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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Intranasal Oxytocin

About this trial

This is an interventional treatment trial for Autism Spectrum Disorder focused on measuring Autism Spectrum disorder, Oxytocin, Clinical Trial, Children, Pharmacology

Eligibility Criteria

10 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Holland Bloorview Kids Rehabilitation Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intanasal Oxytocin

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT01256060

First Posted

November 22, 2010

Last Updated

July 12, 2016

Sponsor

Evdokia Anagnostou

Collaborators

Holland Bloorview Kids Rehabilitation Hospital, The Hospital for Sick Children, University of Illinois at Chicago

1. Study Identification

Unique Protocol Identification Number

NCT01256060

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2016

Overall Recruitment Status

Completed

Study Start Date

November 2010 (undefined)

Primary Completion Date

March 2013 (Actual)

Study Completion Date

March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Evdokia Anagnostou

Collaborators

Holland Bloorview Kids Rehabilitation Hospital, The Hospital for Sick Children, University of Illinois at Chicago

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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. '

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autism Spectrum Disorder

Keywords

Autism Spectrum disorder, Oxytocin, Clinical Trial, Children, Pharmacology

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intanasal Oxytocin

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Intranasal Oxytocin

Other Intervention Name(s)

Syntocinon

Intervention Description

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.

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD)

Description

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.

Time Frame

12 Weeks

Title

Number of Participants With Serious Adverse Events

Description

This will be reported as the number of participants who experienced a serious advert event throughout the study.

Time Frame

24 Weeks

Secondary Outcome Measure Information:

Title

Baseline Levels of Oxytocin in Relation to Either Safety or Treatment Response

Description

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.

Time Frame

12 Weeks

Title

Blood Levels of Oxytocin During the Trial in Relation to Safety or Treatment Response

Description

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.

Time Frame

12 Weeks

Other Pre-specified Outcome Measures:

Title

Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)

Description

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.

Time Frame

12 Weeks

Title

Measures of Social Function - The Clinical Global Impressions - Social Scale (Baseline to Week 12)

Description

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).

Time Frame

12 Weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

10 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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.

Overall Study Officials: