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

Primary Purpose

Autism Spectrum Disorders

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Double blind phase Placebo Nasal Spray

double Blind Oxytocin Nasal Spray

Open Label intranasal oxytocin

About this trial

This is an interventional treatment trial for Autism Spectrum Disorders focused on measuring autism, ASD, autistic, Asperger's, PDD-NOS, oxytocin

Eligibility Criteria

3 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Lurie Center for Autism, Massachusetts General Hospital
Mount Sinai School of Medicine
Center for Autism and the Developing Brain
Duke Center for Autism and Brain Development
Duke University , Genetics Center
Vanderbilt University
Seattle Children's Hospital Research Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Arm Label

DB Placebo Nasal Spray

DB Oxytocin Nasal Spray

open label intranasal oxytocin

Arm Description

Placebo treatment during weeks 0-24 double blind phase

DB Oxytocin- quadruply masked treatment with intranasal oxytocin during weeks 0-24 of study during double blind phase of study

non masked treatment with intranasal oxytocin from weeks 24-48 in those participants who completed first 24 weeks of double blind treatment

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

Full Information

NCT ID

NCT01944046

First Posted

June 13, 2013

Last Updated

May 27, 2021

Sponsor

Linmarie Sikich

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT01944046

Brief Title

Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors

Acronym

SOARS-B

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Completed

Study Start Date

August 1, 2014 (Actual)

Primary Completion Date

November 30, 2017 (Actual)

Study Completion Date

November 30, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Linmarie Sikich

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autism Spectrum Disorders

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Randomized, Double-blind, placebo-controlled clinical trial for 24 weeks. Followed by 24 week open label treatment period in which ALL participants receive Oxytocin

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Quadruple

Allocation

Randomized

Enrollment

290 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DB Placebo Nasal Spray

Arm Type

Placebo Comparator

Arm Description

Placebo treatment during weeks 0-24 double blind phase

Arm Title

DB Oxytocin Nasal Spray

Arm Type

Active Comparator

Arm Description

DB Oxytocin- quadruply masked treatment with intranasal oxytocin during weeks 0-24 of study during double blind phase of study

Arm Title

open label intranasal oxytocin

Arm Type

Active Comparator

Arm Description

non masked treatment with intranasal oxytocin from weeks 24-48 in those participants who completed first 24 weeks of double blind treatment

Intervention Type

Drug

Intervention Name(s)

Double blind phase Placebo Nasal Spray

Other Intervention Name(s)

DB Placebo (PL)

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

double Blind Oxytocin Nasal Spray

Other Intervention Name(s)

DB Intranasal Oxytocin (OT)

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Open Label intranasal oxytocin

Other Intervention Name(s)

open label treatment

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity

Description

Time Frame

Least Mean Squares Double-blind phase: change from baseline to week 24

Title

Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity

Description

Time Frame

Least mean squares for Open Label: Change between weeks 24-48

Secondary Outcome Measure Information:

Title

Change in Sociability Factor (SF)

Description

Time Frame

Double-blind phase: change in least means squares between week 0 & 24.

Title

Change in Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score

Description

Time Frame

Double-blind phase: baseline, weeks 12, 24

Title

Change in Stanford Binet-5th Edition (SB-5) IQ Score

Description

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.

Time Frame

Double-blind phase: baseline to week 24

Other Pre-specified Outcome Measures:

Title

Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score

Description

Time Frame

Open Label: weeks 24, 48

Title

Change in Vineland II Adaptive Behavior Scales (VABS-II) Daily Living Domain Score

Description

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.

Time Frame

Double-blind phase: baseline, week 24; Open Label: week 48

Title

Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Mean Score

Description

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.

Time Frame

Open Label: weeks 24, 48

Title

Change in Vineland II Adaptive Behavior Scales (VABS-II) Communication Domain Score

Description

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.

Time Frame

Double-blind phase: baseline, week 24; Open Label: week 48

Title

Change in Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Score

Description

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.

Time Frame

Double-blind phase: baseline, week 24

Title

Change in Vineland II Adaptive Behavior Scales (VABS-II) Socialization Domain Score

Description

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.

Time Frame

Double-blind phase: baseline, week 24; Open Label: week 48

Title

Change in Caregiver Strain Questionnaire (CSQ) Objective Subscale Score

Description

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.

Time Frame

Double-blind phase: baseline, week 24; Open Label: week 48

Title

Change in Caregiver Strain Questionnaire (CSQ) Subjective Externalizing Subscale Score

Description

Time Frame

Double-blind phase: baseline, week 24; Open Label: week 48

Title

Change in Vineland II Adaptive Behavior Scales (VABS-II) Composite Score

Description

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.

Time Frame

Double-blind phase: baseline, week 24

Title

Change in Clinical Global Impressions -Improvement Score (CGI-I)

Description

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

Time Frame

Double blind phase: change from Baseline to week 12, and week 24. Open label phase change from week 24 to week 48

Title

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.

Description

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.

Time Frame

Double blind phase: change from Baseline and week 24. Note: only those who demonstrated understanding of these concepts were included in sample.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility 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 -added part way through study in response to subject death.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Linmarie Sikich, MD

Organizational Affiliation

Duke University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Lurie Center for Autism, Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Mount Sinai School of Medicine

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

Facility Name

Center for Autism and the Developing Brain

City

White Plains

State/Province

New York

ZIP/Postal Code

10605

Country

United States

Facility Name

Duke Center for Autism and Brain Development

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27705

Country

United States

Facility Name

Duke University , Genetics Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

Vanderbilt University

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37212

Country

United States

Facility Name

Seattle Children's Hospital Research Institute

City

Seattle

State/Province

Washington

ZIP/Postal Code

98105

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Most data will be available on NDAR, but will not be identifiable.

Citations:

PubMed Identifier

32777383

Citation

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.

Results Reference

background

PubMed Identifier

34644471

Citation

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.

Results Reference

derived

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Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors

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