The Preliminary Efficacy and Feasibility of SMILE Serious Game for Adolescents and Young Adults: Protocol for Cluster Randomized Multisite Adaptive Trial Design.

Background: Mental health problems frequently emerge during adolescence and young adulthood, yet many young people do not seek or receive timely support. Digital mental health interventions, including serious games and gamified tools, may improve accessibility and engagement, but evidence for their feasibility and preliminary efficacy across diverse European settings remains limited. Objective: This protocol describes the evaluation and trial component of the SMILE (Supporting Mental Health in Young People: Integrated Methodology for Clinical Decisions and Evidence-Based Interventions) project, which aims to evaluate the acceptability, feasibility, reach, and preliminary efficacy of a cognitive behavioral therapy (CBT)-informed gamified mobile intervention for adolescents and young adults, and to explore mechanisms of change and the impact of its implementation contexts. Methods: SMILE uses a cluster-randomized, multisite, multiarm adaptive proof-of-concept design across 7 European countries, complemented by semistructured stakeholder interviews. Adolescents and young adults aged 10-24 years are recruited mainly through schools, universities, and community channels; the target sample is 1438 participants. Clusters are assigned to 1 of 3 sequences comprising a neutral baseline period followed by 2, 4, or 5 game modules, and are randomized to a feedback or no-feedback version of the intervention. The intervention consists of the SMILE Game App (Nurogames and DigitalTwin Technology) and Companion App (RDIUP), which deliver CBT-based gamified content, self-monitoring, experience sampling, and, in one of the study conditions, automated personalized feedback. Primary outcomes are anxiety and depression. Secondary outcomes include well-being, resilience, emotion regulation, self-efficacy, and social anxiety. Feasibility, acceptability, engagement, app usage, in-game metrics, and diary-based digital markers are also assessed. Quantitative data will be analyzed using linear mixed-effects models with adaptive interim analyses. Qualitative stakeholder interviews with young people, their legal guardians, school professionals, and clinicians will be analyzed using inductive thematic analysis within a mixed-methods realist evaluation framework. Results: The proof-of-concept trial was prospectively registered on April 29, 2025 (ISRCTN32523126). Study rollout is taking place from September 2025 to June 2026. As of March 2026, recruitment is ongoing, 2 study sequences have been completed, and the third sequence began at the end of March 2026. Primary results are expected in September 2026. Conclusions: SMILE is designed to generate evidence on the feasibility, acceptability, and preliminary efficacy of a scalable gamified mental health intervention for young people across diverse European contexts. The findings will inform intervention refinement, evaluation of the added value of personalized feedback, and the design of a future definitive randomized controlled trial and broader implementation in educational and clinical settings.