Randomised evaluation platform, interventions to treat older people with sarcopenia (REVITALiSE): protocol and description of intervention selection process

IntroductionSarcopenia is the age-related loss of muscle mass and strength. It is associated with significant adverse personal and health-economic outcomes. Despite advances in understanding the biology of muscle ageing, effective treatments remain limited. Exercise is currently the only proven intervention, but many older people are unable or unwilling to sustain the intensity of exercise required to gain results. Consequently, there is a major unmet need for new therapies. REVITALiSE is an early-phase experimental medicine platform trial designed to efficiently evaluate promising interventions in people with sarcopenia. By identifying and selecting the most promising interventions to progress to large randomised controlled trials, REVITALiSE aims to accelerate the development of effective therapies for this under-served population. Methods and analysisThe REVITALiSE platform comprises a series of parallel-group, individually randomised, controlled, open-label, proof-of-concept subtrials. Each subtrial will enrol 30 participants aged 65 years and older with probable sarcopenia, defined according to the European Working Group on Sarcopenia in Older People (EWGSOP) guidelines. The platform is designed to evaluate a range of interventions, including exercise-based approaches, device-based therapies, and nutraceuticals. Participants will be randomised in a 1:1 ratio to receive either the intervention or usual care. The primary outcome, analysed in a modified intention to treat (mITT) population, is the between-group difference in four-metre walking speed between baseline and 12-week follow-up. Secondary outcome measures specified in the master protocol include handgrip strength, the Short Physical Performance Battery (SPPB), and lean muscle mass (assessed by Dual X-ray absorptiometry). Muscle biopsies of the vastus lateralis will also be taken at baseline and follow-up. Additional mechanistic outcomes will be determined by the proposed mode of action of each intervention and specified in the relevant subtrial annex. Adverse events will be recorded for the duration of the trial. Ethics and disseminationUK Health Research Authority and Northeast - Tyne and Wear South Research Ethics Committee (IRAS 352708). Results will be made available to participants, their families, patients with sarcopenia, the public, regional and national clinical teams, and the international scientific community. Trial registration number: ISRCTN10801475 Protocol V1.0 08 May 2025 Sponsor: Newcastle Upon Tyne NHS Foundation Trust REC: NE Tyne and Wear South NHS Research Ethics Committee ref: (IRAS 352708; ref: 25/NE/0115)