Auricular Vagus Research Articles

Efficacy of Vagal nerve stimulation on anxiety among elderly retired teachers during COVID-19 pandemic.

Excessive fear, worry and behavioral disturbances define anxiety, with particular significance attributed to vagal nerve, a crucial transmitter of information to the brain regions governing anxiety. Highlighting the importance of vagal nerve, transcutaneous auricular vagal nerve stimulation (TaVNS) emerges as a tolerable and safe technique. The success of non-invasive vagal nerve stimulation in alleviating anxiety underscores the pivotal role of the vagal nerve. The purpose of this study was to assess the effectiveness of physiotherapy interventions in mitigating anxiety among retired teachers during the COVID-19 pandemic, emphasizing the relevance of targeting the vagal nerve for improved mental well-being. 60 retired teachers diagnosed with anxiety were chosen through random allocation. Participants were divided into two groups: Group A (Experimental group) received transcutaneous auricular vagal nerve stimulation (TaVNS), and Group B (Control group) underwent the Jacobson relaxation technique. Intervention period spanned 4 weeks, with four sessions per week, lasting 30 minutes. The outcome measures included Generalized Anxiety Disorder-7 (GAD-7) questionnaire and salivary cortisol levels. Following the 4-week intervention, both groups exhibited a significant reduction in Generalized Anxiety Disorder-7 (GAD-7) scores and salivary cortisol levels (P < 0.001). Notably, Group A demonstrated a significantly higher effectiveness rate compared to Group B. The study concludes that transcutaneous auricular vagal nerve stimulation (TaVNS) is effective in reducing anxiety among retired teachers. Transcutaneous auricular vagal nerve stimulation (TaVNS) proves to be a powerful and effective intervention in alleviating anxiety among retired teachers, emphasizing its potential significance in enhancing mental well-being.

Genetic labeling of the nucleus of tractus solitarius neurons associated with electrical stimulation of the cervical or auricular vagus nerve in mice

IntroductionVagus nerve stimulation (VNS) is clinically useful for treating epilepsy, depression, and chronic pain. Currently, cervical VNS (cVNS) treatment is well-established, while auricular VNS (aVNS) is under development. Vagal stimulation regulates functions in diverse brain regions; therefore, it is critical to better understand how electrically-evoked vagal inputs following cVNS and aVNS engage with different brain regions. ObjectiveAs vagus inputs are predominantly transmitted to the nucleus of tractus solitarius (NTS), we directly compared the activation of NTS neurons by cVNS or aVNS and the brain regions directly projected by the activated NTS neurons in mice. MethodsWe adopted the targeted recombination in active populations method, which allows for the activity-dependent, tamoxifen-inducible expression of mCherry—a reporter protein—in neurons specifically associated with cVNS or aVNS. ResultscVNS and aVNS induced comparable bilateral mCherry expressions in neurons within the NTS, especially in its caudal section (cNTS). However, the numbers of mCherry-expressing neurons within different subdivisions of cNTS was distinctive. In both cVNS and aVNS, anterogradely labeled mCherry-expressing axonal terminals were similarly observed across different areas of the forebrain, midbrain, and hindbrain. These terminals were enriched in the rostral ventromedial medulla, parabrachial nucleus, periaqueductal gray, thalamic nuclei, central amygdala, and the hypothalamus. Sex difference of cVNS- and aVNS-induced labeling of NTS neurons was modest. ConclusionThe central projections of mCherry-expressing cNTS terminals are comparable between aVNS and cVNS, suggesting that cVNS and aVNS activate distinct but largely overlapping projections into the brain through the cNTS.

Effect of vagus nerve stimulation (taVNS) on anxiety and sleep disturbances among elderly health care workers in the post COVID-19 pandemic.

Healthcare workers (HCWs) have been significantly impacted by the pandemic. Elderly health care workers carry out a variety of duties at work and have years of clinical expertise. Anxiety and insomnia are among the more commonly encountered problems in senior physicians and other geriatric medical professional populations. The study aims to determine the effect of vagal nerve stimulation on anxiety and sleep disturbances among geriatric medical professionals. 42 participants were enrolled in this study based on the inclusion and exclusion criteria. The participants were divided into two groups using the closed envelope approach, and they took part in therapy sessions lasting 30 minutes, three times per week for a period of four weeks. The Experimental group A received non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) and Control group A received Jacobson's progressive muscle relaxation technique. With a p value of 0.001, taVNS stimulation significantly improved sleep quality and reduced anxiety after 4 weeks. The post-intervention assessment revealed a highly significant improvement in Group A, with a T value of 251 (p < 0.001). The findings suggest that taVNS may be an effective intervention for addressing anxiety and sleep issues in geriatric medical professionals. These results contribute to the exploration of non-invasive strategies to enhance the well-being of healthcare professionals working in demanding environments.

Transcutaneous auricular vagal nerve stimulation for consciousness recovery in patients with prolonged disorders of consciousness (TAVREC): study protocol for a multicenter, triple-blind, randomized controlled trial in China

IntroductionProlonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and...

