Transcutaneous spinal cord stimulation plus locomotor training versus sham-stimulation plus locomotor training in chronic spinal cord injury (eWALK): a multicentre, triple-blind, randomised, sham-controlled trial

Background: Although some studies have investigated the effects of transcutaneous spinal cord stimulation (tSCS), most are small, uncontrolled, and exploratory. We aimed to determine whether 12 weeks of tSCS combined with locomotor training improves walking ability (with stimulation) in people with chronic spinal cord injury (SCI) more than locomotor training alone. Methods: This international, multicentre, triple-blind, randomised sham-controlled trial (eWALK) was conducted at seven sites across Australia, USA, Scotland, and Spain. We recruited 50 community-dwelling individuals (aged ≥16 years) with chronic SCI, motor levels T1-T11 as per the International Standards for the Neurological Classification of SCI (ISNCSCI), and limited walking ability (Walking Index for SCI II (WISCI-II) levels 1-6). Participants were randomly assigned (1:1) to the stimulation or sham-stimulation group. Participants received their allocated stimulation plus locomotor training for three 30-min sessions a week for 12 weeks. Participants, assessors, and, therapists providing training were unaware of group allocation. The primary outcome was walking ability (WISCI-II) with allocated stimulation at 12 weeks. A predefined between-group difference of 2 points on the WISCI-II was set as the minimally worthwhile (ie, clinically meaningful) treatment effect. Outcomes were measured at baseline, Week 12, and, Week 16 (follow-up). Adverse events were recorded across the 12-week training period. Multiple imputation was used to impute missing values. This trial is registered with ANZCTR.org.au, ACTRN12620001241921. Findings: Between March 10, 2021, and June 14, 2024, 50 participants were enrolled and randomly allocated to study groups (stimulation group n = 25; sham-stimulation group n = 25). Data from all 50 participants were included in the primary analysis (including two dropouts). The mean between-group difference (95% CI) for walking ability with stimulation was -0.1 out of 20 on the WISCI-II (-1.6 to 1.5; p = 0.98) at 12 weeks, which did not meet the predefined clinically meaningful treatment effect of 2 points. Both groups showed improvements in walking ability with and without allocated stimulation at 12 weeks, which was maintained at 16 weeks. The number of adverse events reported was similar across groups (72 in the stimulation group, 50 in the sham group). The most frequent were skin abrasion/pressure area (n = 23), urinary incontinence (n = 11), and musculoskeletal pain (n = 10). There were no serious adverse events. Interpretation: Our findings show that 12 weeks of tSCS plus locomotor training did not improve walking for people with chronic SCI and limited walking ability, more than 12 weeks of locomotor training alone did. Future research could investigate the effects of tSCS across diverse SCI populations, such as individuals with cervical injuries, and assess its potential when combined with upper limb training or locomotor training in those with greater mobility. Funding: SpinalCure Australia, The CatWalk Trust, NHMRC Australia, and the University of New South Wales Research Infrastructure Scheme.