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: June 19, 2014
Last verified: June 2014
  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 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.


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:
  • 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.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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 ]

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
  1. Three patients are studied at the first dose level
  2. If none of these patients experience dose limiting toxicity (DLT), then the dose is escalated to the next higher level in the three subsequent patients.
  3. If one of three patients experiences DLT, then up to three more patients are accrued at the same level. a) If none of the additional patients experience DLT, then the dose is escalated in subsequent patients. b) If one or more of the additional patients experiences DLT, the MTD has been exceeded and dose escalation will be stopped. Up to three more patients are treated at the next lower dose. If two or more of a cohort of up to six patients experience DLT at a given dose level, then the MTD has been exceeded and dose escalation will be stopped. Up to three more patients are treated at the next lower dose. If zero out of three patients experience DLT at a dose of 0.4UI/kg, 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, 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

  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. DSM-IV criteria for Autistic Disorder or Asperger's Disorder will be established by a clinician with expertise with individuals with ASD. Best estimate Diagnosis will be reached using DSM IV criteria, the Autism Diagnostic Observation Schedule (ADOS-G) and the Autism Diagnostic Interview (ADI-R)
  3. Have a Clinician's Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Baseline.
  4. Verbal IQ >/= 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, HBV, HCV, hemophilia (bleeding problems, recent nose and brain injuries), abnormal blood pressure (hypotension or hypertension), drug abuse (meets DSM criteria), 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
Last Updated: June 19, 2014
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
Disease
Mental Disorders Diagnosed in Childhood
Mental Disorders
Pathologic Processes
Oxytocin
Oxytocics
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014