ObjectivePreliminary evidence suggests that omega-3 fatty acids may reduce hyperactivity in children with autism spectrum disorder (ASD). We sought to examine the feasibility of a novel, Internet-based clinical trial design to evaluate the efficacy of this supplement. MethodE-mail invitations were sent to parents of children aged 5 to 8 years enrolled in the Interactive Autism Network. All study procedures, including screening, informed consent, and collection of outcome measures took place over the Internet. The primary outcome measures were parent- and teacher-rated changes in hyperactivity on the Aberrant Behavior Checklist. ResultsDuring the 6-week recruitment period, 57 children from 28 states satisfied all eligibility criteria and were randomly assigned to 1.3 grams of omega-3 fatty acids or an identical placebo daily for 6 weeks. Outcome assessments were obtained from all 57 participants and 57 teachers, and the study was completed in 3 months. Children in the omega-3 fatty acid group had a greater reduction in hyperactivity (−5.3 points) compared to the placebo group (−2.6 points), but the difference was not statistically significant (1.9-point greater improvement in the omega-3 group, 95% CI = −2.2 to 5.2). Side effects were rare and not associated with omega-3 fatty acids. Participant feedback was positive. ConclusionInternet-based, randomized controlled trials of therapies in children with ASD are feasible and may lead to marked reductions in the time and cost of completing trials. A larger sample size is required to definitively determine the efficacy of omega-3 fatty acids.Clinical trial registration information—Omega-3 Fatty Acids for Hyperactivity Treatment in Autism Spectrum Disorder; http://clinicaltrials.gov; NCT 01694667.