PROJECT SUMMARY Sickle cell disease (SCD), the most common life-shortening genetic disorder, affects primarily Black youth in the United States. SCD has its first health impact in infancy, but more severe complications (e.g., organ damage, chronic pain, risk for early mortality) emerge in adolescence. Further, these racialized youth face social determinants of health (SDOH)-related barriers (e.g., discrimination, access to care, financial hardship) that may impact their access to care, resulting in missed opportunities to prevent complications and a higher risk for disease progression. Effective disease self-management is essential to improving care and outcomes and lowering healthcare costs for adolescents and young adults (AYA) with SCD. However, there is limited research available describing the specific factors that need to be addressed to improve self-management and health outcomes for these youth. Our multidisciplinary team used a socioecological framework to develop a novel ehealth self-management intervention for AYA with SCD called SCThrive. SCThrive combines group sessions with a therapist with a companion mobile app. Our pilot work demonstrated improved patient activation (knowledge, skills, and self-efficacy) and self-management behaviors in AYA with SCD compared to a control condition. In addition, those who use the app more frequently showed more improvements. Older AYA used the app less and reported more SDOH-related barriers to self-management. Thus, we will maximize the clinical benefit of SCThrive by 1) adding app engagement strategies for older AYA, 2) conducting a more systematic assessment of SDOH-related barriers, and 3) integrating ways to address these barriers into the intervention. The objective of this proposed project is to conduct a randomized controlled trial (RCT) with adolescents with SCD across four SCD centers. Our aims are to examine the impact of SCThrive on patient activation (primary outcome; Aim 1) and self-management behaviors, functional disability, health-related quality of life, and emergency room visits (secondary outcomes) at post-treatment and follow-up (Aim 2). We hypothesize that adolescents randomized to SCThrive will have greater improvement in patient activation (primary outcome) compared to those randomized to standard care (control condition). We will also explore the relationship between SDOH-related barriers (e.g., stigma, access to care) and treatment response (i.e., patient activation and self-management behaviors). The team has expertise in SCD, patient activation, behavioral interventions, ehealth/mhealth, adherence and self-management, health equity, RCT and statistical analyses and has collaborated on pediatric SCD intervention studies that lay the foundation for this proposal. The study is significant because it addresses the need for targeted, culturally tailored interventions to improve self- management in adolescents with SCD. The proposed research is innovative because it integrate...