Trial Outcomes & Findings for Intranasal Oxytocin for the Treatment of Children and Adolescents With ASD (OXY) (NCT NCT01256060)
NCT ID: NCT01256060
Last Updated: 2016-08-12
Results Overview
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.
COMPLETED
PHASE2
15 participants
12 Weeks
2016-08-12
Participant Flow
Participants were recruited from the hospital clinical database, as well as presentations at local conferences and media. Diagnosis was established using the Diagnostic and Statistical Manual, Fourth Edition for an Autism Spectrum Disorder supported by the Autism Diagnostic Observations Schedule and the Autism Diagnostic Interview - Revised.
Cohort 1 Dosage: 0.20 IU/kg - 3 participants Cohort 2 Dosage: 0.26 IU/kg - 3 participants Cohort 3 Dosage: 0.33 IU/kg - 3 participants Cohort 4 Dosage: 0.40 IU/kg - 6 participants
Participant milestones
| Measure |
0.2 IU / kg
|
0.26 IU / kg
|
0.33 IU / kg
|
0.4 IU / kg
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
3
|
6
|
|
Overall Study
COMPLETED
|
3
|
2
|
3
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
0.2 IU / kg
|
0.26 IU / kg
|
0.33 IU / kg
|
0.4 IU / kg
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Intranasal Oxytocin for the Treatment of Children and Adolescents With ASD (OXY)
Baseline characteristics by cohort
| Measure |
Intanasal Oxytocin
n=15 Participants
A modified dose finding method was used to determine safety among four dose levels. Half the dose (0.2 IU/kg /dose) was the minimum dose and two intermediate doses were also evaluated (0.26 and 0.33 IU/kg / dose) Dose-finding escalations were done in groups of three patients.
1. Three patients were studied at the first dose level
2. If none of these patients experienced dose limiting toxicity, the dose was escalated.
3. If one patient experienced dose limiting toxicity, up to three more patients were accrued at the same level. (a) If none of these patients experienced dose limiting toxicity, the dose was escalated. (b) If one or more experienced dose-limiting toxicity, entry at that dose level would be stopped, the maximum tolerated dose exceeded, and dose escalation would be stopped. Up to three more patients would be treated at the next lower dose. If zero out of three patients experience dose limiting toxicity, an additional three patients were to be treated at that dose.
|
|---|---|
|
Age, Categorical
<=18 years
|
15 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
15 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 WeeksThe 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.
Outcome measures
| Measure |
Intanasal Oxytocin
n=15 Participants
Cohort 1 Dosage: 0.20 IU/kg - 3 participants Cohort 2 Dosage: 0.26 IU/kg - 3 participants Cohort 3 Dosage: 0.33 IU/kg - 3 participants Cohort 4 Dosage: 0.40 IU/kg - 6 participants
|
|---|---|
|
Maximum Tolerated Dose (MTD)
|
0.40 IU / kg
|
PRIMARY outcome
Timeframe: 24 WeeksThis will be reported as the number of participants who experienced a serious advert event throughout the study.
Outcome measures
| Measure |
Intanasal Oxytocin
n=15 Participants
Cohort 1 Dosage: 0.20 IU/kg - 3 participants Cohort 2 Dosage: 0.26 IU/kg - 3 participants Cohort 3 Dosage: 0.33 IU/kg - 3 participants Cohort 4 Dosage: 0.40 IU/kg - 6 participants
|
|---|---|
|
Number of Participants With Serious Adverse Events
|
0 participants
|
SECONDARY outcome
Timeframe: 12 WeeksChildren 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 WeeksChildren 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 WeeksSocial 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.
