NCT01972074.

Study characteristics
Methods	12‐week trial of memantine versus placebo
Participants	Inclusion criteria: children aged 8‐17 years diagnosis of ASD according to DSM‐5 criteria, at least moderate severity of social impairment, as measured by a total raw score of ≥ 85 on the parent/guardian‐completed Social Responsiveness Scale, Second Edition (SRS‐2) and a score of ≥ 4 on the clinician‐administered ASD CGI‐S scale Exclusion criteria: IQ ≤ 70 Current treatment with lamotrigine, amantadine, N‐acetylcysteine, or D‐cycloserine Current treatment with a psychotropic medication, not listed above, on a dose that has not been stable for at least 4 weeks prior to study baseline Participants with a history of or a current liver or kidney disease Clinically unstable psychiatric conditions or judged to be at serious suicidal risk Serious, stable or unstable chronic disease such as hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischaemic heart disease), endocrinologic, neurologic, immunologic, or haneidematologic disease Location/setting: Massachusetts General Hospital. USA Mean IQ: details not provided Mean age: details not provided Gender: details not provided Sample size: memantine, 22 randomised; placebo, 21 randomised Reasons for dropouts/withdrawals: memantine, 6 did not complete (4 due to AEs, 1 lack of efficacy, and 1 withdrawal by participant); placebo, 4 did not complete (1 due to AEs, 1 LTFU, 1 lack of efficacy, and 1 withdrawal by participant). Baseline ABC‐I or other BoC scale: not an outcome Concomitant medications: details not provided Previous medications: details not provided
Interventions	Intervention (memantine) for 12 weeks: given in capsule form twice daily. It will be administered twice daily for 12 weeks (including a 4‐week titration phase to a maximum dose of 20 mg/day). Participants will undergo neuroimaging before and after the 12‐week treatment phase. Comparator (placebo) for 12 weeks: no active ingredients; given in capsule form twice daily. It will be administered twice daily for 12 weeks. Participants will undergo neuroimaging before and after the 12‐week treatment phase.
Outcomes	Primary outcomes: AEs Secondary outcomes: tolerability Timing of outcome assessments: unclear
Notes	Study start date: October 2013 Study end date: September 2019 Funding: details not provided Conflicts of interest: details not provided
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"ASD subjects will be randomized to either active memantine or placebo in a 1:1 ratio after they have been determined to meet all eligibility criteria. Randomization lists stratified by gender and racial/ethnic minority status (minority vs Caucasian) will be generated by the statistician and passed to the investigational pharmacy for assignment".
Allocation concealment (selection bias)	Unclear risk	Details not provided
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	Low risk	All randomised participants included in analyses
Selective reporting (reporting bias)	Unclear risk	It is difficult to know without a protocol
Other bias	Low risk	No other sources identified