PROJECT SUMMARY/ABSTRACT Adolescent idiopathic scoliosis (AIS) is a spinal deformity of unknown etiology, resulting in rotation and abnormal curvature. Associated physical signs include uneven shoulders and waist, rib and flank protrusions, as well as hip misalignment. Scoliosis also affects psychological wellbeing, and can cause cardio-respiratory issues, pain, discomfort and disability in older ages. AIS is a relatively common pediatric musculoskeletal condition, affecting 0.5%–5.2% of adolescents. Females are disproportionally affected, with a female-to-male ratio of 10:1 in curves larger than 50°. Scoliosis progression can accelerate rapidly over a short period of time, particularly during growth spurts. The most common treatment for AIS is observation (“watchful waiting”) for children with curves between 10°–25°, bracing for curves 25°–45°, and surgery typically recommended for growing children with curves >45°. Every year in the USA there are ~29,000 scoliosis surgeries, each costing ~$92,000 USD. Surgery is irreversible and comes with risk of blood loss, infection, neurological compromise, or pseudarthrosis that requires reoperation. Recent studies demonstrate great promise for specialized physiotherapeutic scoliosis specific exercise (PSSE), such as “Schroth” therapy, for decelerating or preventing progression, and improving outcomes. There is a crucial need for expanding the related evidence base, through a rigorous and adequately powered multi-center randomized controlled trial (RCT). The proposed project will lead to development of such a trial, with preparation and submission of a corresponding U01 application to fund the RCT conduct. Our overarching hypothesis is that scoliosis-specific physical therapy in skeletally immature children with mild and moderate scoliosis (curves <45°) will reduce risk of scoliosis progression, improve patient reported outcomes, and in long-term follow-up will reduce the risk of requiring surgery. To develop our plan, we propose two aims: (1) Design a rigorous clinical trial protocol for evaluation of a scoliosis-specific physical therapy intervention in AIS; (2) Complete several milestones as the basis for preparation of a successful U01 application, including development of a manual of operating procedures, design and testing of case report forms and electronic data capture systems, selection of study sites and investigators, development and testing of recruitment procedures, IRB and regulatory document preparation, and development of a Data Safety Monitoring Plan. This will lay the groundwork for a landmark trial for non- operative management of AIS, with potential to impact standard of care for the most common pediatric spinal disorder.