Outcome measures
| Measure |
Intanasal Oxytocin
n=15 Participants
Cohort 1 Dosage: 0.20 IU/kg - 3 participants Cohort 2 Dosage: 0.26 IU/kg - 3 participants Cohort 3 Dosage: 0.33 IU/kg - 3 participants Cohort 4 Dosage: 0.40 IU/kg - 6 participants
|
|---|---|
|
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)
Let's Face It! Skills Battery-Matchmaker
|
-10.9 units on a scale
Interval -19.3 to -2.6
|
|
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)
Let's Face It! Skills Battery-Faces
|
-9.21 units on a scale
Interval -15.26 to -3.15
|
|
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)
Aberrant Behavior Checklist
|
3.00 units on a scale
Interval 0.05 to 5.96
|
|
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)
Social Responsiveness Scale
|
9.8 units on a scale
Interval 3.8 to 15.8
|
|
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)
Behavioral Assessment System for Children-Social
|
-2.84 units on a scale
Interval -5.31 to -0.38
|
|
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)
Behavioral Assessment System for Children-Function
|
-4.10 units on a scale
Interval -6.23 to -1.97
|
|
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)
Child Yale-Brown Obsessive-Compulsive Scale
|
2.93 units on a scale
Interval 0.95 to 4.91
|
|
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)
Repetitive Behavior Scale-Revised
|
17.3 units on a scale
Interval 6.3 to 28.3
|
|
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)
Child and Adolescent Symptom Inventory-Separation
|
7.5 units on a scale
Interval 0.2 to 14.8
|
|
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)
Let's Face It! Skills Battery-Houses
|
-10.73 units on a scale
Interval -18.5 to -2.91
|
|
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)
The Revised Eyes Test
|
-0.14 units on a scale
Interval -0.82 to 0.53
|
|
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)
Strange Stories Task
|
-1.36 units on a scale
Interval -2.72 to 0.0008
|
|
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)
Irony and Empathy Task
|
-1.64 units on a scale
Interval -3.02 to -0.27
|
|
Changes in Measures of Social Cognition, Social Function, Repetitive Behaviors, and Anxiety (Baseline to Week 12)
Child and Adolescent Symptom Inventory-General
|
11.0 units on a scale
Interval 4.0 to 18.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 WeeksSocial 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).
Outcome measures
| Measure |
Intanasal Oxytocin
n=15 Participants
Cohort 1 Dosage: 0.20 IU/kg - 3 participants Cohort 2 Dosage: 0.26 IU/kg - 3 participants Cohort 3 Dosage: 0.33 IU/kg - 3 participants Cohort 4 Dosage: 0.40 IU/kg - 6 participants
|
|---|---|
|
Measures of Social Function - The Clinical Global Impressions - Social Scale (Baseline to Week 12)
|
7 participants
|
Adverse Events
Intranasal Oxytocin
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Intranasal Oxytocin
n=15 participants at risk
Oxytocin: Intranasal Oxytocin. Please note that the Adverse Events are not presented per dose level received, as this is not a dose-finding study, it is a modified maximum tolerated dose study. This means that a small number of participants were exposed to increasing dose levels to assess for Adverse Events. It is not meaningful to analyze adverse events by cohorts due to the extremely small sample size.
|
|---|---|
|
Nervous system disorders
Emotional Lability
|
40.0%
6/15 • Number of events 7
|
|
Psychiatric disorders
Irritability
|
26.7%
4/15 • Number of events 6
|
|
Nervous system disorders
Headache
|
46.7%
7/15 • Number of events 11
|
|
Nervous system disorders
Migraine
|
6.7%
1/15 • Number of events 3
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
20.0%
3/15 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
6.7%
1/15 • Number of events 2
|
|
Infections and infestations
Upper Respiratory Infections
|
40.0%
6/15 • Number of events 7
|
|
Metabolism and nutrition disorders
Decrease Appetite
|
20.0%
3/15 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.0%
3/15 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Itchy Nose
|
6.7%
1/15 • Number of events 2
|
|
General disorders
Fatigue
|
26.7%
4/15 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Asthma Attack
|
6.7%
1/15 • Number of events 2
|
|
General disorders
Tooth Sensitivity/Pain
|
13.3%
2/15 • Number of events 2
|
Additional Information
Dr. Evdokia Anagnostou
Holland Bloorview Kids Rehabilitation Hospital
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place