Intranasal Oxytocin in Youth With Autism

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: Oxytocin nasal spray; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Daniel S Quintana, PhD; Phone Number: +47 22 84 50 00; Email: daniel.quintana@psykologi.uio.no

Study Locations

• Norway
  • Oslo, Norway, N-0424
    • Ullevål Hospital
    • Contact: Daniel S Quintana, PhD; Phone Number: +47 22 84 50 00; Email: daniel.quintana@psykologi.uio.no
    • Principal Investigator: Ole A Andreassen, PhD, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. Participants must be in good general physical health, as determined by the investigator.
3. Participant's pre-study physical examination and vital signs must not show any clinically significant abnormalities as determined by the investigator.
4. 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:

1. Previous nasal disease, surgery, and dependence on inhaled drugs.
2. Current significant nasal congestion due to common colds.
3. Clinically relevant history of significant hepatic, renal, endocrine, cardiac, nervous, pulmonary, haematological or metabolic disorder.
4. Systemic illness requiring treatment within 2 weeks prior to Study Day 1.
5. Full scale IQ < 70 (due to the prerequisite ability to complete self-report measures).
6. 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.
7. Known allergic reactions or hypersensitivity/intolerance to latex
8. Currently breastfeeding
9. Pregnancy (self-reported or assessed by pregnancy test prior to the first administration at Experimental session 1 and 2 for all menstruating females)
10. Participation in any (other) clinical trial with an investigational medicinal product or medical device within 3 months prior to randomisation.
11. 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.
12. Other unspecified reasons that, in the opinion of the investigator or the sponsor make the participants unsuitable for enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participation in social activities	As measured by the Participation and Environment measure-Child and Youth scale. Higher scores on the "participation frequency", "level of involvement", and "Percent total environmental supportiveness" subscores represent better outcomes, and lower scores on the "Percent never participates" and "Percent that parents desired change" represent better outcomes	Four weeks
Caregiver quality of life	As measured by the Care-related Quality of Life instrument (CarerQol). Higher scores represent better outcomes	Four weeks
Executive function	As measured by the Behavior Rating Inventory of Executive Functions. Lower scores represent better outcomes	Four weeks

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: University of Oslo
• Investigators: Principal Investigator: Ole A Andreassen, PhD, MD, University of Oslo

Study record dates

Study Major Dates

• Study Start (Estimated): September 18, 2023
• Primary Completion (Estimated): November 4, 2025
• Study Completion (Estimated): November 4, 2025

Study Registration Dates

• First Submitted: June 24, 2023
• First Submitted That Met QC Criteria: July 6, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Actual): July 7, 2023
• Last Update Submitted That Met QC Criteria: July 6, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autistic Disorder; Autism Spectrum Disorder; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: 2019-002280-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: This needs to confirmed with local data protection authorities

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No