Intranasal Oxytocin for the Treatment of Children and Adolescents With ASD (OXY)

Study Overview
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Brief Summary
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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. '

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

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Intranasal Oxytocin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female outpatients 10-17 years of age inclusive. Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria for Autistic Disorder or Asperger's Disorder as established by a clinician and supported by the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview - Revised. Have a Clinician's Global Impression-Severity score ≥ 4 (moderately ill) at Baseline. Verbal Intelligent Quotient >/= 70. If already receiving stable pharmacological and or non-pharmacologic educational, behavioral, and/or dietary interventions, have continuous participation during the preceding 3 months prior to Screening and will 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 clinically insignificant by the Investigator. The participant and caregiver must be able to speak and understand English sufficiently to allow for the completion of all study assessments. Exclusion Criteria: Patients born prior to 35 weeks gestational age. Patients with any primary psychiatric diagnosis other than autism at Screening. Patients with current 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 MRI/structural lesion of the brain. Pregnant female patients, sexually active female patients on hormonal birth control and sexually active females who do not use two types of non-hormonal birth control Patients with a medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease. Patients who are sensitive to Syntocinon or any components of its formulation 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 unable to tolerate venipuncture procedures for blood sampling.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intanasal Oxytocin<br>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<br>* 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.<br>* Other names: Syntocinon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | 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. | 12 Weeks | 
| Number of Participants With Serious Adverse Events | This will be reported as the number of participants who experienced a serious advert event throughout the study. | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Levels of Oxytocin in Relation to Either Safety or Treatment Response | 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. | 12 Weeks | 
| Blood Levels of Oxytocin During the Trial in Relation to Safety or Treatment Response | 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. | 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism Spectrum disorder, Oxytocin, Clinical Trial, Children, Pharmacology