Randomized controlled trial-in-progress of an interdisciplinary treatment program for youth with chronic SCD pain: Integrative strong body and mind training for sickle cell disease (I-STRONG)

Abstract

Abstract Background and Significance: Up to 20% of adolescents living with sickle cell disease (SCD) experience chronic pain (pain on most days for ≥6 months), contributing to school absences, functional disability and increased healthcare utilization. Effective chronic SCD pain management requires multicomponent treatment including individualized nonpharmacological and integrative interventions. Yet, interdisciplinary interventions designed for chronic SCD pain are not well established and lack empirical support. We previously collaborated with patient and caregiver partners to systematically adapt an existing behavioral treatment program for chronic widespread pain (cognitive-behavioral therapy for pain and integrative neuromuscular exercise training) to meet the unique needs of youth experiencing chronic SCD pain. The adapted multicomponent interdisciplinary treatment program, termed Integrative Strong Body and Mind Training (I-STRONG), was iteratively refined in a pilot trial, demonstrating high levels of feasibility, moderate to high acceptability, and safety. Over 80% of participants reported improvements in pain at post-treatment and 3-month follow-up. Pilot results and participant feedback informed further optimization of I-STRONG in preparation for a randomized controlled trial (RCT). Study Design and Methods: This multisite trial-in-progress (NCT06110754) evaluates the efficacy of I-STRONG, which integrates evidence-based mind-body, cognitive-behavioral, and neuromuscular exercise training among adolescents with chronic SCD pain, using an individually randomized group treatment design comparing Early Start (ES) to Enhanced Usual Care (EUC). The primary aim is to determine whether I-STRONG combined with standard care is more effective than standard care alone in decreasing pain intensity (primary outcome). Additional outcomes include functional and psychosocial outcomes consistent with NIH HEAL Common Data Elements (secondary outcomes) and objectively measured physical activity via actigraphy and functional walking capacity using the six-minute walk test (exploratory outcomes). Assessments are completed at pre-treatment, post-treatment, 3-month follow-up (primary endpoint), and 6-month follow-up. A subset of participants will complete a qualitative exit interview about the treatment program. I-STRONG consists of 16 group-based telehealth sessions (90 minutes each), held twice a week for 8 weeks. Caregivers are encouraged to attend at least 6 sessions. All participants can receive I-STRONG, with randomization blocks of 8-10 determining whether they begin with ES (after completing pre-treatment assessment) or EUC (approximately 8 months after the pre-treatment assessment). Study Population: Recruitment target is 155 youth-caregiver dyads across 4 pediatric SCD programs in the Midwestern, Northeastern, and Southeastern United States. Youth are eligible if they are 12-18 years old with any SCD genotype, have a stable (≥3 months) course of disease-modifying treatments as applicable, report medium or high risk for chronic pain (per Pediatric Pain Screening Tool), typical past-week pain intensity ≥4, and speak and read English. Exclusion criteria include history of co-occurring chronic pain condition unrelated to SCD, genetic or hematopoietic stem cell therapy, contraindication for participation (e.g., weight bearing restrictions), or actively receiving physical therapy, cognitive-behavioral therapy, or acupuncture for pain overlapping with active study phase. Planned Statistical Analysis: Linear mixed-effects models will evaluate changes in primary, secondary, and exploratory outcomes between ES and EUC to account for within- and between-individual variability. Primary independent variables will be study site, treatment arm, assessment timepoint, and their interaction term. Participant level random intercept, nested within group session, will be specified to model within-subject correlated outcomes and group-level clustering. Potential covariates include demographic and disease characteristics. Qualitative feedback will use coding-reliability thematic analysis from a positivist, hybrid deductive-inductive framework approach to characterize treatment impact and inform additional refinements. Progress and Impact: Enrollment is ongoing until May 2027. I-STRONG addresses a critical need for effective, multicomponent, interdisciplinary non-pharmacological treatment approaches for youth with chronic SCD pain.