A Study of Oxytocin in Children and Adolescents With Autistic Disorder (Oxytocin)
|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|
- 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.
- 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.
|Study Start Date:||March 2011|
|Study Completion Date:||April 2013|
|Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Intervention: Drug: placebo
Placebo Nasal Spray
Active Comparator: Oxytocin
Intervention: Drug: Syntocinon® Nasal Spray
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01308749
|United States, North Carolina|
|University of North Carolina Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599|
|Principal Investigator:||Linmarie Sikich, M.D.||University of North Carolina, Chapel Hill|