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

This study has been completed.
Sponsor:
Collaborators:
Holland Bloorview Kids Rehabilitation Hospital
The Hospital for Sick Children
University of Illinois at Chicago
Information provided by (Responsible Party):
Evdokia Anagnostou, Anagnostou, Evdokia, M.D.
ClinicalTrials.gov Identifier:
NCT01256060
First received: November 22, 2010
Last updated: April 13, 2015
Last verified: April 2015
  Purpose

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. `


Condition Intervention Phase
Autism Spectrum Disorder
Drug: Intranasal Oxytocin
Phase 2

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by Anagnostou, Evdokia, M.D.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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)

    1. Let's Face It Skills Battery; i. Matchmaker (0-100); ii. Faces (0-100); iii. Houses (0-100)
    2. Eyes Test (0-28)
    3. Strange Stories (0-16)
    4. Irony and Empathy (0-24)

    Social Function

    1. Aberrant Behavior Checklist (0-48) (lower score=positive response)
    2. 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)
    3. 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)

    1. Child Yale-Brown Obsessive-Compulsive Scale (0-20)
    2. 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 ]

    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).



Enrollment: 15
Study Start Date: November 2010
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   10 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01256060

Locations
Canada, Ontario
Holland Bloorview Kids Rehabilitation Hospital
Toronto, Ontario, Canada, M4G 1R8
Sponsors and Collaborators
Evdokia Anagnostou
Holland Bloorview Kids Rehabilitation Hospital
The Hospital for Sick Children
University of Illinois at Chicago
Investigators
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
  More Information

No publications provided

Responsible Party: Evdokia Anagnostou, Principal Investigator, Anagnostou, Evdokia, M.D.
ClinicalTrials.gov Identifier: NCT01256060     History of Changes
Other Study ID Numbers: 10-001
Study First Received: November 22, 2010
Results First Received: January 13, 2015
Last Updated: April 13, 2015
Health Authority: Canada: Health Canada

Keywords provided by Anagnostou, Evdokia, M.D.:
Autism Spectrum disorder
Oxytocin
Clinical Trial
Children
Pharmacology

Additional relevant MeSH terms:
Child Development Disorders, Pervasive
Mental Disorders
Mental Disorders Diagnosed in Childhood
Oxytocin
Oxytocics
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 03, 2015