Clinical Research Directory

Acute Cardiovascular Effects of Transcutaneous Auricular Vagus Nerve Stimulation

Introduction Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with arterial hypertension representing the most significant modifiable risk factor (Lim et al., 2012; Mills et al., 2020). While clinical manifestations of arterial hypertension typically emerge in later life, the underlying pathophysiological mechanisms, particularly autonomic dysfunction, begin decades earlier. Autonomic imbalance, characterised by sympathetic overactivity and diminished parasympathetic tone, not only precedes sustained arterial hypertension but also independently predicts future cardiovascular risk, even in normotensive individuals (He et al., 2023; Thayer et al., 2010). Reduced heart rate variability (HRV), a non-invasive marker of parasympathetic activity, has been consistently associated with increased cardiovascular morbidity across diverse populations (Task Force, 1996). Critically, young apparently healthy adults with suboptimal lifestyle factors, including physical inactivity, poor dietary habits, and chronic stress, frequently exhibit reduced HRV and altered sympathovagal balance (Liao et al., 1998). These subclinical autonomic changes represent an early, potentially reversible stage in the cardiovascular disease continuum, suggesting that interventions targeting autonomic balance may prevent or delay progression to overt disease (Goldstein et al., 2011). The vagus nerve, the main parasympathetic pathway, exerts multiple cardioprotective effects, including heart rate deceleration, baroreflex enhancement, reduced vascular tone, and anti-inflammatory activity (Thayer \& Sternberg, 2006). Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a non-invasive method to enhance vagal activity by delivering electrical stimulation to the auricular branch of the vagus nerve via surface electrodes placed on the tragus or cymba conchae (Badran et al., 2018). Neuroimaging studies confirm that taVNS activates central vagal projections, including the nucleus tractus solitarius, the primary relay station for cardiovascular autonomic control (Frangos et al., 2015). Preliminary research demonstrates that acute taVNS sessions increase HRV, enhance baroreflex sensitivity, and reduce sympathetic vascular tone in healthy adults (Clancy et al., 2014; De Couck et al., 2017), while emerging evidence suggests clinically meaningful reductions in blood pressure (BP) in hypertensive patients (Mbikyo et al., 2024). Despite these promising findings, significant knowledge gaps remain. Most studies have examined clinical populations with pre-existing autonomic abnormalities, making it difficult to isolate primary taVNS mechanisms from disease-related compensatory responses. Additionally, chronic intervention protocols preclude detailed characterisation of immediate autonomic and hemodynamic changes. Conducting mechanistic studies in healthy populations offers critical advantages: absence of confounding medications and disease adaptations enables clearer identification of taVNS-induced autonomic and hemodynamic changes, while establishing baseline response patterns provides an essential reference framework for interpreting clinical population responses and informing preventive interventions. Investigation of acute responses permits precise temporal mapping of physiological changes, distinguishing primary mechanisms from downstream consequences, enables efficient optimisation of stimulation parameters, and provides biological plausibility for chronic effects while identifying potential responders to therapy. Therefore, this study proposes a randomised, sham-controlled crossover study to systematically characterise acute cardiovascular and autonomic responses to a single 60-minute taVNS session in healthy young adults. Using continuous non-invasive BP monitoring and detailed HRV analysis, this study will establish whether taVNS produces acute, measurable changes in BP, heart rate, and autonomic balance in individuals with normal baseline function. We will elucidate the temporal dynamics of taVNS-induced effects, characterise the mechanistic pathways distinguishing cardiac, hemodynamic, and autonomic contributions, and evaluate the specificity of active stimulation versus sham conditions. By establishing baseline physiological response patterns and elucidating acute mechanisms in a well-controlled population, our findings will lay the groundwork for subsequent investigations in at-risk and hypertensive individuals, ultimately contributing to evidence-based, personalised autonomic modulation therapy for cardiovascular disease prevention and management.

Transcutaneous Auricular Vagus Nerve Stimulation and Spirometry: Sham-Controlled Randomized Trial

This study will examine the short-term effects of transcutaneous auricular vagus nerve stimulation (a non-invasive electrical stimulation delivered through the outer ear) on lung function measured by spirometry in healthy adults. The vagus nerve is involved in many automatic body functions, and ear-based stimulation has been used in research to explore its possible effects on different physiological systems. However, it is not clear whether a brief stimulation session can acutely influence breathing test results in people without respiratory disease. Healthy volunteers aged 18-40 will take part in one laboratory visit. Participants will be randomly assigned to one of two groups: (1) active bilateral stimulation applied to specific ear regions that are known to be innervated by the vagus nerve, or (2) sham stimulation using the same device setup but designed to minimize vagal activation. The stimulation session will last approximately 10 minutes. Before and after the stimulation, participants will perform standard spirometry (breathing) tests. Primary spirometric outcomes will include common measures of lung function such as forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF). Heart rate, heart rate variability, and blood pressure may also be recorded to monitor physiological responses and safety during the visit. Participation is voluntary and participants may withdraw at any time. The procedure is considered minimal risk. Possible side effects are usually mild and temporary, such as tingling, warmth, or mild discomfort at the ear. Rarely, participants may feel lightheaded; if this occurs, the procedure will be stopped and the participant will be monitored until symptoms resolve. There is no guaranteed direct benefit to participants. The results may help clarify whether short-term ear-based vagus nerve stimulation can influence spirometric parameters and may inform future studies on autonomic and respiratory interactions.

Efficacy and Safety of Transcutaneous Auricular Vagus Nerve Stimulation for Postoperative Headache Following Stent-Assisted Coiling of Unruptured Intracranial Aneurysms

The goal of this clinical trial is to evaluate the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) in reducing postoperative headache among adults undergoing stent-assisted coiling for unruptured intracranial aneurysms (UIAs). The study will include male and female participants aged 18 to 80 years who are scheduled for endovascular treatment of UIAs with stent-assisted coiling or flow diverter devices. The main questions it aims to answer are: * Can taVNS reduce the incidence of headache within 90 days after stent-assisted embolization of UIAs? * Is taVNS safe and well-tolerated in this patient population? Researchers will compare patients receiving active taVNS to those receiving sham stimulation to determine if taVNS leads to fewer postoperative headaches and reduced need for analgesic medications. Participants will: * Wear a taVNS device on the left earlobe (active group) or cymba conchae (sham group) starting 1 day before the procedure * Receive 30-minute stimulation sessions, twice daily, until postoperative day 5 * Undergo follow-up assessments of headache occurrence, pain intensity, analgesic use, and any adverse events through day 90 after the procedure

Pain Perception and the Autonomic Nervous System

In this study, we want to investigate how pain processing and sensation are related to a certain part of the nervous system, the so-called autonomic nervous system. For this purpose, we apply heat and pressure stimuli to the skin and test pain processing by means of ratings scales and sensory tests. Breathing, heart rate and sweat response are also measured. To assess the spinal cord level, we measure muscle response (measured by electromyography, EMG) to electrical stimulation. Additionally, sensory nerves will be stimulated at the ear and participants will also be given various questionnaires to complete.