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

Phase II Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors

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.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorders
• Intervention / Treatment: Drug: Double blind phase Placebo Nasal Spray; Drug: double Blind Oxytocin Nasal Spray; Drug: Open Label 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.

• Study Type: Interventional
• Enrollment (Actual): 290
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: DB Placebo Nasal Spray; Placebo treatment during weeks 0-24 double blind phase	Drug: Double blind phase Placebo Nasal Spray; This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except oxytocin will NOT be added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.; Other Names: DB Placebo (PL)
Active Comparator: DB Oxytocin Nasal Spray; DB Oxytocin- quadruply masked treatment with intranasal oxytocin during weeks 0-24 of study during double blind phase of study	Drug: double Blind 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 weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.; Other Names: DB Intranasal Oxytocin (OT)
Active Comparator: 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	Drug: Open Label intranasal oxytocin; All participants who completed the 24 week double blind phase were eligible to join a 24 week open label phase in which all participants received intranasal oxytocin; Other Names: open label treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity	The primary outcome is Change in Aberrant Behavior Checklist-Modified Social Withdrawal subscale- a measure of reciprocal social behaviors. ABC-mSW is a modification of the ABC-Lethargy subscale. The ABC-mSW consists of the sum of questions 5,12,16, 20, 23, 26, 30, 37, 40, 42, 43, 55, and 58. In contrast to the ABC-Lethargy subscale it eliminates question 3 (listless, sluggish, inactive), question 32 (sits or stands in one position for a long time), and question 53 (inactive, never moves spontaneously). Thirteen individual items are scored 0-3, therefore the range is 0-39. Higher score indicates lower social reciprocity. Repeated measures were obtained at baseline, weeks 4, 8, 12, 16, 20, 24.	Least Mean Squares Double-blind phase: change from baseline to week 24
Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity	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.	Least mean squares for Open Label: Change between weeks 24-48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Sociability Factor (SF)	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.	Double-blind phase: change in least means squares between week 0 & 24.
Change in Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score	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.	Double-blind phase: baseline, weeks 12, 24
Change in Stanford Binet-5th Edition (SB-5) IQ Score	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.	Double-blind phase: baseline to week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score	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.	Open Label: weeks 24, 48
Change in Vineland II Adaptive Behavior Scales (VABS-II) Daily Living Domain Score	Functional skills will be assessed using the VABS-II Daily Living Domain Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement.	Double-blind phase: baseline, week 24; Open Label: week 48
Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Mean Score	Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. Each item on the subjective internalizing CSQ subscale is rated from 1 to 5. Then all items within the subscale are summed and the mean is determined based on the number of items in the subscale. Higher score indicates more caregiver strain. Lower value in change indicates more improvement.	Open Label: weeks 24, 48
Change in Vineland II Adaptive Behavior Scales (VABS-II) Communication Domain Score	Functional skills will be assessed using the VABS-II Communication Domain Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement.	Double-blind phase: baseline, week 24; Open Label: week 48
Change in Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Score	Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. CSQ subscale scores are ranged from 1 to 5. with each item of the subscale having the same range, the sum of the items within the subscale are summed, and the mean score is determined (I.e. a single # between 1 and 5) and reported. Higher scores indicate more caregiver strain. Lower value in change indicates more improvement.	Double-blind phase: baseline, week 24
Change in Vineland II Adaptive Behavior Scales (VABS-II) Socialization Domain Score	Functional skills will be assessed using the VABS-II Socialization Domain Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement.	Double-blind phase: baseline, week 24; Open Label: week 48
Change in Caregiver Strain Questionnaire (CSQ) Objective Subscale Score	Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. CSQ subscale scores are ranged from 1 to 5. Higher score indicates more caregiver strain. Lower value in change indicates more improvement. The analysis directions for the instrument that are used in these analyses are the mean of all the responses in the scale or subscale.	Double-blind phase: baseline, week 24; Open Label: week 48
Change in Caregiver Strain Questionnaire (CSQ) Subjective Externalizing Subscale Score	Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. CSQ subscale scores are ranged from 1 to 5. Higher score indicates more caregiver strain. Lower value in change indicates more improvement.	Double-blind phase: baseline, week 24; Open Label: week 48
Change in Vineland II Adaptive Behavior Scales (VABS-II) Composite Score	Functional skills including communication will be assessed using the VABS-II Adaptive Behavior Composite Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement.	Double-blind phase: baseline, week 24
Change in Clinical Global Impressions -Improvement Score (CGI-I)	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. scores of 1 and 2 are considered as a percentage of total subjects in arm	Double blind phase: change from Baseline to week 12, and week 24. Open label phase change from week 24 to week 48
Reading Mind in the Eyes Test is an Objective Measures of the Extent to Which Verbal Participants With Rudimentary Knowledge of Emotion Names Are Able to Correctly Identify the Emotion Shown in a Black and White Picture of the Eyes and Nose of an Actor.	This computerized task consists of a series of pictures of eyes in which the participant needs to determine which emotion the eyes are expressing from 4 emotions listed along with the picture. The outcome is the % of pictures with correct emotion identified. The range is 0 to 100%. The larger percent identified correctly indicates better ability to perceive emotions. An increase or positive change indicates better ability to identify emotions since baseline.	Double blind phase: change from Baseline and week 24. Note: only those who demonstrated understanding of these concepts were included in sample.

Collaborators and Investigators

• Sponsor: Linmarie Sikich
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Linmarie Sikich, MD, Duke University

Publications and helpful links

General Publications

• Spanos M, Chandrasekhar T, Kim SJ, Hamer RM, King BH, McDougle CJ, Sanders KB, Gregory SG, Kolevzon A, Veenstra-VanderWeele J, Sikich L. Rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B). Contemp Clin Trials. 2020 Nov;98:106103. doi: 10.1016/j.cct.2020.106103. Epub 2020 Aug 8.
• Sikich L, Kolevzon A, King BH, McDougle CJ, Sanders KB, Kim SJ, Spanos M, Chandrasekhar T, Trelles MDP, Rockhill CM, Palumbo ML, Witters Cundiff A, Montgomery A, Siper P, Minjarez M, Nowinski LA, Marler S, Shuffrey LC, Alderman C, Weissman J, Zappone B, Mullett JE, Crosson H, Hong N, Siecinski SK, Giamberardino SN, Luo S, She L, Bhapkar M, Dean R, Scheer A, Johnson JL, Gregory SG, Veenstra-VanderWeele J. Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder. N Engl J Med. 2021 Oct 14;385(16):1462-1473. doi: 10.1056/NEJMoa2103583.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): November 30, 2017
• Study Completion (Actual): November 30, 2017

Study Registration Dates

• First Submitted: June 13, 2013
• First Submitted That Met QC Criteria: September 12, 2013
• First Posted (Estimate): September 17, 2013

Study Record Updates

• Last Update Posted (Actual): June 18, 2021
• Last Update Submitted That Met QC Criteria: May 27, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: autism, ASD, autistic, Asperger's, PDD-NOS, oxytocin
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autistic Disorder; Autism Spectrum Disorder; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: Pro00063950; 1U01HD073984 (U.S. NIH Grant/Contract); 13-0593 (Other Identifier: UNC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Most data will be available on NDAR, but will not be identifiable.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No