Clinical trial NCT01944046: Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors
Official title: Phase II Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autism Spectrum Disorders
Keywords: autism, ASD, autistic, Asperger's, PDD-NOS, oxytocin
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2013-09-17
Enrollment: 290
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity
timeFrame: Least Mean Squares Double-blind phase: change from baseline to week 24
measure: Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity
timeFrame: Least mean squares for Open Label: Change between weeks 24-48
Secondary outcomes:
measure: Change in Sociability Factor (SF)
timeFrame: Double-blind phase: change in least means squares between week 0 & 24.
measure: Change in Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score
timeFrame: Double-blind phase: baseline, weeks 12, 24
measure: Change in Stanford Binet-5th Edition (SB-5) IQ Score
timeFrame: Double-blind phase: baseline to week 24
Other outcomes:
measure: Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score
timeFrame: Open Label: weeks 24, 48
measure: Change in Vineland II Adaptive Behavior Scales (VABS-II) Daily Living Domain Score
timeFrame: Double-blind phase: baseline, week 24; Open Label: week 48
measure: Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Mean Score
timeFrame: Open Label: weeks 24, 48
measure: Change in Vineland II Adaptive Behavior Scales (VABS-II) Communication Domain Score
timeFrame: Double-blind phase: baseline, week 24; Open Label: week 48
measure: Change in Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Score
timeFrame: Double-blind phase: baseline, week 24
measure: Change in Vineland II Adaptive Behavior Scales (VABS-II) Socialization Domain Score
timeFrame: Double-blind phase: baseline, week 24; Open Label: week 48
measure: Change in Caregiver Strain Questionnaire (CSQ) Objective Subscale Score
timeFrame: Double-blind phase: baseline, week 24; Open Label: week 48
measure: Change in Caregiver Strain Questionnaire (CSQ) Subjective Externalizing Subscale Score
timeFrame: Double-blind phase: baseline, week 24; Open Label: week 48
measure: Change in Vineland II Adaptive Behavior Scales (VABS-II) Composite Score
timeFrame: Double-blind phase: baseline, week 24
measure: Change in Clinical Global Impressions -Improvement Score (CGI-I)
timeFrame: Double blind phase: change from Baseline to week 12, and week 24. Open label phase change from week 24 to week 48
measure: 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.
timeFrame: Double blind phase: change from Baseline and week 24. Note: only those who demonstrated understanding of these concepts were included in sample.
Locations:
city: Boston
country: United States
facility: Lurie Center for Autism, Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: White Plains
country: United States
facility: Center for Autism and the Developing Brain
state: New York
city: Durham
country: United States
facility: Duke Center for Autism and Brain Development
state: North Carolina
city: Durham
country: United States
facility: Duke University , Genetics Center
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Seattle
country: United States
facility: Seattle Children's Hospital Research Institute
state: Washington
Study officials:
affiliation: Duke University
name: Linmarie Sikich, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.