Auricular Vagus Nerve Stimulation Combined with Physical Therapy for Individuals with Parkinson’s Disease: A Pilot Randomized Sham-controlled Trial

ABSTRACT Background and Purpose Both neuromodulation and physical therapy have been shown to mitigate motor and non-motor symptoms of Parkinson’s Disease. Few studies have examined the integration of noninvasive neuromodulation with physical therapy approaches for improving Parkinsonian symptoms. The purpose of this study was to investigate the safety, feasibility, and potential synergistic effects of combining transcutaneous auricular vagus nerve stimulation (taVNS) with physical therapy for enhancing the therapeutic benefits of exercise as medicine in a clinical setting. Methods This pilot study was designed as a randomized, sham-controlled clinical trial. Participants (N=20) were randomly assigned to receive active or sham-taVNS in combination with physical therapy for 12 visits over 6 weeks. We quantified safety, tolerability, and feasibility outcomes, as well as changes in cardiovascular and motor function over time. Results We observed taVNS was well tolerated without reported adverse events. Our observations further revealed taVNS administered prior to physical therapy improves cardiovascular regulation at rest and during exercise. Administering taVNS prior to exercise also led to significant and sustained improvements in motor function and balance over time. Discussion and Conclusions Combining taVNS with physical therapy was safe and tolerable. We found taVNS enhances motor improvements from physical therapy, in part, by modulating cardiovascular function during exercise. These observations support larger trials investigating the integration of taVNS into physical therapy interventions for Parkinson’s Disease. Trial Registration ClinicalTrials.gov NCT05871151 .