Intranasal Oxytocin Treatment for Social Deficits in Children With Autism

NCT01624194 | Completed Phase 2 Results DMC

• 1 other identifier: SU-12132011-8827
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Autism

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Parent Rated Social Responsiveness Scale (SRS) Scores During Treatment.

  Social Responsiveness Scale (SRS) raw scores measure social abilities with lower raw scores meaning better social abilities. (Raw Score Range: 0 - 195)

  Baseline; Week 4

Secondary Outcomes (16)

• Number of Participants With Side Effects Assessed Using Parent Rated Dosage Record Treatment Emergent Symptom Scale (DOTES) Scores During Treatment

  Baseline through Week 4

• Change From Baseline in Height.

  Baseline; Week 4

• Clinical Global Impression-Improvement (CGI-I) Score at Week 4

  Baseline to Week 4

• Parent Rated Aberrant Behavior Checklist (ABC) Irritability Scores at Baseline and Week 4

  Baseline; Week 4

• Change From Baseline in Parent Rated Spence Children's Anxiety Scale (SCAS) During Treatment.

  Baseline; Week 4

Study Arms (2)

Oxytocin nasal spray

ACTIVE COMPARATOR

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.

Drug: Oxytocin nasal spray

Placebo nasal spray

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Oxytocin nasal spray DRUG

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

Also known as: Syntocinon® Nasal Spray

Oxytocin nasal spray

Placebo DRUG

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

Placebo nasal spray

Eligibility Criteria

• Age: 6 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (2)

• 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.

  PMID: 28696286 RESULT

• 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.

  PMID: 37811711 DERIVED

MeSH Terms

Conditions

Autistic Disorder

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Limitations and Caveats

The final sample was 84% male and was not powered to detect sex differences in treatment response. Participants were permitted to take other medications during the intervention. Many of our outcome measures relied on parent report.

Results Point of Contact

• Title: Antonio Y. Hardan, MD
• Organization: Stanford University

hardanay@stanford.edu

(650) 736-1235

Study Officials

• Antonio Y Hardan, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Karen J Parker, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Child Psychiatry

Study Record Dates

• First Submitted: June 18, 2012
• First Posted: June 20, 2012
• Study Start: June 1, 2012
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: July 15, 2019
• Results First Posted: June 6, 2018

Record last verified: 2019-07

Locations

US (1)