Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Intranasal Oxytocin Treatment for Social Deficits in Children With Autism

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Stanford University
Sponsor:
Information provided by (Responsible Party):
Stanford University
ClinicalTrials.gov Identifier:
NCT01624194
First received: June 18, 2012
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Autism
Drug: Oxytocin nasal spray
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-blind, Randomized, Placebo Controlled Trial of Intranasal Oxytocin Treatment for Social Deficits in Children With Autism.

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Change from baseline in parent rated Social Responsiveness Scale (SRS) scores during treatment. [ Time Frame: 4-weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Parent rated Dosage Record Treatment Emergent Symptom Scale (DOTES) scores during treatment. [ Time Frame: Single-dose, 4-week, 8-week ] [ Designated as safety issue: Yes ]
  • Change from baseline in heart rate, blood pressure, body temperature, and body mass index. [ Time Frame: Single-dose, 4-week, 8-week ] [ Designated as safety issue: Yes ]
  • Change from baseline in Clinical Global Impression (CGI) scores during treatment. [ Time Frame: 4-week, 8-week ] [ Designated as safety issue: Yes ]
  • Change from baseline in parent rated Social Responsiveness Scale (SRS) scores during treatment. [ Time Frame: 8-week ] [ Designated as safety issue: No ]
  • Change from baseline in parent rated Aberrant Behavior Checklist (ABC) scores during treatment. [ Time Frame: 4-week, 8-week ] [ Designated as safety issue: No ]
  • Change from baseline in parent rated Spence Children's Anxiety Scale (SCAS) during treatment. [ Time Frame: 4-week, 8-week ] [ Designated as safety issue: No ]
  • Change from baseline in Vineland Adaptive Behavior Scales - Social and Communication subscales during treatment. [ Time Frame: 4-weeks, 8-weeks ] [ Designated as safety issue: No ]
  • Change from baseline in laboratory based facial emotion recognition abilities during treatment. [ Time Frame: Single-dose, 4-week, 8-week ] [ Designated as safety issue: No ]
  • Change from baseline in laboratory based eye-gaze to social cues during treatment. [ Time Frame: Single-dose, 4-week, 8-week ] [ Designated as safety issue: No ]
  • Change from baseline in Reading the Mind in the Eyes Test, child version (RMET-child) scores during treatment. [ Time Frame: Single-dose, 4-week, 8-week ] [ Designated as safety issue: No ]
  • Change from baseline in laboratory based social mimicry abilities during treatment. [ Time Frame: Single-dose, 4-week, 8-week ] [ Designated as safety issue: No ]
  • Change from baseline in NEPSY-II (Social Perception and Memory for Faces & Names subscales) scores during treatment. [ Time Frame: Single-dose, 4-week, 8-week ] [ Designated as safety issue: No ]
  • Change from baseline in plasma oxytocin, vasopressin, and cortisol levels during treatment. [ Time Frame: 4-week, 8-week ] [ Designated as safety issue: No ]
  • Change from baseline in parent rated Repetitive Behavior Scale Revised (RBS-R) scores during treatment. [ Time Frame: 4-week, 8-week ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: June 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: Oxytocin nasal spray
24IU BID (3 x 0.1 mL [4IU] sprays per nostril twice daily for 4-weeks.
Other Name: Syntocinon® Nasal Spray
Placebo Comparator: 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.
Drug: Placebo
3 x 0.1 mL sprays per nostril twice daily for 4-weeks.

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

Ages Eligible for Study:   6 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01624194

Contacts
Contact: Robin Libove, BS (650) 736-1235 rlibove@stanford.edu
Contact: Dean S Carson, PhD (650) 736-1235 dcarson@stanford.edu

Locations
United States, California
Stanford University School of Medicine Recruiting
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Antonio Y Hardan, MD Stanford University
Principal Investigator: Karen J Parker, PhD Stanford University
Study Director: Dean S Carson, PhD Stanford University
  More Information

No publications provided

Responsible Party: Stanford University
ClinicalTrials.gov Identifier: NCT01624194     History of Changes
Other Study ID Numbers: SU-12132011-8827
Study First Received: June 18, 2012
Last Updated: June 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Autistic Disorder
Child Development Disorders, Pervasive
Mental Disorders
Mental Disorders Diagnosed in Childhood
Oxytocin
Oxytocics
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014