Trial Outcomes & Findings for Intranasal Oxytocin in the Treatment of Autism (NCT NCT00490802)

Last Updated: 2015-10-23

Results Overview

The Clinical Global Impressions Scale - Improvement - Social is a well validated measure employing a 7-point scale of clinical global impression of improvement ( 1- very much improved, 2 - much improved, 3 - minimally improved, 4 - no change, 5 - minimally worse, 6 - much worse, 7 - very much worse) that the clinician fills out after considering all the available information on the participant including the parent history, the examination in clinic, reports from the school and other sources. Therefore the score is filtered through the judgment of the clinician evaluator. The Week 6 Improvement Ratings were used to categorize patients as clinically improved (≤2) or not (\>2). Sixteen of the 19 patients (84%) had data at Week 6. For the remaining three subjects, Week 6 ratings were imputed using expectation-maximization methods and the earlier Clinical Global Impression ratings. In all three cases the imputed ratings were \>2 and the patients were classified as not improved.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

6 Weeks

Results posted on

2015-10-23

Participant Flow

Participants were recruited through advertisements in local media. Diagnosis was established using the Diagnostic and Statistical Manual, Fourth Edition criteria for an Autism Spectrum Disorder supported by the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview - Revised performed by research-reliable administrators.

This was a randomized, double-blind, placebo-controlled, parallel design trial of intranasal oxytocin versus placebo in adults with Autism Spectrum Disorder. As such, there were no participants excluded after enrollment but prior to assignment to groups.

Participant milestones

Participant milestones
Measure	Intranasal Oxytocin Oxytocin : Intranasal Oxytocin	Placebo Placebo Comparator : Placebo Comparator
Overall Study STARTED	10	9
Overall Study COMPLETED	9	7
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Intranasal Oxytocin in the Treatment of Autism

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intranasal Oxytocin n=10 Participants Oxytocin : Intranasal Oxytocin	Placebo n=9 Participants Drug Placebo Comparator : Placebo Comparator	Total n=19 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	33.8 years STANDARD_DEVIATION 12.7 • n=5 Participants	32.9 years STANDARD_DEVIATION 14.4 • n=7 Participants	33.2 years STANDARD_DEVIATION 13.3 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	9 participants n=7 Participants	19 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 Weeks

Outcome measures

Outcome measures
Measure	Intranasal Oxytocin n=10 Participants Oxytocin : Intranasal Oxytocin	Placebo n=9 Participants Placebo Comparator : Placebo Comparator
Clinical Global Impressions Scale - Improvement - Social	3 participants	1 participants

PRIMARY outcome

Timeframe: 6 Weeks

The Repetitive Behavior Scale - Revised was developed to capture the breadth of repetitive behaviors that are specific to autism and is a parent report measure. In particular, it consists of 43-items that tap six repetitive behavior subtypes: Stereotyped, Self-injurious, Compulsive, Ritualistic, Sameness, and Restricted Interests. Two scores were calculated (higher-order vs. lower-order repetitive behaviors) in an effort to decrease the number of variables analyzed. This is based on previous factor analysis that produced these two factors: higher order (ritualistic, sameness, compulsive and restricted subscales) and lower order (stereotypy and self-injury). 1. The higher order behaviors have 29 items that can be endorsed with a maximum score of 87 and a minimum score of 0 2. The lower order behaviors have 14 items that can be endorsed, with a maximum score of 42 and a minimum score of 0 In both cases, a lower score represents a positive response.

Outcome measures

Outcome measures
Measure	Intranasal Oxytocin n=10 Participants Oxytocin : Intranasal Oxytocin	Placebo n=9 Participants Placebo Comparator : Placebo Comparator
Repetitive Behavior Scale - Revised Repetitive Behavior Scale - Revised - Higher Order	17.7 units on a scale Standard Deviation 16.2	17.8 units on a scale Standard Deviation 13.3
Repetitive Behavior Scale - Revised Repetitive Behavior Scale - Revised -Lower Order	2.4 units on a scale Standard Deviation 2.3	3.7 units on a scale Standard Deviation 2.6

PRIMARY outcome

Timeframe: 6 Weeks

The Diagnostic Analysis of Nonverbal Accuracy is a measure of emotion recognition across multiple modalities. It consists of five subtests: the Adult Facial Expression Test, the Child Facial Expression Test, the Adult Paralanguage Test, the Child Paralanguage Test, and the Adult Posture Test. The Diagnostic Analysis of Nonverbal Accuracy has established reliability and validity for children as young as 3 and adults as old as 100. The subtests of the test vary on four basic core emotions: happiness, sadness, anger, and fear, and the test provides measures of both high intensity and low intensity emotional reactions. We utilized both the Child Paralanguage and Adult Paralanguage Tests, therefore the minimum score that can be obtained is 0 and the maximum is 48. A higher score represents a positive response.

