Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors

Phase 2

Completed

Conditions: Autism Spectrum Disorders

Interventions: Drug: Open Label intranasal oxytocin
Drug: Double blind phase Placebo Nasal Spray
Drug: double Blind Oxytocin Nasal Spray

Registration Number: NCT01944046

Lead Sponsor: Linmarie Sikich

Brief Summary: The purpose of this research study is to learn about the effects of supplemental intranasal oxytocin as a treatment for improving social difficulties in children and adolescents with autism. This study will also provide additional information about the safety and tolerability of intranasal oxytocin. Investigators expect oxytocin will increase social motivation, improving daily living skills and quality of life.

Detailed Description: There is a tremendous unmet need for accessible treatments that address core symptoms of ASD and are safe for sustained use. The Study of Oxytocin in ASD to improve Reciprocal Social Behaviors or (SOARS-B) will test a very promising potential treatment-intranasal oxytocin-for ASD's fundamental social communication deficits in a large, group of verbal and nonverbal children. SOARS-B will also provide information about the regulation of DNA methylation and transcription of the oxytocin receptor gene (OXTR), as well as other genes relevant to oxytocin's CNS activity, as a function of time and in response to oxytocin treatment. These data will fill a key gap in our understanding of oxytocin's role in ASD and its ability to alter epigenetic modifications of the OXTR.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 290

Inclusion Criteria

Be between the ages of 3 years 0 months and 17 years 11 months at the time of randomization
Be diagnosed by clinician experienced in assessment of ASD with autistic disorder, Asperger's syndrome, or PDD-NOS using DSM-V-TR criteria
Must have clinical diagnosis of ASD confirmed using the Autism Diagnostic Observation Scale (ADOS, Lord et al., 2001)
Must have clinical diagnosis of ASD confirmed using the Autism Diagnostic Interview-Revised (ADI-R, Rutter, 2003). ASD criteria proposed by Risi (2006). Specifically, subject must be within 1 point of autism criteria on both social and communication domains of the ADI or meet autism criteria in one of these ADI domains and come within 2 points of autism criteria in the other
Have a guardian who is able to provide informed consent
If cognitively able, subject must be able to provide informed assent/consent

Exclusion Criteria

Have a known diagnosis of Rett Syndrome or Childhood Disintegrative Disorder, or have marked sensory impairment such as deafness or blindness
Have active cardiovascular disease or renal disease that is not controlled by medication
Subjects who are pregnant, lactating, or who refuse to practice contraception if sexually active
Subjects who have had changes in allied health therapies, behavioral or educational interventions within the two months prior to randomization other than those associated with school holidays
Subjects who have had changes in psychiatric medications within 4 weeks of randomization
Subjects who have had previous chronic treatment with oxytocin
Subjects who have caretakers who are unable to speak English, be consistently present at visits to report on symptoms, or are otherwise judged as unable to comply with the protocol by the data collection site team
Subjects with active seizures within the 6 months preceding screening or baseline -added part way through study in response to subject death.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
open label intranasal oxytocin	Open Label intranasal oxytocin	non masked treatment with intranasal oxytocin from weeks 24-48 in those participants who completed first 24 weeks of double blind treatment
DB Placebo Nasal Spray	Double blind phase Placebo Nasal Spray	Placebo treatment during weeks 0-24 double blind phase
DB Oxytocin Nasal Spray	double Blind Oxytocin Nasal Spray	DB Oxytocin- quadruply masked treatment with intranasal oxytocin during weeks 0-24 of study during double blind phase of study

Primary Outcome Measures

Name	Time	Method
Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity	Least mean squares for Open Label: Change between weeks 24-48	The ABC-mSW is described above and involves 13 items reflecting lack of reciprocal interaction. Each item is scored from 0 (never shows behavior) to 3 (behavior is a major problem). The range is 0-39. Higher scores indicate worse reciprocal social functioning.

Secondary Outcome Measures

Name	Time	Method
Change in Sociability Factor (SF)	Double-blind phase: change in least means squares between week 0 & 24.	The Sociability Factor (SF) is a summed measure of the13 items of the ABC-SW and the 18 items of the Pervasive Development Disorders Behavior Inventory-Screening Version (PDDBI-SV).The PDDBI-SV assesses both adaptive social behaviors and social problems typical of ASD. The adaptive behaviors are reverse scored so that all the analyzed scores range from 0-performing in a neurotypical fashion to 3 typically performs in a way associated with ASD. the total # of items on this summed measure is 31 with a range from 0 to 93. More impaired social functioning indicated by higher scores. This measure was changed to a secondary outcome in the final statistical analysis plan.
Change in Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score	Double-blind phase: baseline, weeks 12, 24	The SRS-Social Motivation subscale was developed to provide a quantitative measure of social impairments typically observed in ASD in children 3-18 years. Reported as T-score with a range of 38-90 for both boys and girls. Higher score indicates more severe clinical condition. Lower value in change indicates more improvement.
Change in Stanford Binet-5th Edition (SB-5) IQ Score	Double-blind phase: baseline to week 24	Cognitive skills will be assessed using the Stanford Binet-5th Edition (SB-5) (Roid). Acceptable IQ range is 47-153, with higher score being better. Higher change scores indicate more improvement.

Trial Locations

Locations (7): Lurie Center for Autism, Massachusetts General Hospital
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Boston, Massachusetts, United States
Duke Center for Autism and Brain Development
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Durham, North Carolina, United States
Duke University , Genetics Center
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Durham, North Carolina, United States
Center for Autism and the Developing Brain
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White Plains, New York, United States
Mount Sinai School of Medicine
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New York, New York, United States
Seattle Children's Hospital Research Institute
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Seattle, Washington, United States
Vanderbilt University
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Nashville, Tennessee, United States