PROJECT SUMMARY Chronic pain in pediatric sickle cell disease (SCD) is a major clinical challenge due to the complex interaction of biological, psychological, and social factors. Consequently, current pharmacological and non-pharmacological treatments have variable and limited effectiveness resulting in the persistence of chronic pain during adolescence into adulthood. Optimal treatment of chronic SCD pain requires an individualized, interdisciplinary care approach that targets multifaceted biopsychosocial factors and common psychological comorbidities, such as pain-related anxiety, fear of movement, and depression, that maintain chronic pain and functional impairment. The objectives of the proposed research are to partner with patient and family stakeholders to adapt and refine an existing mind-body, cognitive-behavioral, and neuromuscular movement treatment (Fibromyalgia Integrative Training for Teens, FIT Teens) to target the unique needs and preferences of families managing chronic pain in SCD (R61 phase) and conduct a randomized clinical trial to evaluate the effectiveness of the new adapted intervention (termed I-STRONG for SCD) among youth with chronic SCD pain (R33 phase). The aims of the proposed study are to: 1) adapt and refine the FIT Teens intervention to develop a new culturally tailored I- STRONG intervention for youth with chronic SCD pain (R61 phase), 2) optimize the feasibility and acceptability of I-STRONG for SCD (R61 phase), and 3) conduct a multi-site randomized clinical trial to evaluate initial effectiveness of I-STRONG for SCD (R33 phase). We will conduct mixed method approaches to collect qualitative feedback informed by patient and family lived experiences regarding intervention content, format, perceived benefits, and barriers/facilitators to engagement with youth who have chronic SCD pain and their parents. Community stakeholder advisory boards and iterative design will inform intervention adaptation and refinement to enhance clinical implementation. We hypothesize that patients receiving I-STRONG will demonstrate significant reduction in pain interference and pain intensity (primary outcomes), and significant improvements in depressive symptoms, pain-related fear of movement, and health-related quality of life (secondary outcomes), and objectively measured physical activity (exploratory outcomes) at 3-month follow-up (primary endpoint) and 6-month follow-up. Our long-term goal is to optimize chronic SCD pain management through a multicomponent integrative approach that will be scalable for broad dissemination.