NCT01908205.

Study characteristics
Methods	12‐week trial of oxytocin versus placebo
Participants	Inclusion criteria: Male or female outpatients, 10‐17 years of age inclusive Meet DSM‐4, ADOS‐2 and ADI‐R 4 criteria for ASD CGI‐S score ≥ 4 (moderately ill) at screening Verbal and Performance scale IQ ≥ 70 (both subtests of the Wechsler Abbreviated Scale of Intelligence (WASI‐I or WASI‐II ≥ 70) if already receiving stable concomitant medications affecting behaviour, have continuous participation for 1 month prior to screening (6 weeks for fluoxetine) ‐ no changes to existing or new medication during the study if already receiving stable non‐pharmacologic educational, behavioral, and/or dietary interventions, have continuous participation during the preceding 3 months prior to screening ‐ no changes to existing or new medication during the study normal physical examination and laboratory test results at screening. able to speak and understand English participant or parents/legal guardian provides written informed consent Exclusion criteria: born prior to 35 weeks' gestational age primary psychiatric diagnosis other than ASD medical history of 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 brain MRI/structural lesion pregnant; if sexually active, female patients not on hormonal birth control or using at least two types of non‐hormonal birth control evidence or history of malignancy or any significant haematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease one or more of the following: HIV, Hepatitis B virus, Hepatitis C virus, haemophilia (bleeding problems, recent nose and brain injuries), abnormal blood pressure (hypotension or hypertension), drug abuse, immunity disorder or severe depression currently taking oxytocin or have taken intranasal oxytocin in the past with no response sensitivity to oxytocin or any components of its formulation unable to tolerate venipuncture procedures for blood sampling in foster care for whom the province/state is defined as a legal guardian Location/setting: Canada Mean IQ: not stated Mean age: all under 18 years Gender: 47 male, 7 female Sample size: 60 Reasons for dropouts/withdrawals: oxytocin 5, placebo 1 (2 LTFU, 4 withdrew) Baseline ABC‐I or other BoC scale: not an outcome Concomitant medications: details not provided Previous medications: details not provided
Interventions	Intervention (oxytocin) for 12 weeks: the proposed dosing schedule is 0.4 IU/kg oxytocin, taken twice daily, for a maximum of 24 IUs per dose for 12 weeks Comparator (placebo) for 12 weeks: the proposed dosing schedule is 0.4 IU/kg, taken twice daily, for a maximum of 24 IUs per dose for 12 weeks
Outcomes	Primary outcomes: AEs Secondary outcomes: QoL (measured using the PedsQL) (WHO 1998) tolerability Timing of outcome assessments: baseline and 12 weeks (endpoint)
Notes	Study start date: July 2013 Study end date: November 2020 Funding: details not provided Conflicts of interest: details not provided
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information. Quote: "Allocation: Randomized\"
Allocation concealment (selection bias)	Unclear risk	Insufficient information. Quote: "Allocation: Randomized"
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Only details provided were on the trials registry Quote: "Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Only details provided were on the trials registry Quote: "Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)"
Incomplete outcome data (attrition bias) All outcomes	High risk	2 LTFU, and 4 withdrew ‐ no further information
Selective reporting (reporting bias)	Unclear risk	Without a published paper or protocol it is difficult to know if all outcomes were reported
Other bias	Low risk	No other sources of bias identified