Intranasal Oxytocin for the Treatment of Children and Adolescents With Autism Spectrum Disorders (ASD)

Study Overview
=================
Brief Summary
-----------------
We are studying an investigational drug called intranasal oxytocin (Syntocinon®). Syntocinon® has been approved by the U.S. Food and Drug Administration for use in helping women breastfeed, but it has not been approved for use in children with ASD. However, there is previous research conducted that has indicated that after administration of oxytocin, adults with ASD demonstrated improvements in social cognition, and reduced repetitive behaviours and anxiety. There is also early research to suggest that children may also benefit in these areas. The purpose of this study is to test if oxytocin works to help children and adolescents with ASD.

Detailed Description
-----------------
Extensive data has been accumulated to suggest that central release of oxytocin is important for social cognition and function, as well as likely involved in anxiety modulation and repetitive behaviors. The Principal Investigator and Co-Principal Investigator of this study have previously documented: 1) an association between ASD and a single nuclear polymorphism of the oxytocin receptor gene, 2) ability to measure oxytocin levels in the blood by enzyme immunoassay and 3) preliminary data to support safety and efficacy of intranasal oxytocin in the treatment of social deficits and repetitive behaviors in adults with autism. A medication treatment targeting the core deficits of ASD in childhood is highly valuable because it could influence the developmental trajectory and make further psychosocial interventions possible. In this context, we propose a randomized placebo controlled trial of intranasal oxytocin in children and adolescents with ASD.

Official Title
-----------------
Intranasal Oxytocin for the Treatment of Children and Adolescents With Autism

Conditions
-----------------
Autism Spectrum Disorder

Intervention / Treatment
-----------------
* Drug: Intranasal Oxytocin
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Male or female outpatients, 10-17 years of age inclusive. Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Diagnostic and Statistical Manual (DSM-IV) criteria will be established by a clinician with expertise with individuals with ASD. Best estimate Diagnosis will be reached using DSM-IV criteria, the Autism Diagnostic Observation Schedule (ADOS-2) and the Autism Diagnostic Interview (ADI-R). Have a Clinician's Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Screening. Verbal and performance scale Intelligence Quotient (IQ) ≥ 70 (both subtests of the Wechsler Abbreviated Scale of Intelligence (WASI-I or WASI-II ≥ 70). If already receiving stable concomitant medications affecting behavior, have continuous participation for 1 month prior to Screening (with the exception of fluoxetine, where a period of 6 weeks is needed), and not electively initiate new or modify ongoing medications for the duration of the study. If already receiving stable non-pharmacologic educational, behavioral, and/or dietary interventions, have continuous participation during the preceding 3 months prior to Screening, and not electively initiate new or modify ongoing interventions for the duration of the study. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed not clinically significant by the Treating Clinician. Ability to speak and understand English sufficiently to allow for the completion of all study assessments. Ability to obtain written informed consent from the participant, if developmentally appropriate. If a participant does not have the capacity to consent, ability to obtain assent (if developmentally appropriate), as well as written informed consent from their parent(s)/legal guardian. Exclusion Criteria Patients born prior to 35 weeks gestational age. Patients with a primary psychiatric diagnosis other than ASD. Patients with a medical history of neurological disease, including, but not limited to, epilepsy/seizure disorder (except simple febrile seizures), movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes, or known abnormal brain MRI/structural lesion. Pregnant female patients, sexually active female patients on hormonal birth control and sexually active females who do not use at least two types of non-hormonal birth control. Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease. Patients with one or more of the following: HIV, Hepatitis B virus, Hepatitis C virus, hemophilia (bleeding problems, recent nose and brain injuries), abnormal blood pressure (hypotension or hypertension), drug abuse, immunity disorder or severe depression. Patients who are currently taking oxytocin or have taken intranasal oxytocin in the past with no response. Patients with a sensitivity to oxytocin or any components of its formulation. Patients unable to tolerate venipuncture procedures for blood sampling. Patients in foster care for whom the province/state is defined as a legal guardian