Outcome measures

Outcome measures
Measure	Intranasal Oxytocin n=10 Participants Oxytocin : Intranasal Oxytocin	Placebo n=9 Participants Placebo Comparator : Placebo Comparator
Diagnostic Analysis of Nonverbal Accuracy, Paralanguage Test	30.5 units on a scale Standard Deviation 2.7	35.2 units on a scale Standard Deviation 4.7

SECONDARY outcome

Timeframe: 6 Weeks

The Yale-Brown Obsessive-Compulsive Scale is a clinician-rated questionnaire measuring the time spent, distress, interference, resistance, and control in relation to obsessions and compulsions based on a 5-point scale. This scale has excellent reliability and validity and is used as the gold standard to measure treatment challenges in all Obsessive-Compulsive Disorder clinical trials. The Yale-Brown Obsessive-Compulsive Scale Compulsion Subscale has been shown to be a reliable and valid scale in Autism Spectrum Disorder, and in measuring change in treatment studies of autism. The minimum score that can be obtained is 0 and the maximum score is 20. A lower score represents a positive response.

Outcome measures

Outcome measures
Measure	Intranasal Oxytocin n=10 Participants Oxytocin : Intranasal Oxytocin	Placebo n=9 Participants Placebo Comparator : Placebo Comparator
Yale-Brown Obsessive-Compulsive Scale	9.4 units on a scale Standard Deviation 2.9	8.1 units on a scale Standard Deviation 2.5

SECONDARY outcome

Timeframe: 6 Weeks

The Social Responsiveness Scale has been developed to measure autism related symptoms and focuses more on social function than social cognition. The Social Responsiveness Scale has been modified for adults by and we have obtained permission to use the adult scale, although it is not commercially available yet. The Social Responsiveness Scale measures social behaviors such as social awareness, information processing, and social motivation and yields a quantitative score that has been useful in endophenotype studies of Autism Spectrum Disorder. The minimum score that can be obtained is a 0 and the maximum raw score for subscales is 66, maximum total raw score is 153. A lower score represents a positive response.

Outcome measures

Outcome measures
Measure	Intranasal Oxytocin n=10 Participants Oxytocin : Intranasal Oxytocin	Placebo n=9 Participants Placebo Comparator : Placebo Comparator
Social Responsiveness Scale	111.4 units on a scale Standard Deviation 13.5	96.5 units on a scale Standard Deviation 13.0

Adverse Events

Intranasal Oxytocin

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Intranasal Oxytocin n=10 participants at risk Oxytocin : Intranasal Oxytocin	Placebo n=9 participants at risk Drug Placebo Comparator : Placebo Comparator
Psychiatric disorders Irritability	10.0% 1/10	0.00% 0/9
Psychiatric disorders Irritability (moderate)	10.0% 1/10	0.00% 0/9
Immune system disorders Nasal congestion/allergy symptoms	20.0% 2/10	0.00% 0/9
Nervous system disorders Query absence seizures	10.0% 1/10	0.00% 0/9
General disorders Fatigue	10.0% 1/10	11.1% 1/9
Nervous system disorders Headache	10.0% 1/10	0.00% 0/9
Nervous system disorders Leg shaking	10.0% 1/10	0.00% 0/9
General disorders Increased energy	10.0% 1/10	0.00% 0/9
Psychiatric disorders Depressed mood	0.00% 0/10	11.1% 1/9
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/10	11.1% 1/9
Nervous system disorders Worsening tics	0.00% 0/10	11.1% 1/9
Psychiatric disorders Panic attack (moderate)	0.00% 0/10	11.1% 1/9

Additional Information

Dr. Evdokia Anagnostou

Holland Bloorview Kids Rehabilitation Hospital

Phone: 416-753-6005

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place