Transauricular Nerve Stimulation to Enhance Exercise Capacity: Protocol for a Double-blind, Open Crossover, Randomised Sham-controlled Trial

Background: Exercise performance is a key predictor for healthy ageing. Laboratory and clinical data have shown strength of a nerve called the vagus nerve, which is lost during age-related disease processes, determines exercise performance. The investigators describe a study protocol designed to test the hypothesis that stimulation of the ear (where the vagus nerve can be safely stimulated) may improve exercise performance alongside beneficial changes in vagus nerve activity in human volunteers. Methods. 28 healthy participants aged 18-75y will be randomly allocated to electrical ear stimulation or placebo treatment for 30 minutes at the same time of day, for 7 consecutive days. Heart monitoring, exercise bike testing, a simple sit-to-stand test and blood sampling will be performed immediately before the first day's intervention and after the last day's intervention. Participants and investigators will be masked to the treatment allocations and analyses. After a 14-day break, participants will perform the same protocol for the opposite intervention to their first treatment allocation. The primary outcome will be the change in VO2Peak (the best measure of exercise performance) following stimulation or placebo protocol. Secondary outcomes include reduction in heart rate after ending the exercise bike test, reduction from peak heart rate after standing from sitting, beat-to-beat heart rate measures and blood inflammatory marker levels. These outcomes will measure exercise performance and vagus nerve function. Safety and complications of the intervention will also be recorded. The study was approved by the NHS Research Ethics Committee (21/LO/0856). Discussion. This 'first-in-man' study will explore whether non-invasive vagus nerve stimulation safely boosts exercise performance and/or vagus nerve activity using electrical ear stimulation, providing data for a device-based approach that may be broadly generalisable to improving health outcomes.