Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors

NCT01944046 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: Pro000639501U01HD07398413-0593
• Study Type: interventional
• Target: 290
• Locations: 1 country
• Sites: 7

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.

Conditions

Autism Spectrum Disorders

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Change in Sociability Factor (SF)

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

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

  Double-blind phase: baseline, weeks 12, 24

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

  Double-blind phase: baseline to week 24

Other Outcomes (11)

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

  Open Label: weeks 24, 48

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

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

• Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Mean Score

  Open Label: weeks 24, 48

Study Arms (3)

DB Placebo Nasal Spray

PLACEBO COMPARATOR

Placebo treatment during weeks 0-24 double blind phase

Drug: Double blind phase Placebo Nasal Spray

DB Oxytocin Nasal Spray

ACTIVE COMPARATOR

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

open label intranasal oxytocin

ACTIVE COMPARATOR

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

Interventions

Double blind phase Placebo Nasal Spray DRUG

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.

Also known as: DB Placebo (PL)

DB Placebo Nasal Spray

double Blind Oxytocin Nasal Spray DRUG

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.

Also known as: DB Intranasal Oxytocin (OT)

DB Oxytocin Nasal Spray

Open Label intranasal oxytocin DRUG

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

Also known as: open label treatment

open label intranasal oxytocin

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Linmarie Sikich: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (7)

Lurie Center for Autism, Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Center for Autism and the Developing Brain

White Plains, New York, 10605, United States

Location

Duke Center for Autism and Brain Development

Durham, North Carolina, 27705, United States

Location

Duke University , Genetics Center

Durham, North Carolina, 27710, United States

Location

Vanderbilt University

Nashville, Tennessee, 37212, United States

Location

Seattle Children's Hospital Research Institute

Seattle, Washington, 98105, United States

Location

Related Publications (3)

• 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.

  PMID: 32777383 BACKGROUND

• Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.

  PMID: 37811711 DERIVED

• 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.

  PMID: 34644471 DERIVED

MeSH Terms

Conditions

Autism Spectrum Disorder; Autistic Disorder

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Results Point of Contact

• Title: Linmarie Sikich, M.D.
• Organization: Duke University

linmarie.sikich@duke.edu

919-681-0026

Study Officials

• Linmarie Sikich, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate professor

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

Study Record Dates

• First Submitted: June 13, 2013
• First Posted: September 17, 2013
• Study Start: August 1, 2014
• Primary Completion: November 30, 2017
• Study Completion: November 30, 2017
• Last Updated: June 18, 2021
• Results First Posted: January 5, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)