A Study of Oxytocin in Children and Adolescents With Autistic Disorder

This study has been completed.
Sponsor:
Collaborator:
Autism Speaks
Information provided by (Responsible Party):
Linmarie Sikich, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01308749
First received: February 28, 2011
Last updated: September 10, 2013
Last verified: September 2013
  Purpose

The investigators propose to conduct this pilot study to evaluate oxytocin as a supplemental treatment for improving social difficulties in individuals with autism.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Pilot Study of Oxytocin in Children and Adolescents With Autistic Disorder

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Tolerability [ Time Frame: Over 16 weeks double blind and open treatment phase ] [ Designated as safety issue: Yes ]
    This study will help to determine tolerability of intranasal oxytocin treatment in children with autism by measuring the ability of at least 80% of the sample to tolerate twice daily intranasal administration of oxytocin.


Secondary Outcome Measures:
  • Biomarkers [ Time Frame: During 3 time points in the study: (1) Screening or Baseline, (2) Week 8, and (3) Week 16 ] [ Designated as safety issue: No ]
    Blood samples will be collected to obtain proof of concept data regarding the potential utility of OTX mRNA expression, OTXR methylation and OTXR mRNA expression as biomarkers for social disabilities in autism or oxytocin treatment response.

  • Adverse effects of Oxytocin Nasal Spray [ Time Frame: During the 16 week, blinded and open treatment phases ] [ Designated as safety issue: Yes ]
    The study will examine the incidence and severity of systematically elicited adverse events and abnormal labs, vitals signs, and electrocardiographic abnormalities.

  • Satisfaction [ Time Frame: 16 weeks, 8 wks blinded & 8 wks ope ] [ Designated as safety issue: No ]
    Caregivers (and participants when developmentally appropriate) will complete ratings of satisfaction with the treatment at the end of each treatment phase

  • Social reciprocity [ Time Frame: 8 weeks, blinded treatment ] [ Designated as safety issue: No ]
    The SRS will be used to assess social interest and skills

  • ADOS Severity Score [ Time Frame: Baseline to 16 Weeks ] [ Designated as safety issue: No ]

    The Autism Diagnostic Observation Schedule (ADOS) is a semi-structured assessment used to assess and diagnose individuals suspected of having autism of varying ages, developmental levels, and language skills (from no speech to verbally fluent). The ADOS includes four modules, each requiring just 35-40 minutes to administer. The individual being evaluated is given just one module, depending on his or her expressive language level and chronological age. The rater will observe social and communication behaviors during various activities in the appropriate module.

    We will graphically examine the relationship between baseline levels of the biomarker measures and the within-subject change for severity at each of the major time points during oxytocin treatment and placebo treatment.


  • ABC-Social Withdrawal [ Time Frame: Baseline to 16 Weeks ] [ Designated as safety issue: No ]

    The Aberrant Behavior Checklist (ABC) focuses on problem behaviors in five sub-domains: irritability, attention, repetitive behaviors, unusual speech, and social withdrawal.

    We will graphically examine the relationship between the ABC-Social Withdrawal sub-domain and baseline levels of the biomarker measures at each of the major time points during oxytocin treatment and placebo treatment.


  • Pervasive Developmental Disorder Behavior Inventory (PDD-BI) [ Time Frame: Baseline to 16 Weeks ] [ Designated as safety issue: No ]

    The PDD-BI examines both adaptive and maladaptive behaviors related to autism. It has normative scores for children between 2-11 years. For children 12 years and older, the norms (11 years, 11 months) will be used.

    We will graphically examine the relationship between the PDD-BI outcome measure and the baseline levels of the biomarker measures at each of the major time points during oxytocin treatment and placebo treatment.



Enrollment: 25
Study Start Date: March 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Intervention: Drug: placebo
Drug: Placebo
Placebo Nasal Spray
Other Name: Placebo
Active Comparator: Oxytocin
Intervention: Drug: Syntocinon® Nasal Spray
Drug: Oxytocin

Subjects will use the Syntocinon® Nasal Spray (oxytocin) twice daily for 8 weeks if they are randomized to that arm in the Randomized Phase. All subjects will use the Syntocinon® Nasal Spray twice daily for 8 weeks in the Open Label Phase.

Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU.

Other Name: Syntocinon® Nasal Spray

Detailed Description:

The proposed pilot study is an essential first step toward rigorously evaluating oxytocin treatment of individuals with autism. The biologic actions of oxytocin on social cognition and prosocial behaviors and the clinical, genetic and epigenetic evidence for involvement of the oxytocin system in the pathophysiology of some cases of autism strongly suggest that supplemental oxytocin therapy could significantly improve the social disabilities involved in autism. Many people feel that these social difficulties are the most characteristic and central feature of autism. Overall, this study aims to determine the tolerability, accessibility, and feasibility of an oxytocin pilot study.

This study will consent up to 30 subjects in order to randomize up to 25 subjects into a 2-month (8 weeks) randomized double-blind, placebo-controlled initial treatment period, a subsequent 2-month (8 weeks) period in which all participants receive oxytocin, and up to three post-treatment visits that occur at week 28 (±2 weeks),an interim visit anytime between week 16 and week 76 only for those patients who plan to start oxytocin on their own outside of study treatment and who will experience a lag time between week 16 (end of open label treatment) and when outside oxytocin treatment will begin, and some time before week 76. The investigators hope that this study will help to inform future study designs in determining whether a short term or long term treatment trial is necessary to observe significant effects. This will also help to develop systematic preliminary safety measures.

  Eligibility

Ages Eligible for Study:   3 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Between 3 and 17 years old, inclusive.
  • Have a clinical diagnosis of autistic disorder confirmed according to DSM-IV criteria by using the Autism Diagnostic Interview - Revised (ADI-R) and/or the Autism Diagnostic Observation Scale (ADOS, Lord et al., 1989).

Exclusion Criteria:

  • Changes in allied health therapies, behavioral or educational interventions within the past 2 months of the baseline visit other than those associated with school holidays.
  • Changes in psychotropic and alternative medication doses in the last 30 days of the baseline visit.
  • Subjects with a medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. This includes, but is not limited to, Rett Syndrome, impairment of renal function, evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder and uncontrolled hypertension), respiratory, hepatic, or gastrointestinal disease.
  • Marked sensory impairment such as deafness or blindness that would interfere with conduct of the study.
  • Pregnancy/Nursing because of the unknown effects of oxytocin to unborn babies and/or nursing infants. All females of child-bearing potential will be administered a urine or serum pregnancy test at screening and at any point during the study at physician discretion. Refusal to undergo a pregnancy test will result in exclusion from the study. The investigators will share results of pregnancy test with the subject's legal guardian.
  • Refusal to practice contraception if sexually active because the effects of exposure to high concentrations of oxytocin on sperm or newly conceived embryos are unknown. Sexually active men and women should not take part in this study if they and their partners are not both using an effective birth control method (for example, women use birth control pills, an intrauterine device [IUD] or a diaphragm and men use condoms).
  • Inability of caretakers to speak English.
  • Absence of a consistent caretaker to report on symptoms.
  • Subjects who, in the Investigator's opinion, might not be suitable for the study.
  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: NCT01308749

Locations
United States, North Carolina
University of North Carolina Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Autism Speaks
Investigators
Principal Investigator: Linmarie Sikich, M.D. University of North Carolina, Chapel Hill
  More Information

No publications provided

Responsible Party: Linmarie Sikich, MD, Associate Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01308749     History of Changes
Other Study ID Numbers: 11-0493
Study First Received: February 28, 2011
Last Updated: September 10, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on September 18, 2014