Cross-training digital therapeutics for pediatric ADHD: study protocol for a randomized controlled trial

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) in children can result in academic and occupational failure, poor socialization, and an increased risk of accidental injuries. Digital therapeutics (DTx) leverage computers and smartphones to provide game-based treatments targeting ADHD's cognitive and behavioral aspects. Although the evidence base for DTx in ADHD is expanding, most DTx focus on a single mechanism without leveraging potential synergies between them. This study aims to evaluate the effectiveness of a cross-training DTx for children aged 6-12 with ADHD. METHODS: The DTx study is a multicenter, open-label, randomized controlled trial that employs a cross-training approach integrating neurofeedback and executive function training. A total of 210 participants will be randomly assigned to one of three groups: the medication group (MED), the DTx group (DTX), or the combination group (COM). DTX will receive home‑based digital training, MED will receive methylphenidate, and COM will receive both. The primary outcome is change in Swanson, Nolan, and Pelham Rating Scale (SNAP‑IV) total score from baseline to 8 weeks post-randomization. Non‑inferiority will be tested between DTX and MED with a non-inferiority margin of Δ = 4 points; superiority between COM and MED will be defined as the lower bound of the two‑sided 95% confidence interval for the difference being greater than 0. DISCUSSION: The clinical trial protocol presented here outlines a randomized controlled trial that evaluates DTx utilizing cross-training approach. The aim of this trial is to assess the efficacy and acceptability of the cross-training DTx for children aged 6 to 12 years with ADHD. The primary outcome is the degree of improvement in the core symptoms of ADHD (measured by SNAP‑IV). Additionally, we will evaluate compliance and potential side effects associated with the DTx. The results of this study may provide an optional non-pharmacological intervention/supplementary treatment option for children with ADHD. TRIAL REGISTRATION: NCT06369714. Registered on 17 April 2024. https://clinicaltrials.gov/study/NCT06369714.