Clinical trial NCT01624194: Intranasal Oxytocin Treatment for Social Deficits in Children With Autism
Official title: Double-blind, Randomized, Placebo Controlled Trial of Intranasal Oxytocin Treatment for Social Deficits in Children With Autism.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autism
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2012-06-20
Enrollment: 54
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Autism is a pervasive developmental disorder characterized by core deficits in social behavior and communication, and the presence of repetitive or stereotyped behaviors. It is one of three recognized disorders in the autism spectrum which affects an estimated 1 in 88 children in the United States. At present, pharmacotherapies target only associated features of autism, with no effective drug treatments for the social impairments. Several lines of evidence now suggest that the neuropeptide oxytocin (OT) may be an effective treatment for the core social deficits in autism. Here we will test the effects of twice daily intranasal OT (24 IU) over a 4-week period for enhancing social deficits in male and female children aged 6-12 years with autism. This research has high potential to lead to the development of more effective treatments and earlier interventions for children with autism.

Detailed description: In recent years, the neuropeptide oxytocin (OT) has been implicated in a wide range of social behaviors including attachment bonds, emotion recognition, eye gaze to social cues, and memory for social information. Social impairments represent one of the most intractable features of autism, and evidence now suggests that OT biology is dysregulated in individuals with this disorder. The central aim of the research outlined here is to test whether OT administration to children with autism increases their quality and quantity of social interactions and enhances their ability to process emotional and social information. Findings from initial single-dose OT administration studies in teenaged and adult males with autism have shown improvement in some aspects of social functioning, but replication and extension to well-controlled treatment trials with younger male and female subjects is necessary to evaluate effectiveness. We therefore aim to investigate the effect of intranasal OT on social cognition and behavior immediately following a single-dose (24IU) and following a 4-week period of OT (24IU BID) administration in a sample of 50 subjects with autism aged 6 to 12 years. The primary outcome for this study is change in social behavior, as determined by parent ratings on the Social Responsiveness Scale (SRS) after the 4-week treatment period. Secondary outcomes are changes in functioning on laboratory-based measures of social behavior and cognition following single-dose and 4-week OT administration. Research in a small study sample (N=13) also identified treatment responders and non-responders to a single-dose of OT. Thus, we also aim to identify biological and cognitive and behavioral variables (i.e., pretreatment levels of social functioning and pretreatment plasma hormone levels) that may influence treatment response efficacy in our larger study sample. On completion of the 4-week treatment period all subjects will have the option of participating in another 4-week double-blind trial in which they will be switched to the alternate nasal spray to that which they previously received. They will then undergo a fourth and final assessment time-point using the same testing procedures as outlined above on completion of the 4-week dosing. By providing subjects with the option of participating in a second 4-week treatment trial, all subjects will have an opportunity to receive the active oxytocin nasal spray. We also will be able to examine any ongoing effects of oxytocin treatment in the group receiving placebo during the second 4-week administration period. Subjects not willing to take part in the second trial will exit the study and will be referred to their treating physician.

Eligibility criteria: Inclusion Criteria:

* Medically healthy outpatients between 6 and 12 years of age (cut off 12 years and 11 months)
* Intelligence Quotient \> 40
* Diagnosis of autism spectrum disorder based on the Autism Diagnostic Interview - Revised, Autism Diagnostic Observation Schedule, and DSM-IV criteria
* Clinical Global Impression severity rating of 4 or higher
* Care provider who can reliably bring subject to clinic visits, provide trustworthy ratings, and interacts with the subject on a regular basis
* Stable medications for at least 4 weeks
* No planned changes in psychosocial interventions during the trial
* Willingness to provide blood samples.

Exclusion Criteria:

* Diagnostics and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder
* Regular nasal obstruction or nosebleeds
* Active medical problems: unstable seizures, significant physical illness (e.g., serious liver, renal, or cardiac pathology)
* Sensitivity to preservatives (in particular E 216, E 218, and chlorobutanol hemihydrate)
* A genetic abnormality (e.g., Fragile X Syndrome)
* Significant hearing or vision impairments
* Habitually drinks large volumes of water
* Pregnancy, breastfeeding, or child birth within the last 6 months
* Sexually active females not using a reliable method of contraception.

Primary outcomes:
measure: Change From Baseline in Parent Rated Social Responsiveness Scale (SRS) Scores During Treatment.
timeFrame: Baseline; Week 4
Secondary outcomes:
measure: Number of Participants With Side Effects Assessed Using Parent Rated Dosage Record Treatment Emergent Symptom Scale (DOTES) Scores During Treatment
timeFrame: Baseline through Week 4
measure: Change From Baseline in Height.
timeFrame: Baseline; Week 4
measure: Clinical Global Impression-Improvement (CGI-I) Score at Week 4
timeFrame: Baseline to Week 4
measure: Parent Rated Aberrant Behavior Checklist (ABC) Irritability Scores at Baseline and Week 4
timeFrame: Baseline; Week 4
measure: Change From Baseline in Parent Rated Spence Children's Anxiety Scale (SCAS) During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Vineland Adaptive Behavior Scales, Second Edition - Social and Communication Subscales During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Laboratory Based Facial Emotion Recognition Abilities During Treatment.
timeFrame: Up to 4 weeks
measure: Change From Baseline in Laboratory Based Eye-gaze to Social Cues During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Reading the Mind in the Eyes Test, Child Version (RMET-child) Scores During Treatment.
timeFrame: Up to 4 weeks
measure: Change From Baseline in Laboratory Based Social Mimicry Abilities During Treatment.
timeFrame: Up to 4 weeks
measure: Change From Baseline in Developmental NEuroPSYchological Assessment (NEPSY-II) Affect Recognition Scores During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Plasma Oxytocin Levels During Treatment.
timeFrame: Up to 4 weeks
measure: Change From Baseline in Parent Rated Repetitive Behavior Scale- Revised (RBS-R) Scores During Treatment.
timeFrame: Baseline; Week 4
measure: Change From Baseline in Weight
timeFrame: Baseline; Week 4
measure: Change From Baseline in Heart Rate
timeFrame: Baseline; Week 4
measure: Change From Baseline in Blood Pressure
timeFrame: Baseline; Week 4
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Antonio Y Hardan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Karen J Parker, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Parker KJ, Oztan O, Libove RA, Sumiyoshi RD, Jackson LP, Karhson DS, Summers JE, Hinman KE, Motonaga KS, Phillips JM, Carson DS, Garner JP, Hardan AY. Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism. Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):8119-8124. doi: 10.1073/pnas.1705521114. Epub 2017 Jul 10.