Intranasal Oxytocin for the Treatment of Children and Adolescents With ASD (OXY)
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 investigators of this study have previously documented: 1) an association between Autism Spectrum Disorder 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 Autism Spectrum Disorder in childhood is highly valuable because it could influence the developmental trajectory and make further psychosocial interventions possible. In this context, we propose a small dose finding study to confirm that the dose used in the adult study is not more than the maximum tolerated dose in youth. `
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Intranasal Oxytocin for the Treatment of Children and Adolescents With Autism Spectrum Disorders (ASD)|
- Maximum Tolerated Dose (MTD) [ Time Frame: 12 Weeks ] [ Designated as safety issue: Yes ]The hypothesis is that the maximum tolerated dose in a range of 0.2-0.4 IU/kg / dose will be 0.4 IU/kg / dose, as was the case in the adult study, given that oxytocin is not stored in body fat and does not depend on liver or renal clearance.
- Number of Participants With Serious Adverse Events [ Time Frame: 24 Weeks ] [ Designated as safety issue: Yes ]This will be reported as the number of participants who experienced a serious advert event throughout the study.
- Baseline Levels of Oxytocin in Relation to Either Safety or Treatment Response [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]Children and adolescents with lower plasma oxytocin levels at baseline will show treatment related changes in social cognition. Children and adolescents with higher oxytocin plasma levels will show diminished or less dramatic treatment responses and may have more difficulty tolerating the treatment.
- Blood Levels of Oxytocin During the Trial in Relation to Safety or Treatment Response [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]Children and adolescents with minimal changes in plasma level of oxytocin after treatment will be less responsive to treatment. Children and adolescents with atypical patterns of increase in oxytocin may be more sensitive to dose-related tolerability.
- Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
Social Cognition (higher score=positive response)
- Let's Face It Skills Battery; i. Matchmaker (0-100); ii. Faces (0-100); iii. Houses (0-100)
- Eyes Test (0-28)
- Strange Stories (0-16)
- Irony and Empathy (0-24)
- Aberrant Behavior Checklist (0-48) (lower score=positive response)
- Behavioral Assessment System for Children (higher score=positive response); i. Social: age 8 to 11 & 15 to 18 (18-69); age 12 to 14 (21-70); ii. Functional: age 8 to 14 (10-66); age 15 to 18 (10-64)
- Social Responsiveness Scale (higher score=positive response); male (34-127); female (35-142)
Anxiety (lower score=positive response)
a. Child Symptom Inventory; i. Separation: male (44-106); female (44-101); ii. Generalized: male (40-101); female (41-96)
Repetitive Behaviors (lower score=positive response)
- Child Yale-Brown Obsessive-Compulsive Scale (0-20)
- Repetitive Behavior Scale (0-129)
Measures insensitive to change will be omitted from results.
- Measures of Social Function - The Clinical Global Impressions - Social Scale (Baseline to Week 12) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
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).
|Study Start Date:||November 2010|
|Study Completion Date:||March 2013|
|Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
Experimental: Intanasal Oxytocin
A modified dose finding method will be used to determine safety among four dose levels for Intranasal Oxytocin. Half the dose (0.2 IU/kg /dose) is the minimum dose and two intermediate doses will also be evaluated (0.26 and 0.33 IU/kg / dose) Dose-finding escalations will be done in groups of three patients.Three patients will be studied at the first dose level. If none of these patients experience dose limiting toxicity, the dose will be escalated. If one experiences dose limiting toxicity, up to three more will be accrued at the same level. If none of these experience dose limiting toxicity, the dose will be escalated. If one or more of these experience dose-limiting toxicity, entry at that dose level will be stopped. Up to three more patients will be treated at the next lower dose. If zero out of these experience dose limiting toxicity, an additional three patients will be treated at that dose.
Drug: Intranasal Oxytocin
We are selecting morning and afternoon dosing to try to influence most hours where youth are in settings with increased potential for social interaction (school, after school). Medication will be administered by the parents before school and early afternoon. All patients will receive their first dose by the study physician to educate parents and themselves on proper administration and determine safety of first dose.
Other Name: Syntocinon
Please refer to this study by its ClinicalTrials.gov identifier: NCT01256060
|Holland Bloorview Kids Rehabilitation Hospital|
|Toronto, Ontario, Canada, M4G 1R8|
|Principal Investigator:||Evdokia Anagnostou, MD||Holland Bloorview Kids Rehabilitation Hospital|
|Principal Investigator:||Suma Jacob, MD, PhD||University of Illinois at Chicago|
|Principal Investigator:||Jessica Brian, PhD||Holland Bloorview Kids Rehabilitation Hospital|
|Principal Investigator:||Wendy Roberts, MD||The Hospital for Sick Children|
|Principal Investigator:||Sharon Smile, MD||Holland Bloorview Kids Rehabilitation Hospital|
|Principal Investigator:||Edwin Cook, MD||University of Illinois at Chicago|
|Principal Investigator:||Annie Dupuis, PhD||Holland Bloorview Kids Rehabilitation Hospital|
|Principal Investigator:||Margot Taylor, PhD||The Hospital for Sick Children|