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 PI of this study and the PI of the UIC subcontract 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 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)|
- To determine the maximum tolerated dose to be used in the randomized study of intranasal oxytocin [ Time Frame: 24 Weeks ] [ Designated as safety issue: Yes ]The hypothesis is that the maximum tolerated dose in a range of .02-0.4IU/kg bid will be 0.4IU/kg bid, 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.
- To examine the safety and tolerability of intranasal oxytocin in youth with ASD [ Time Frame: 24 Weeks ] [ Designated as safety issue: Yes ]Safety and tolerability will be assessed through the Clinical Global Impressions Scale - Improvement (CGI-I) and the Safety Monitoring Uniform Report Form (SMURF). The CGI-I employs a seven point (1 = very much improved to 7 = very much worse) to determine the patient's improvement in response to treatment. We will also be using the Wide Range Assessment of Memory and Learning (WRAML) as a safety measure, to monitor memory performance given that some of the animal models have suggested a possible amnestic effect of oxytocin.
- To examine whether baseline levels of oxytocin are related 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.
- 4. To examine whether changes of blood levels of oxytocin during the trial are related 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.
- We will pilot what other measures best capture changes in social cognition and function in ASD. This will help us clarify which measures should be used in a double blind randomized control trial [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
|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
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, afterschool). 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|