Intranasal Oxytocin in Youth With Autism

Study Overview
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Brief Summary
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Growing evidence demonstrates the critical contribution of the neuropeptide oxytocin in the development and maintenance of autism, due to its role in social behaviour and learning processes. While some preliminary findings in oxytocin administration trials have been promising, a complete understanding of the effects of long-term oxytocin administration in autism remains elusive, as participant numbers in oxytocin administration studies in autism have been small, most studies exclusively recruit males, and reproducibility has been inconsistent. To address this critical knowledge gap, this project will include a double-blind, placebo-controlled, randomized controlled crossover trial of a four-week intranasal oxytocin treatment (24 international units, twice-daily) in 128 male and female youth with ASD aged 12-20, with social and repetitive behaviors as primary outcome measures. The investigators predict that intranasal oxytocin treatments will increase performance on social behavior measures and reduce repetitive behaviors using caregiver-reported measures. Along with the investigation of oxytocin's long-term effects, the investigators will also assess the impact of oxytocin administration on computer-based laboratory tasks that can precisely measure how participants process social cues and disengage with repetitive behaviours. In addition, an electrocardiogram will be collected to evaluate the impact of oxytocin administration on parasympathetic nervous system activity.

Official Title
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A Randomized, Placebo-controlled, Double-blind, 2-period Cross-over Study in Youth With Autism Spectrum Disorders Evaluating Social and Repetitive Behaviors After Four Weeks of Twice Daily-doses of 24IU of Intranasally Administered Oxytocin

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Oxytocin nasal spray
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants between the ages of 12 and 20, both inclusive, with a confirmed diagnosis of autism spectrum disorder (ASD) diagnosis as per the ADOS/ADI. Participants must be in good general physical health, as determined by the investigator. Participant's pre-study physical examination and vital signs must not show any clinically significant abnormalities as determined by the investigator. Participants and caregivers must be able to communicate well with the investigator, to understand and comply with the requirements of the study, and to understand the oral and written study information Exclusion Criteria: Previous nasal disease, surgery, and dependence on inhaled drugs. Current significant nasal congestion due to common colds. Clinically relevant history of significant hepatic, renal, endocrine, cardiac, nervous, pulmonary, haematological or metabolic disorder. Systemic illness requiring treatment within 2 weeks prior to Study Day 1. Full scale IQ < 70 (due to the prerequisite ability to complete self-report measures). Known allergic reactions or hypersensitivity to any component of the study medication in the nasal spray, such as propyl parahydroxybenzoate (E216), methyl parahydroxybenzoate (E218) and chlorobutanol hemihydrate. Known allergic reactions or hypersensitivity/intolerance to latex Currently breastfeeding Pregnancy (self-reported or assessed by pregnancy test prior to the first administration at Experimental session 1 and 2 for all menstruating females) Participation in any (other) clinical trial with an investigational medicinal product or medical device within 3 months prior to randomisation. New concomitant medications or formal cognitive/behavioral therapies. If a participant has been taking any medications or receiving formal cognitive/behavioral therapies for at least 4 weeks, then this is not considered a new therapy. Other unspecified reasons that, in the opinion of the investigator or the sponsor make the participants unsuitable for enrolment.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxytocin<br>24IU oxytocin liquid delivered with a pump-actuated nasal spray device, administered twice-daily | Drug: Oxytocin nasal spray<br>* 24IU oxytocin liquid delivered with a pump-actuated nasal spray device, administered twice-daily<br>|
| Placebo Comparator: Placebo<br>Placebo delivered with a pump-actuated nasal spray device, administered twice-daily | Drug: Placebo<br>* Placebo liquid nasal spray administered twice-daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Social behavior | Assessed by the total score of the Social Responsiveness Scale-Second Edition (SRS-2), as completed by caregivers of the participants. Lower scores represent better outcomes. | Four weeks | 
| Repetitive behaviour | Assessed with the Repetitive Behavior Scale-Revised (RBS-R), as completed by caregivers of the participants. Lower scores represent better outcomes. | Four weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Behavioral inflexibility | Assessed by the Behavioral inflexibility scale (BIS), completed by caregivers of the participants. Lower scores represent better outcomes. | Four weeks | 
| Social cognition | Assessed by a computerized Emotional body language task completed by the participants. Higher accuracy scores represent better outcomes. | Four weeks | 
| Repetitive cognition | Assessed by a computerised probabilistic reversal learning task completed by participants. More regressive errors represent worse outcomes (i.e., after initially choosing the new correct response, participants regress back to choosing the previously rewarded response) | Four weeks | 
| Vagally-mediated heart rate variability | Calculated using electrocardiogram (RMSSD and High Frequency HRV) | Four weeks |