Table 1:

Clinical trials of pharmacological interventions for people with Down síndrome

	Study type	Setting	Eligibility criteria	Investigational agent	Dosage	Primary endpoint	Result
NCT01594346	36-month randomised, double-blind, placebo-controlled phase 3 trial	Recruitment occurred at 21 sites with research experience in adults with Down syndrome in five countries (Australia, Canada, Ireland, UK, and USA)	Adults with Down syndrome aged 50 years or older (n=337)	Alpha-tocopherol (vitamin E) versus placebo	1000 international units twice per day orally	Rate of change on the Brief Praxis Test	One or more non-serious adverse event: 96% treatment group vs 93% placebo group (p=0·90). Serious adverse events (ie, medical conditions requiring hospitalisation or substantial care): 31·5% treatment group vs 32·0% placebo group (p=1·00). No between-group difference in Brief Praxis Test (generalised estimating equation: b=0·159; CI 20·732–1·049; p=0·729).
NCT01791725 (DS201)	4-week randomised, double-blind, placebo-controlled phase 2 trial	Three centres in the USA	Adults with Down syndrome without dementia (n=26)	ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6- hexol) versus placebo	250 mg once or twice per day orally	Safety and tolerability	Treatment-emergent adverse events: five (41·7%) participants in the 250 mg twice daily group, two (40·0%) in the 250 mg once daily group, and none in the placebo group. All events were mild in intensity.
NCT02738450 (3 Star)	12-month, placebo-controlled, phase 1b multicentre study plus 12-month follow-up	Four centres in the USA	Adults with Down syndrome aged 25–45 years (n=16)	ACI-24 (liposomal vaccine against aggregated β-amyloid peptides) versus placebo	Seven subcutaneous injections of 300 or 1000 μg	Safety and tolerability, antibody titre	Not yet available; a phase 2a trial is planned (NCT04373616