Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors (SOARS-B)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01944046 |
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Recruitment Status :
Completed
First Posted : September 17, 2013
Results First Posted : January 5, 2021
Last Update Posted : January 5, 2021
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Sponsor:
Linmarie Sikich
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Linmarie Sikich, Duke University
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Autism Spectrum Disorders | Drug: Double blind phase Placebo Nasal Spray Drug: double Blind Oxytocin Nasal Spray Drug: Open Label intranasal oxytocin | Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 290 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention 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: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | Quadruple |
| Primary Purpose: | Treatment |
| Official Title: | Phase II Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors |
| Actual Study Start Date : | August 1, 2014 |
| Actual Primary Completion Date : | November 30, 2017 |
| Actual Study Completion Date : | November 30, 2017 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Autism spectrum disorder
Drug Information available for:
Oxytocin
| Arm | Intervention/treatment |
|---|---|
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Placebo Comparator: DB Placebo Nasal Spray
Placebo treatment during weeks 0-24 double blind phase
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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 Name: DB Placebo (PL) |
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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
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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 Name: DB Intranasal Oxytocin (OT) |
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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
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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 Name: open label treatment |
Primary Outcome Measures :
- Change in Aberrant Behavior Checklist-Social Withdrawal Subscale ABC-SW, a Measure of Reciprocal Social Behavior [ Time Frame: Double-blind phase: baseline, weeks 4, 8, 12, 16, 20, 24 ]The primary outcome is Change in Aberrant Behavior Checklist-Social Withdrawal subscale- a measure ofreciprocal social behaviors. ABC-SW is a modification of the ABC-Lethargy subscale. The ABC-SW 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 higher level of social withdrawal.
- ABC-SW (Aberrant Behavior Checklist-Social Withdrawal) Subscale - Reciprocal Social Behavior [ Time Frame: Least mean squares for Open Label: weeks 24 -48 ]The ABC-SW 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.
- Change in Sociability Factor (SF) [ Time Frame: 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. NOTE THIS MEASURE WAS ELIMINATED FROM FINAL SAP'S
Secondary Outcome Measures :
- Change in Social Reciprocity Scale-2 (SRS-2) Social Motivation Subscale Score [ Time Frame: 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.
- Social Reciprocity Scale-2 (SRS-2) Social Motivation Subscale Score [ Time Frame: Open Label: weeks 24, 48 ]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 [ Time Frame: 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.
- Change in Vineland II Adaptive Behavior Scales (VABS-II) Composite Score [ Time Frame: Double-blind phase: baseline, week 24 ]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.
- Change in Vineland II Adaptive Behavior Scales (VABS-II) Socialization Domain Score [ Time Frame: Double-blind phase: baseline, week 24; Open Label: week 48 ]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.
- Change in Vineland II Adaptive Behavior Scales (VABS-II) Daily Living Domain Score [ Time Frame: Double-blind phase: baseline, week 24; Open Label: week 48 ]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.
- Change in Vineland II Adaptive Behavior Scales (VABS-II) Communication Domain Score [ Time Frame: Double-blind phase: baseline, week 24; Open Label: week 48 ]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.
- Change in Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Score [ Time Frame: Double-blind phase: baseline, week 24 ]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.
- Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Mean Score [ Time Frame: Open Label: weeks 24, 48 ]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.
- Change in Caregiver Strain Questionnaire (CSQ) Subjective Externalizing Subscale Score [ Time Frame: Double-blind phase: baseline, week 24; Open Label: week 48 ]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.
- Change in Caregiver Strain Questionnaire (CSQ) Objective Subscale Score [ Time Frame: Double-blind phase: baseline, week 24; Open Label: week 48 ]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.
Other Outcome Measures:
- Changes in Biologic Outcome Measures [ Time Frame: Double blind phase: change from Baseline to week 8, and week 24. Open label phase change from week 24 to week 36. ]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 Clinical Global Impressions -Improvement Score (CGI-I) [ Time Frame: Double blind phase: change from Baseline to week 12, and week 24. Open label phase change from week 24 to week 48 ]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
- 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. [ Time Frame: Double blind phase: change from Baseline and week 24. Note: only those who demonstrated understanding of these concepts were included in sample. ]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.
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| 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 -added part way through study in response to subject death.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 | |
| 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 |
Study Documents (Full-Text)
Documents provided by Linmarie Sikich, Duke University:
Documents provided by Linmarie Sikich, Duke University:
Study Protocol and Statistical Analysis Plan [PDF] March 21, 2016
Publications:
| Responsible Party: | Linmarie Sikich, Associate professor, Duke University |
| ClinicalTrials.gov Identifier: | NCT01944046 |
| Other Study ID Numbers: |
Pro00063950 1U01HD073984 ( U.S. NIH Grant/Contract ) 13-0593 ( Other Identifier: UNC ) |
| First Posted: | September 17, 2013 Key Record Dates |
| Results First Posted: | January 5, 2021 |
| Last Update Posted: | January 5, 2021 |
| Last Verified: | December 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | Most data will be available on NDAR, but will not be identifiable. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Linmarie Sikich, Duke University:
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autism, ASD, autistic, Asperger's, PDD-NOS, oxytocin |
Additional relevant MeSH terms:
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Autistic Disorder Autism Spectrum Disorder Child Development Disorders, Pervasive Neurodevelopmental Disorders Mental Disorders |
Oxytocin Oxytocics Reproductive Control Agents Physiological Effects of Drugs |