Intranasal Oxytocin Treatment for Social Deficits in Children With Autism

NCT ID: NCT01624194

Last Updated: 2019-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2016-05-31

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.

Conditions

Autism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Oxytocin nasal spray

Prior to randomization, all subjects will participate in a 1-week open-label placebo lead-in trial. Each subject will be administered the placebo nasal spray at Stanford University and then their parent will continue administering the nasal spray to the subject for 1 week at home. Each subject will then be randomly assigned either to the active group or to the placebo (stratified by gender) and will be given the appropriate nasal spray bottle and their parents will be responsible for administering 3 puffs per nostril (4 IU/puff) to their child for a total dose of 24 IU oxytocin or placebo twice daily (BID; morning and evening) for 4-weeks. On completion of this 4-week treatment trial subjects will have the option of participating in a second double-blind trial in which they will be assigned to the alternate nasal spray, to that which they received during the first 4-week trial, for an additional 4-week period.

Group Type: ACTIVE_COMPARATOR

Oxytocin nasal spray

Intervention Type: DRUG

24IU BID (3 x 0.1 mL \[4IU\] sprays per nostril twice daily for 4-weeks.

Placebo nasal spray

The placebo nasal spray bottles will be prepared by adding all of the ingredients used in the Syntocinon nasal sprays with the exception of the concentrated oxytocin solution.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

3 x 0.1 mL sprays per nostril twice daily for 4-weeks.

Interventions

Oxytocin nasal spray

24IU BID (3 x 0.1 mL \[4IU\] sprays per nostril twice daily for 4-weeks.

Intervention Type: DRUG

Placebo

3 x 0.1 mL sprays per nostril twice daily for 4-weeks.

Intervention Type: DRUG

Other Intervention Names

Syntocinon® Nasal Spray

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Antonio Hardan

Associate Professor of Child Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Antonio Y Hardan, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Karen J Parker, PhD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 28696286 (View on PubMed)

Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.

Reference Type: DERIVED

PMID: 37811711 (View on PubMed)

Other Identifiers

SU-12132011-8827

Identifier Type: -

Identifier Source: org_study_id