baseline to post-treatment, 16 weeks | The CBCL is a parent report measure of problem behaviors. The form for children ages 1.5-5 has 100 items, and the form for children ages 6-18 has 113 items. |
| Child and Adolescent Symptom Inventory - 5 (CASI-5) | Change from Baseline to post-treatment, 16 weeks | The CASI-5 is a behavior inventory measuring symptoms of several mental health problems among children. The CASI-5 is a 173-item parent report measure. |
| Gaze Patterns | Change from Baseline to post-treatment, 16 weeks | Gaze patterns will be tracked using eye tracking technology as participants watch videos for approximately one hour. |
| Repetitive Behavior Scale - Revised (RBS-R) | Change from Baseline to post-treatment, 16 weeks | The RBS-R is a 49-item, parent report measure of restricted and repetitive behaviors. |
| Behavior Rating Inventory of Executive Function (BRIEF) | Change from Baseline to post-treatment, 16 weeks | The BRIEF is an 86-item parent report measure of executive function. |
| Neural Activity/Connectivity During Videos of Biological Motion | Change from Baseline to post-treatment, 16 weeks | Neural activity while viewing videos of biological motion will be measured using fMRI. |
| Brief Observation of Social Communication Change (BOSCC) | Change from Baseline to post-treatment, 16 weeks | The BOSCC is a coding scheme that measures social communication change. Codes are based on videos of play session between children and parents. |
| Aberrant Behavior Checklist (ABC) | Change from Baseline to post-treatment, 16 weeks | The ABC is a 58-item parent report behavior rating scale. |
| Autism Diagnostic Observation Schedule - 2nd Edition (ADOS-2) | Change from Baseline to post-treatment, 16 weeks | The ADOS-2 is a diagnostic assessment for ASD performed by a clinician. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pivotal Response Treatment (PRT)/Oxytocin (OXT) Nasal Spray Participants will receive oxytocin nasal spray 45 minutes prior to each PRT session.
Oxytocin: Oxytocin nasal spray.
Pivotal Response Treatment: An evidence-based manualized treatment for individuals with autism, which was specifically designed to improve social communication. | 3 |
| Pivotal Response Treatment (PRT)/Placebo Nasal Spray Participants will receive a placebo nasal spray 45 minutes prior to each PRT session.
Pivotal Response Treatment: An evidence-based manualized treatment for individuals with autism, which was specifically designed to improve social communication.
Placebo: Placebo nasal spray. | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | COVID-19 | 2 | 0 |
Baseline characteristics
| Characteristic | Pivotal Response Treatment (PRT)/Oxytocin (OXT) Nasal Spray | Total | Pivotal Response Treatment (PRT)/Placebo Nasal Spray |
|---|---|---|---|
| Age, Continuous | 71 Months | 76 Months | 82 Months |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment United States | 3 participants | 5 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 0 / 3 | 0 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 |
Outcome results
Primary
Social Responsiveness Scale, 2nd Edition (SRS-2)
The SRS-2 is a 65-item measure of social responsiveness. The SRS-2 is filled out by a parent. The SRS-2 has a minimum raw score of 0 and a maximum raw score of 195. Higher raw scores on the SRS-2 mean a worse outcome.
Time frame: Change from Baseline to post-treatment, 16 weeks
Population: Only 1/3 participants completed treatment in the oxytocin group. Therefore, the mean raw score for the oxytocin group is based off of that subject's data only.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pivotal Response Treatment (PRT)/Oxytocin (OXT) Nasal Spray | Social Responsiveness Scale, 2nd Edition (SRS-2) | 39 score on a scale |
| Pivotal Response Treatment (PRT)/Placebo Nasal Spray | Social Responsiveness Scale, 2nd Edition (SRS-2) | -16 score on a scale |
Secondary
Vineland Adaptive Behavior Scale, 3rd Edition (Vineland-III)
The Vineland-III is a parent interview administered by a member of the research team. The interview lasts approximately one hour and measures four domains of the child's adaptive behavior.
Time frame: Change from Baseline to post-treatment, 16 weeks
Population: Data were not collected due to COVID-19 related termination of study.
Other Pre-specified
Aberrant Behavior Checklist (ABC)
The ABC is a 58-item parent report behavior rating scale.
Time frame: Change from Baseline to post-treatment, 16 weeks
Population: Data were not collected due to COVID-19 related termination of study.
Other Pre-specified
Autism Diagnostic Observation Schedule - 2nd Edition (ADOS-2)
The ADOS-2 is a diagnostic assessment for ASD performed by a clinician.
Time frame: Change from Baseline to post-treatment, 16 weeks
Population: Data were not collected due to COVID-19 related termination of study.
Other Pre-specified
Behavior Rating Inventory of Executive Function (BRIEF)
The BRIEF is an 86-item parent report measure of executive function.
Time frame: Change from Baseline to post-treatment, 16 weeks
Population: Data were not collected due to COVID-19 related termination of study.
Other Pre-specified
Brief Observation of Social Communication Change (BOSCC)
The BOSCC is a coding scheme that measures social communication change. Codes are based on videos of play session between children and parents.
Time frame: Change from Baseline to post-treatment, 16 weeks
Population: Data were not collected due to COVID-19 related termination of study.
Other Pre-specified
Child and Adolescent Symptom Inventory - 5 (CASI-5)
The CASI-5 is a behavior inventory measuring symptoms of several mental health problems among children. The CASI-5 is a 173-item parent report measure.
Time frame: Change from Baseline to post-treatment, 16 weeks
Population: Data were not collected due to COVID-19 related termination of study.
Other Pre-specified
Child Behavior Checklist (CBCL)
The CBCL is a parent report measure of problem behaviors. The form for children ages 1.5-5 has 100 items, and the form for children ages 6-18 has 113 items.
Time frame: Change from Baseline to post-treatment, 16 weeks
Population: Data were not collected due to COVID-19 related termination of study.
Other Pre-specified
Clinical Global Impressions - Severity (CGI-S)
The CGI-S is a 7-point Likert Scale completed by a clinician, which measures clinical impressions of symptom severity.
Time frame: Change from Baseline to post-treatment, 16 weeks
Population: Data were not collected due to COVID-19 related termination of study.
Other Pre-specified
Gaze Patterns
Gaze patterns will be tracked using eye tracking technology as participants watch videos for approximately one hour.
Time frame: Change from Baseline to post-treatment, 16 weeks
Population: Data were not collected due to COVID-19 related termination of study.
Other Pre-specified
Neural Activity/Connectivity During Videos of Biological Motion
Neural activity while viewing videos of biological motion will be measured using fMRI.
Time frame: Change from Baseline to post-treatment, 16 weeks
Population: Data were not collected due to COVID-19 related termination of study.
Other Pre-specified
Repetitive Behavior Scale - Revised (RBS-R)
The RBS-R is a 49-item, parent report measure of restricted and repetitive behaviors.
Time frame: Change from Baseline to post-treatment, 16 weeks
Population: Data were not collected due to COVID-19 related termination of study.
Other Pre-specified
Social Responsiveness Scale - 2 (Teacher Form)
The SRS-2 is a 65-item measure of social responsiveness. The SRS-2 Teacher is filled out by the participant's teacher.
Time frame: Change from Baseline to post-treatment, 16 weeks
Population: Data were not collected due to COVID-19 related termination of study.