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

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

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 Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: Intranasal Oxytocin

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4G 1R8
      • Holland Bloorview Kids Rehabilitation Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female outpatients 10-17 years of age inclusive.
2. 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.
3. Have a Clinician's Global Impression-Severity score ≥ 4 (moderately ill) at Baseline.
4. Verbal Intelligent Quotient >/= 70.
5. 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.
6. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigator.
7. The participant and caregiver must be able to speak and understand English sufficiently to allow for the completion of all study assessments.

Exclusion Criteria:

1. Patients born prior to 35 weeks gestational age.
2. Patients with any primary psychiatric diagnosis other than autism at Screening.
3. 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.
4. 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
5. 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.
6. Patients who are sensitive to Syntocinon or any components of its formulation
7. 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.
8. Patients unable to tolerate venipuncture procedures for blood sampling.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 Names: Syntocinon

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)	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) Social Function; 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.	12 Weeks
Measures of Social Function - The Clinical Global Impressions - Social Scale (Baseline to Week 12)	Social Function 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

Collaborators and Investigators

• Sponsor: Evdokia Anagnostou
• Collaborators: The Hospital for Sick Children; University of Illinois at Chicago; Holland Bloorview Kids Rehabilitation Hospital
• Investigators: Principal Investigator: Evdokia Anagnostou, M.D., Holland Bloorview Kids Rehabilitation Hospital; Principal Investigator: Suma Jacob, M.D., Ph.D., University of Illinois at Chicago; Principal Investigator: Jessica Brian, Ph.D., Holland Bloorview Kids Rehabilitation Hospital; Principal Investigator: Wendy Roberts, M.D., The Hospital for Sick Children; Principal Investigator: Sharon Smile, M.D., Holland Bloorview Kids Rehabilitation Hospital; Principal Investigator: Edwin Cook, M.D., University of Illinois at Chicago; Principal Investigator: Annie Dupuis, Ph.D., Holland Bloorview Kids Rehabilitation Hospital; Principal Investigator: Margot Taylor, Ph.D., The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: November 22, 2010
• First Submitted That Met QC Criteria: December 7, 2010
• First Posted (Estimate): December 8, 2010

Study Record Updates

• Last Update Posted (Estimate): August 12, 2016
• Last Update Submitted That Met QC Criteria: July 12, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Children; Oxytocin; Clinical Trial; Pharmacology; Autism Spectrum disorder
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: 10-001