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intranasal Oxytocin (Syntocinon)<br>The proposed dosing schedule is 0.4 IU/kg, taken twice daily, for a maximum of 24 IUs per dose | Drug: Intranasal Oxytocin<br> <br> * Other names: Syntocinon;|
| Placebo Comparator: Placebo<br>The proposed dosing schedule is 0.4 IU/kg, taken twice daily, for a maximum of 24 IUs per dose | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Intranasal Oxytocin vs. Placebo on Measures of Social Function | This will be measured by a change in score on the Aberrant Behavior Checklist (ABC) - Social Withdrawal Subscale (0-48, where lower scores indicate improvement) | 12 and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Intranasal Oxytocin vs. Placebo on Measures of Social Cognition | This will be measured by a change in score the Revised Eyes Test (0- 28; where higher scores indicate better performance/improvement) Baseline to Week 12 | 12 Weeks | 
| Efficacy of Intranasal Oxytocin vs. Placebo on Measures of Social Cognition | This will be measured by improvement on the Let's Face it! Skills Battery from Baseline to Week 12 Social Cognition (higher score=better outcome) a. Let's Face It Skills Battery; i. Matchmaker (0-100); ii. Faces (0-100); iii. Houses (0-100) | 12 Weeks | 
| Efficacy of Intranasal Oxytocin vs. Placebo on Measures of Social Function | This will be measured by improvement on the Behavioral Assessment System for Children (BASC-2) from Baseline to Week 12 Behavioral Assessment System for Children (higher score=positive response); i. *Social Skills: age 6 to 11 (18-69); age 12 to 17 (21-70); ii. Functional Communication: age 6 to 11 (10-66); age 12 to 17 (10-64); iii. Withdrawal age 6-11 (21- 62) ; age 12-17 (14-42) * only social subscales of BASC-2 reported | 12 Weeks | 
| Number of Participant Considered Social Responders | This will be measured by the Clinical Global Impressions - Improvement Scale - Social (CGI-I-Social) a) Clinical Global Impressions - Social Scale (1-7) (lower score=positive response). The results will be reported as the number of participants that were classified as a social responder (achieving a score of 1 or 2 on the scale). | 12 Weeks | 
| Efficacy of Intranasal Oxytocin vs. Placebo on Measures of Repetitive Behaviors | This will be measured by improvement on the Child Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) from Baseline to Week 12 -lower score= positive response (0-20) | 12 Weeks | 
| Efficacy of Intranasal Oxytocin vs. Placebo on Measures of Repetitive Behaviors | This will be measured by improvement on the Repetitive Behavior Scale (RBS-R)(0-129; where lower score= positive response) from Baseline to Week 12 | 12 Weeks | 
| Efficacy of Intranasal Oxytocin vs. Placebo on Measures of Anxiety | This will be measured by the Child and Adolescent Symptom Inventory (CASI-4R) Generalized anxiety score (male (40-101); female (41-96) -where lower score= positive response) from Baseline to Week 12 | 12 Weeks | 
| Efficacy of Intranasal Oxytocin vs. Placebo on Measures of Quality of Life | This will be measured by improvement on the Pediatric Quality of Life Inventory (PedsQL) (0-100, where higher scores indicate positive response) from Baseline to Week 12 | 12 Weeks | 
| Number of Participant Considered Overall Responders | This will be measured by the Clinical Global Impressions - Improvement Scale - Global (CGI-I-Global) (1-7) (lower score=positive response). The results will be reported as the number of participants that were classified as an overall responder (achieving a score of 1 or 2 on the scale). | 12 Weeks | 
| Safety and Tolerability of Intranasal Oxytocin in Children and Adolescents With ASD | This will be measured by the Safety Monitoring Uniform Report Form (SMURF) | 12 Weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Autism, Social, Functioning, Cognition, Repetitive Behaviors, Anxiety, Quality of Life