Transcutaneous Auricular Vagal Nerve Stimulation in Healthy Non-Sedated Horses: A Feasibility Study.

This study aimed to evaluate the feasibility of transcutaneous auricular vagal nerve stimulation (tAVNS) in healthy horses and its effect on heart rate variability (HRV). The study comprised three phases: the selection of mares, their acclimatization to the tAVNS, and the stimulation phase. Stimulation was performed with two electrodes positioned on the right pinna. The settings were 0.5 mA, 250 μs, and 25 Hz for pulse amplitude, pulse width, and pulse frequency, respectively. HRV was analysed before (B1), during (T), and after (B2) the tAVNS. From the 44 mares initially included, only 7 completed the three phases. In these mares, the heart rate (HR) was significantly lower, and frequency domain parameters showed an increased parasympathetic tone in B2 compared with B1. However, in 3/7 mares, the HR was significantly higher during T compared with B1 and B2, compatible with a decreased parasympathetic tone, while in 4/7 mares, the HR was significantly lower and the parasympathetic nervous system index was significantly higher during T and B2 compared with B1. The tAVNS is an economical and easy procedure to perform and has the potential to stimulate vagal activity; however, it was poorly tolerated in the mares included in this study.

Pairing taVNS and CIMT is feasible and may improve upper extremity function in infants.

In this study we combined non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) with 40 h of constraint induced movement therapy (CIMT) in infants. All infants completed the full intervention with no adverse events. Therapists were able to maintain high treatment fidelity and reported high ratings for ease of use and child tolerance. Preliminary results show promising gains on motor outcomes: Mean QUEST increase 19.17 (minimal clinically important difference, MCID 4.89); Mean GMFM increase 13.33 (MCID 1%-3%). Infants also exceeded expectations on Goal Attainment Scores (+1). Early data is promising that taVNS paired with intensive motor CIMT is feasible, reliable, and safe in young infants with hemiplegia, and may help harness activity-dependent plasticity to enhance functional movement.

Effect of Vagal Nerve Stimulation on Anxiety and Sleep Disturbances among Geriatric Population: A Pilot Study

Background: Anxiety during the COVID-19 pandemic has been a significant concern for people of all age groups,including geriatric individuals. The elderly population has faced unique challenges during this time, which cancontribute to increased anxiety levels. The uncertainty and fear surrounding the pandemic can lead to increasedanxiety and stress, which can negatively impact sleep quality and duration.Purpose: The aim of this study is to find out the effect of vagal nerve stimulation on anxiety and sleep disturbancesamong geriatric population.Methodology: Using the Purposive Sampling method, a total of 20 individuals were chosen based on the inclusionand exclusion criteria. The participants were divided into two groups using the closed envelope method, and theytook part in therapy sessions lasting 30 minutes, three times per week for a period of four weeks. The control groupreceived Jacobson’s progressive relaxation technique, whereas the experimental group received non-invasiveTranscutaneous auricular vagal nerve stimulation.Result: With a p value of 0.001, transcutaneous auricular vagal nerve activation significantly improved sleepquality and reduced anxiety after 4 weeks.Conclusion: Study showed that transcutaneous vagal nerve stimulation was effective in reducing Anxiety andimproving sleep quality in geriatric population.

Effect of Vagal Nerve Stimulation on Swallowing in Subjects with Post Stroke Dysphagia

Background: The study was developed to find the effect of auricular transcutaneous vagal nerve stimulation ondifficulty in swallowing in post stroke dysphagia.Purpose: The purpose of this research is to extensively investigate and analyse how VNS impacts swallowing inpeople with post-stroke dysphagia.Materials and Methods: A total, 30 individuals have been selected mainly according to the criteria of both theinclusion and exclusion, from the above-mentioned study setting. The study was explained to subjects and writtenconsent was collected from all subjects prior to the initiation of procedure. The subjects included the study wasrandomly allocated into 2 groups The participants in group A will receive Transcutaneous auricular vagal nervestimulation, which is given for 20 min with the frequency of about 25 Hz, amplitude: 1 mA, pulse width: 360μs using clip electrode being placed in Cymba Concha, along with the conventional exercises and Group B willreceive Neuromuscular electrical stimulation will be given as Interrupted direct current at 30 Hz for 100ms, andthe intensity was increased until perceptible visible contraction.Results: Auricular transcutaneous vagal nerve stimulation showed a significant effect in improving swallowingfunctions at 4 weeks, with a p value which is &lt; 0.001.Conclusion: This study showed that the transcutaneous auricular vagal nerve stimulation showed a positive effectin improving swallowing functions in patients with dysphagia.

