Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial

Summary

Background Long-term impairment of arm function following ischaemic stroke significantly impacts patients' quality of life. Recent studies suggest that pairing rehabilitation with vagus nerve stimulation (VNS) may enhance motor recovery. This randomized, triple-blind, sham-controlled trial aimed to evaluate the safety and efficacy of VNS combined with rehabilitation in improving upper limb motor function in patients with chronic stroke. Methods Conducted across 19 rehabilitation centers in the UK and USA, the trial involved participants with moderate-to-severe arm weakness, at least nine months post-ischaemic stroke. Participants were randomly assigned to receive either active VNS paired with rehabilitation or sham VNS with rehabilitation. The VNS group received stimulation parameters of 0.8 mA, 100 μs, 30 Hz, 0.5-second pulses, while the control group received 0 mA pulses. Both groups underwent six weeks of in-clinic therapy (three sessions per week) followed by a home exercise program. The primary outcome was the change in impairment, measured by the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score, assessed one day after completing in-clinic therapy. Findings and Implications A total of 108 participants were randomized (53 to the VNS group and 55 to the control group), with 106 completing the study. The VNS group showed a mean increase of 5.0 points in FMA-UE scores, while the control group showed a 2.4-point increase, resulting in a between-group difference of 2.6 points (95% CI 1.0–4.2, p=0.0014). At 90 days post-therapy, 47% of the VNS group achieved a clinically meaningful response (≥6-point improvement) on the FMA-UE, compared to 24% in the control group (p=0.0098). There was one serious adverse event related to surgery (vocal cord paresis) in the control group. These results suggest that combining VNS with rehabilitation therapy offers a promising treatment option for individuals with chronic, moderate-to-severe arm impairment following ischaemic stroke. Further research is warranted to confirm these findings and explore long-term outcomes.