Effects of supervised progressive resistance training on corticospinal excitability in persons with multiple sclerosis: A randomized controlled trial protocol for the NEXIMS study

BACKGROUND: Neurodegeneration is a hallmark of multiple sclerosis (MS) that affects both the structure (e.g., total or regional brain volume) and function (e.g., corticospinal excitability) of the central nervous system (CNS), driving disability progression. Consequently, lower extremity neuromuscular function and physical function are preferentially affected, ultimately contributing to a reduced quality of life. While several studies have examined the effects of resistance training (RT) and other exercise modalities on CNS structure in persons with MS (pwMS), only a few studies have evaluated changes in CNS function, even though it may adapt much more rapidly than CNS structures. To our knowledge, no previous study has examined whether progressive RT (PRT) induces changes in corticospinal excitability (CSE) for the lower extremities of pwMS. METHODS: The present randomized controlled trial (RCT) will include 66 walking-impaired pwMS, equally randomized to 10 weeks of high-dose PRT (25 supervised sessions; HIGH-PRT), low-dose PRT (10 supervised sessions; LOW-PRT), or a waitlist control (CTRL) group. The primary outcome is CSE measured by motor-evoked potential (MEP) amplitudes using Transcranial Magnetic Stimulation (TMS) of the primary motor cortex. Secondary outcomes include additional neurophysiological and neuromuscular measures, physical function, and patient-reported outcomes. ETHICS AND DISSEMINATION: This study adheres to the Helsinki Declaration and is approved by the Central Denmark Region Committees on Health Research Ethics (1-10-72-9-24). All results (positive, negative, or inconclusive) will be published in peer-reviewed scientific journals and presented at relevant scientific conferences. The www. CLINICALTRIALS: gov ID is NCT06374108.