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 Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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:

MedlinePlus related topics: Autism Spectrum Disorder

Drug Information available for: Oxytocin

U.S. FDA Resources

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

Primary Outcome Measures:

Change in ABC-SW subscale--Reciprocal Social Behavior [ Time Frame: Baseline- 2-4-6-8-10-12 -18 months ] [ Designated as safety issue: No ]
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-2-4-6-8-10-12-18 ] [ Designated as safety issue: No ]
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-3-6-9-12-18 months ] [ Designated as safety issue: No ]
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-6-12-18 months ] [ Designated as safety issue: No ]
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-3-6-9-12-18 months ] [ Designated as safety issue: No ]
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-6-12-18 months ] [ Designated as safety issue: No ]
Change in Social Opportunity (Questionaire) [ Time Frame: Baseline-18 months inclusive ] [ Designated as safety issue: No ]
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-2-6-8-12-18 months ] [ Designated as safety issue: Yes ]
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-18 months inclusive ] [ Designated as safety issue: No ]
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-2-6-8-12-18 months ] [ Designated as safety issue: No ]
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-18 months inclusive ] [ Designated as safety issue: No ]
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-18 months inclusive ] [ Designated as safety issue: Yes ]
Systematic elicitation and screening of adverse events will be completed using the SLAES.


Estimated Enrollment:	300
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
Genders Eligible for Study:	Both
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 medications or medication doses of risperidone, aripiprazole, other antipsychotic medications, clonidine, guanfacine, stimulants or anti-convulsants within four weeks of randomization
Subjects who have had previous chronic treatment with oxytocin
Subjects who are currently being treated with an agent that affects brain serotonin levels, including St. John's Wort
Subjects who use benzodiazepines on a regular basis (i.e. 3 of 7 days in a week)
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

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

Contacts


Contact: Lindsey M Hazzard, LCSW	1-800-708-0048	aspire@unc.edu
Contact: Cheryl O Alderman, BS	1-800-708-0048	aspire@unc.edu

Locations


United States, Massachusetts
Lurie Center for Autism, Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Christopher McDougle, MD
United States, New York
Mount Sinai School of Medicine	Recruiting
New York, New York, United States, 10029
Contact: Alexander Kolevzon, MD
Principal Investigator: Alexander Kolevzon, MD
United States, North Carolina
The University of North Carolina at Chapel Hill, Department of Psychiatry	Recruiting
Chapel Hill, North Carolina, United States, 27517
Principal Investigator: Linmarie Sikich, MD
Duke University , Genetics Center	Recruiting
Durham, North Carolina, United States, 27710
Principal Investigator: Simon Gregory, PhD
United States, Tennessee
Vanderbilt University	Recruiting
Nashville, Tennessee, United States, 37212
Sub-Investigator: Jeremy Veenstra-VanderWeele, MD, PhD
Sub-Investigator: Zachary Warren, PhD
United States, Washington
Seattle Children's Hospital Research Institute	Recruiting
Seattle, Washington, United States, 98105
Principal Investigator: Bryan King, MD

Sponsors and Collaborators

University of North Carolina, Chapel Hill

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

Investigators


Principal Investigator:	Linmarie Sikich, MD	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:	NCT01944046 History of Changes
Other Study ID Numbers:	13-0593, 1U01HD073984
Study First Received:	June 13, 2013
Last Updated:	August 12, 2014
Health Authority:	United States: Federal Government United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:


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

Additional relevant MeSH terms:


Oxytocin Oxytocics Pharmacologic Actions	Physiological Effects of Drugs Reproductive Control Agents Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015

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