Study protocol for a randomized controlled trial assessing the effectiveness and implementation of Differentiated Sickle Cell Disease Services (DSCDS) utilization for Adolescents with Sickle Cell Disease in Kampala

Background Adolescents with sickle cell disease (SCD) in urban low- and middle-income settings face significant barriers to continuous facility-based care, including high transportation costs, school disruption, long waiting times, and fragmented psychosocial support. These challenges contribute to poor retention in care and suboptimal health outcomes. Differentiated service delivery models have improved access and outcomes in other chronic conditions with similar constraints; however, their effectiveness among adolescents with SCD remains insufficiently evaluated. This study aims to assess the implementation and effectiveness of Differentiated Sickle Cell Disease Services (DSCDS) in improving health-related quality of life (HRQoL) among adolescents with SCD in Kampala, Uganda. Methods This is a two-arm, parallel, individually randomized controlled trial involving 648 adolescents aged 10–19 years receiving care at the Mulago National Referral Hospital sickle cell clinic. Participants will be randomized (1:1) to either the DSCDS intervention or standard facility-based care and followed for six months. The DSCDS intervention includes decentralized medication refills, adherence counseling, psychosocial support, and caregiver engagement delivered through monthly Community Drug Distribution Points (CDDPs). Geographic restriction will be applied to minimize contamination, and allocation will be computer-generated with concealment. The primary outcome is change in HRQoL measured using the PedsQL SCD Module, with frequency of pain crises as a key determinant. Secondary outcomes include medication adherence, retention in care, service uptake, and reduction in pain crises. Intervention exposure will be categorized by frequency of CDDP utilization. Analysis will follow the intention-to-treat principle using appropriate effect estimates with 95% confidence intervals, and adverse events will be documented throughout follow-up. Discussion This trial will provide important evidence on the effectiveness and feasibility of DSCDS in improving HRQoL among adolescents with SCD in resource-limited urban settings. The findings are expected to inform policy and guide the design and scale-up of adolescent-centered SCD service delivery models in similar contexts. Trial registration Registered with Clerk International University Research Ethics Committee CLARKE20251983, registration with the Uganda National Council for Science and Technology and the Pan African Clinical Trials Registry is underway.