Pain science education and graded sensorimotor relearning versus usual physiotherapy for chronic non-specific low back pain (RESOLVE Swiss): study protocol for a multicentre, cluster-randomised controlled trial with a nested neuroimaging substudy

Abstract Background Chronic non-specific low back pain (LBP) is the leading cause of disability worldwide and a major driver of healthcare consultations and costs also in Switzerland. In most cases the underlying cause remains unclear, and altered central nervous system processing (CNSP) has been implicated in the persistence of symptoms. A novel treatment approach - pain science education combined with graded sensorimotor relearning and loading (RESOLVE) - targets these central mechanisms within a multimodal physiotherapy programme. RESOLVE has shown clinically meaningful, long-term benefits compared with a complex sham intervention in a placebo-controlled Australian efficacy trial. Its effectiveness relative to usual physiotherapy care in real-world Swiss outpatient physiotherapy settings remains unknown. Methods This is a national, multicentre, two-arm, parallel-group, cluster-randomised, superiority trial conducted in 15 physiotherapy practices and institutions across Switzerland. Practices are randomised to deliver either the RESOLVE intervention or usual physiotherapy, each comprising up to 12 individual sessions over 16 weeks. A total of 220 adults aged 18–75 years with chronic non-specific LBP (≥ 3 months) and a Roland Morris Disability Questionnaire (RMDQ) score ≥ 7 will be recruited. The primary outcome is LBP-related disability (RMDQ) at 18 weeks post-baseline. Secondary outcomes include pain intensity, tactile acuity, movement control, medication use, workplace absence, cost-effectiveness (QALYs, ICERs), quality of life, sleep, psychological measures and goal attainment, assessed up to 52 weeks after inclusion. Data will be analysed using linear mixed models, complemented by Bayesian models accounting for clustering; a pre-specified Bayesian interim analysis will assess futility after 100 participants. An embedded neuroimaging substudy ( n = 40) will use high-resolution 7 T functional MRI to investigate intervention-related changes in sensorimotor cortical organisation and resting-state connectivity. Discussion This pragmatic, cluster-randomised trial will provide the first evidence on the real-world effectiveness and cost-effectiveness of the RESOLVE approach compared with usual physiotherapy care for chronic non-specific LBP, adapted and validated for the Swiss healthcare setting. Findings are expected to inform whether wider implementation of RESOLVE within routine Swiss physiotherapy practice is clinically and economically justified, and the embedded neuroimaging substudy will contribute insight into the CNSP underlying changes in clinical outcomes. Trial registration This trial is registered with Deutsches Register Klinischer Studien: DRKS00039237 and Human Research Switzerland: HumRes67737 and BASEC ID: 2025 − 00784.