Translating Neuroprediction Into Precision Medicine Via Brain Priming

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.

Study Overview

• Status: Terminated
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: Oxytocin; Behavioral: Pivotal Response Treatment; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 9 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pivotal Response Treatment (PRT)/oxytocin (OXT) nasal spray; Participants will receive oxytocin nasal spray 45 minutes prior to each PRT session.	Drug: Oxytocin; Oxytocin nasal spray.; Behavioral: Pivotal Response Treatment; An evidence-based manualized treatment for individuals with autism, which was specifically designed to improve social communication.
PLACEBO_COMPARATOR: Pivotal Response Treatment (PRT)/placebo nasal spray; Participants will receive a placebo nasal spray 45 minutes prior to each PRT session.	Behavioral: Pivotal Response Treatment; An evidence-based manualized treatment for individuals with autism, which was specifically designed to improve social communication.; Drug: Placebo; Placebo nasal spray.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Change from Baseline to post-treatment, 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Change from Baseline to post-treatment, 16 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gaze Patterns	Gaze patterns will be tracked using eye tracking technology as participants watch videos for approximately one hour.	Change from Baseline to post-treatment, 16 weeks
Autism Diagnostic Observation Schedule - 2nd Edition (ADOS-2)	The ADOS-2 is a diagnostic assessment for ASD performed by a clinician.	Change from Baseline to post-treatment, 16 weeks
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.	Change from Baseline to post-treatment, 16 weeks
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.	Change from Baseline to post-treatment, 16 weeks
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.	Change from Baseline to post-treatment, 16 weeks
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.	Change from Baseline to post-treatment, 16 weeks
Aberrant Behavior Checklist (ABC)	The ABC is a 58-item parent report behavior rating scale.	Change from Baseline to post-treatment, 16 weeks
Repetitive Behavior Scale - Revised (RBS-R)	The RBS-R is a 49-item, parent report measure of restricted and repetitive behaviors.	Change from Baseline to post-treatment, 16 weeks
Behavior Rating Inventory of Executive Function (BRIEF)	The BRIEF is an 86-item parent report measure of executive function.	Change from Baseline to post-treatment, 16 weeks
Neural Activity/Connectivity During Videos of Biological Motion	Neural activity while viewing videos of biological motion will be measured using fMRI.	Change from Baseline to post-treatment, 16 weeks
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.	Change from Baseline to post-treatment, 16 weeks

Collaborators and Investigators

• Sponsor: Yale University

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 7, 2018
• Primary Completion (ACTUAL): July 28, 2021
• Study Completion (ACTUAL): July 28, 2021

Study Registration Dates

• First Submitted: December 7, 2017
• First Submitted That Met QC Criteria: December 7, 2017
• First Posted (ACTUAL): December 12, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 9, 2022
• Last Update Submitted That Met QC Criteria: August 8, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: 2000021581

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes