Bumetanide for the Autism Spectrum Clinical Effectiveness Trial

This is a multicenter, double-blind, randomized, placebo-controlled trial testing the effectiveness of three months bumetanide treatment in 172 children aged 5 to 15 years with ASD, with or without epilepsy. The primary endpoint is change in the ABC-I scale at Day 91. Usual care + bumetanide will be compared with usual care + placebo. Participants will be included in Groningen and Utrecht (the Netherlands).

To confirm that twelve weeks of add-on treatment with bumetanide will improve daily life functioning and reduce behavioral symptoms related to hyperexcitability in children and adolescents with autism spectrum disorder and/or epilepsy.

Pre-treatment and screening (D-30 to Day0)

o Screening for eligibility

o Baseline measurements (all primary and secondary outcomes, except iPCQ and TiC-P)

Treatment (D0 to D91)

o Blood analysis at D4, D7, D14, D28, D56

o End of treatment outcome measurements D91 (all primary and secondary outcomes)
Washout (D91 to D119)

o End of washout outcome measurements D119 (all primary and secondary outcomes, except iPCQ and TiC-P)

The investigational product (IP) consists of bumetanide 0.5 mg tablets or placebo, which will be provided as an add-on treatment, supplementary to the regular use of AEDs or other (allowed) comedications. Dose reductions to manage side effects will be allowed at any time. Due to the expected chance of frequent mild to moderate hypokalemia, all subjects will receive standard potassium supplementation during the 91 days of treatment. The treatment period will be followed by a wash-out period to evaluate return of symptomatology and reversibility of treatment effect.



Placebo product will be administered as comparator of the Bumetanide in exact similar tablets. The qualitative and quantitative composition in excipients of the Placebo product is comparable to that of Bumetanide 0.5 mg tablets.