Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors - Full Text View

Purpose

The purpose of this research study is to learn about the effects of intranasal oxytocin as a supplemental 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.

Condition	Intervention	Phase
Autism Spectrum Disorders	Drug: Placebo Nasal Spray Drug: Oxytocin Nasal Spray	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Phase II Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors

Resource links provided by NLM:

Drug Information available for: Oxytocin

U.S. FDA Resources

Further study details as provided by Linmarie Sikich, Duke University Medical Center:

Primary Outcome Measures:

Change in ABC-SW subscale--Reciprocal Social Behavior [ Time Frame: Baseline- 2-4-6-8-10-12 months ]
The primary outcome is reciprocal social behaviors, which will be assessed using two co-primary measures. The first measure is the ABC-SW subscale, which is being used in other clinical trials focusing on the core social and communication symptoms of autism.
Change in Sociability Factor (SF) [ Time Frame: Baseline-2-4-6-8-10-12 ]
The other primary measure is the Sociability Factor (SF), a combined measure derived from 13 items of the ABC-SW, which primarily captures aloof, and avoidant behaviors, and the Pervasive Developmental Disorders Behavior Inventory-Screening Version (PDDBI-SV).

Secondary Outcome Measures:

Change in SRS-Social Motivation Subscale [ Time Frame: Baseline-3-6-9-12 months ]
Social Responsiveness Scale (SRS)-Social Motivation subscale, was developed to provide a quantitative measure of social impairments typically observed in ASD in children 3-18 years.
Change in Stanford Binet-5th Edition (SB-5)/Mullen [ Time Frame: Baseline-6 months ]
Cognitive skills will be assessed using the Stanford Binet-5th Edition (SB-5) (Roid). If a participant cannot complete the routing tests on the SB-5, they will be assessed using the Mullen.
Change in Vineland II Adaptive Behavior Composite and all its subscales [ Time Frame: Baseline-3-6-9-12 months ]
Functional skills including communication will be assessed using the standard score of the Vineland 2 adaptive behavior composite and all its subscales.
Change in Caregiver Strain Questionnaire total and subscale scores [ Time Frame: Baseline-6-12 months ]
Change in Social Opportunity (Questionaire) [ Time Frame: Baseline-12 months inclusive ]
This UNC created form asks parents to rate how frequently their child has the opportunity to interact with different individuals in the community, home, school and daycare/after-school setting. It also asks, of those opportunities that their child has, does their child actually utilize those opportunities to interact with individuals in a social manner.

Other Outcome Measures:

Changes in Biologic Outcome Measures [ Time Frame: Baseline-2-6-8-12 months ]
Investigators will obtain blood, urine and vital signs from participants at regular intervals in order to assess the safety of oxytocin. In addition,the blood samples will also be used to assess oxytocin levels, OTXR differential methylation status and to assess mRNA expression. Investigators will obtain saliva at the same time points to perform salivary oxytocin levels.
Change in CGI-S and analysis in improvement score (CGI-I) [ Time Frame: Baseline-12 months inclusive ]
The Clinical Global Impressions - Improvement score and Severity score, which is routinely used in pharmacologic clinical trials, will capture the study physician's global impression of response.
Reading Mind in the Eyes Test (change from baseline and/or previous month) [ Time Frame: Baseline-2-6-8-12 months ]
This computerized task consists of a series of pictures of eyes in which the participant needs to determine which emotion the eyes are expressing.
Change in CASI from previous month [ Time Frame: Baseline-12 months inclusive ]
Childhood Anxiety Sensitivity Index (CASI): This scale is designed for measuring anxiety sensitivity (i.e., the belief that anxiety symptoms have negative consequence
Change in Systematic Longitudinal Adverse Events Scale (SLAES) [ Time Frame: Baseline-12 months inclusive ]
Systematic elicitation and screening of adverse events will be completed using the SLAES.


Enrollment:	290
Study Start Date:	August 2014
Estimated Study Completion Date:	October 2017
Estimated Primary Completion Date:	October 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo Nasal Spray Placebo	Drug: Placebo Nasal Spray Other Name: Placebo
Active Comparator: Oxytocin Nasal Spray Oxytocin	Drug: Oxytocin Nasal Spray Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and months 1 and 2 until achieving the target dose of 24 IU BID at Month 2. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved. Other Name: Intranasal Oxytocin

Arms

Assigned Interventions

Placebo Comparator: Placebo Nasal Spray

Placebo

Drug: Placebo Nasal Spray

Other Name: Placebo

Active Comparator: Oxytocin Nasal Spray

Oxytocin

Drug: Oxytocin Nasal Spray

Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and months 1 and 2 until achieving the target dose of 24 IU BID at Month 2. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.

Other Name: Intranasal Oxytocin

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.

Eligibility


Ages Eligible for Study:	3 Years to 17 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

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: NCT01944046

Locations


United States, Massachusetts
Lurie Center for Autism, Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
Center for Autism and the Developing Brain
White Plains, New York, United States, 10605
United States, North Carolina
The University of North Carolina at Chapel Hill, Department of Psychiatry
Chapel Hill, North Carolina, United States, 27517
Duke Center for Autism and Brain Development
Durham, North Carolina, United States, 27705
Duke University , Genetics Center
Durham, North Carolina, United States, 27710
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37212
United States, Washington
Seattle Children's Hospital Research Institute
Seattle, Washington, United States, 98105

Sponsors and Collaborators

Linmarie Sikich

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators


Principal Investigator:	Linmarie Sikich, MD	Duke University

More Information


Responsible Party:	Linmarie Sikich, Associate Professor, Duke University Medical Center
ClinicalTrials.gov Identifier:	NCT01944046 History of Changes
Other Study ID Numbers:	Pro00063950 1U01HD073984 ( US NIH Grant/Contract Award Number ) 13-0593 ( Other Identifier: UNC )
Study First Received:	June 13, 2013
Last Updated:	January 3, 2017

Keywords provided by Linmarie Sikich, Duke University Medical Center:


autism, ASD, autistic, Asperger's, PDD-NOS, oxytocin

Additional relevant MeSH terms:


Autistic Disorder Autism Spectrum Disorder Child Development Disorders, Pervasive Neurodevelopmental Disorders Mental Disorders	Oxytocin Oxytocics Reproductive Control Agents Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 28, 2017

Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors (SOARS-B)