Effects of transcutaneous auricular vagus nerve stimulation on cardiorespiratory fitness in patients with subacute stroke: a study protocol for a randomized controlled trial.

BACKGROUND: Patients with stroke often experience reduced cardiorespiratory fitness, which increases the risk of cardiovascular events, and conventional rehabilitation has limited efficacy in improving it. Transcutaneous auricular vagus nerve stimulation (taVNS) can modulate autonomic function, but its effect on cardiorespiratory fitness in stroke patients remains unclear. METHODS: This randomized controlled trial will enroll 160 patients with subacute stroke, who will be randomly assigned in a 1:1 ratio to an experimental group or a control group. Both groups will receive conventional rehabilitation training. The experimental group will additionally receive active taVNS (left auricular concha, 25 Hz, 200 µs, intensity set at or slightly above the sensory threshold, 30 min/session, 5 sessions/week for 4 weeks), while the control group will receive sham stimulation (0 mA). The primary outcome is set as peak oxygen uptake (VO2peak), assessed at baseline (T0), post-intervention (T1), and follow-up (T2). Secondary outcomes include: (1) inflammatory markers (IL-6, TNF-α); (2) neurological function (National Institutes of Health Stroke Scale, NIHSS); and (3) activities of daily living (modified Barthel Index, MBI), all measured at T0, T1, and T2. Resting-state electrocardiogram (5 min) will be recorded at T0, T1, and T2 to analyze heart rate variability (HRV) as an exploratory outcome to elucidate autonomic mechanisms, without multiplicity correction. Data will be analyzed following the intention-to-treat principle. DISCUSSION: This protocol aims to investigate the effect of taVNS on cardiorespiratory fitness in patients with subacute stroke.