Efficacy of neuromuscular electrical stimulation as a therapy for sarcopenia in people on haemodialysis: study protocol for the STIM-HD randomised controlled trial

Abstract

Abstract Background Sarcopenia is highly prevalent among adults receiving haemodialysis and is associated with reduced physical function, impaired quality of life, and increased morbidity and mortality. Although structured exercise programmes can improve muscle health, most people receiving haemodialysis are unable or unwilling to participate, highlighting the need for accessible alternatives. Neuromuscular electrical stimulation (NMES) is a non-volitional method of muscle contraction that may act as an ‘exercise mimetic’. Early studies suggest benefits for muscle strength, mass, and function; however, robust evidence from adequately powered randomised trials is lacking. The STIM-HD study aims to evaluate the clinical efficacy, cost-effectiveness, and mechanistic effects of NMES in adults with sarcopenia receiving haemodialysis. Methods STIM-HD is a multi-centre, assessor-blind, randomised controlled trial that will recruit 228 adults receiving haemodialysis. Eligible participants must be receiving haemodialysis for at least 3 months, meet diagnostic criteria for handgrip strength, or prolonged sit to stand 5 performance. Participants will be randomised in a 1:1 manner to 12 weeks of NMES or 12 weeks of standard care. The intervention targets the quadriceps using a pre-defined protocol of high-frequency NMES, three times per week during routine dialysis. The primary outcome is the change in isometric muscle strength from baseline to 12 weeks. Secondary outcomes include muscle mass and architecture, physical function, body composition, physical activity, quality of life, safety, adherence, and healthcare resource use. Follow-up assessments will occur at 3, 6, and 9 months. A mechanistic outcomes sub-study will evaluate neuromuscular and molecular adaptations using electromyography, nerve stimulation, and analysis of skeletal muscle biopsies. Analyses will follow intention-to-treat principles and adjust for baseline values and minimisation factors. Discussion This study will provide a comprehensive evaluation of the efficacy of NMES to be used as a treatment for sarcopenia in patients receiving haemodialysis. By integrating functional, economic, and mechanistic outcomes, STIM-HD will generate evidence to inform whether this therapy should be adopted into routine clinical care, and offer essential insights into the biological processes underpinning molecular responses to this intervention. Trial registration ISRCTN43724916. Prospectively registered 29/11/2024.