Effectiveness of Vagal Nerve Stimulation on Obsessive Compulsive Disorder Among Post Covid-19 Infected Individuals

Background: COVID-19 has impacted everyday life and many people are affected by it. Regular Hand washing,maintaining hygiene, avoiding handshaking &amp; face-to-face interaction, social distancing, quarantine areprecautionary measures which result in rapidly increasing depression and anxiety among common populationand it results in OCD.Purpose: This study aims to investigate the effectiveness of vagal nerve stimulation on obsessive compulsivedisorder among post-covid 19 infected individuals.Methodology: A total of 20 participants was selected using the Purposive sampling technique based on theinclusion and exclusion criteria. Then, the participants were allocated into 2 groups by closed envelope methodand the participants in the control group receive cognitive behavioural therapy for 30 minutes, 4 sessions/weekfor 4 weeks. The experimental group receive Transcutaneous auricular vagal nerve stimulation. The stimulationwas given for 30 minutes,4sessions/week along with CBT.Result: With a p value of 0.001, transcutaneous auricular vagal nerve activation significantly reduced obsessivecompulsive disorder symptoms after 4weeks in experimental group.Conclusion: The Study showed that transcutaneous auricular vagal nerve stimulation was effective in reducingsymptoms of OCD among post covid-19 infected individuals.

Effect of Vagal Nerve Stimulation on Cognitive Impairment Among Subjects with Anterior Cerebral Artery Syndrome: A Pilot Study

Background: Cognitive dysfunction, including impairments in attention, memory, executive function, andprocessing speed. This study was developed to determine the effectiveness of transcutaneous auricular vagalnerve stimulation on cognitive impairment among subjects with anterior cerebral artery syndrome.Purpose: The purpose of the study is to compare and evaluate the effectiveness of two non-pharmacologicalmethods of treatment for cognitive impairment patients with ACA syndrome.Material and Methods: The project was conducted as a pilot study in a private hospital in Chennai. Theexperimental group (group A) received transcutaneous auricular vagal nerve stimulation for 20 minutes andconventional strengthening exercises for the affected limb for 10 minutes. Group B got conventional cognitivetraining (20 minutes) and strengthening exercises (10 minutes). Following the four-week treatment, a post-testanalysis was performed using the Montreal cognitive assessment scale.Results: The post-test analysis obtained a mean value of about 27.25 and SD 1.5 for group A, whereas group Brevealed 22.75 ± 1.25, mean ± SD, and a significant P value of 0.004.Conclusion: Non-invasive transcutaneous auricular vagal nerve stimulation has been proven to be an effectiveapproach for preventing vascular dementia.

Use of non-invasive transcutaneous auricular vagus nerve stimulation: neurodevelopmental and sensory follow-up.

To assess the impact of non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) paired with oral feeding on long-term neurodevelopmental and sensory outcomes. We tested 21 of 35 children who as infants were gastrostomy tube (G-tube) candidates and participated in the novel, open-label trial of taVNS paired with oral feeding. To evaluate possible effects on development at 18-months after infant taVNS, we performed the Bayley-III (n = 10) and Sensory Profile (SP-2, n = 12) assessments before the COVID pandemic, and Cognitive Adaptive Test (CAT), Clinical Linguistics and Auditory Milestone (CLAMS), Ages and Stages Questionnaire (ASQ), and Peabody Developmental Motor Scales-2 gross motor tests as possible during and after the pandemic. We compared outcomes for infants who attained full oral feeds during taVNS ('responders') or received G-tubes ('non-responders'). At a mean of 19-months, taVNS 'responders' showed significantly better general sensory processing on the SP-2 than 'non-responders'. There were no differences in other test scores, which were similar to published outcomes for infants who required G-tubes. This is the first report of neurodevelopmental follow-up in infants who received taVNS-paired feeding. They had similar developmental outcomes as historical control infants failing oral feeds who received G-tubes. Our data suggests that infants who attained full oral feeds had better sensory processing.

Transcutaneous Auricular Vagal Nerve Stimulation Is Effective for the Treatment of Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

Vagal nerve stimulation (VNS) can be used to modulate gastrointestinal motility, inflammation, and nociception. However, it remains unclear whether VNS is effective in adult patients with functional dyspepsia (FD). We investigated the effectiveness of transcutaneous auricular VNS (taVNS) in patients with FD. Consecutive patients with FD meeting Rome IV criteria with modified FD Symptom Diary score ≥10 were enrolled. Patients were randomly allocated to 10-Hz taVNS (V10 group), 25-Hz taVNS (V25 group), or sham group, with 30 minutes of treatment twice a day for 4 weeks. The primary outcome was the response rate at week 4, defined as the proportion of patients whose modified FD Symptom Diary score was reduced ≥5 when compared with the baseline. Secondary outcomes included adequate relief rate and adverse events. A total of 300 patients were randomized to V10 (n = 101), V25 (n = 99), and sham groups (n = 100). After 4 weeks of treatment, V10 and V25 groups had a higher response rate (81.2% vs 75.9% vs 47%, both P < 0.001) and adequate relief rate (85.1% vs 80.8% vs 67%, both P < 0.05) compared with the sham group. There was no significant difference between V10 and V25 in response rate and adequate relief rate (both P > 0.05). The efficacy of taVNS (both 10 and 25 Hz) lasted at week 8 and week 12 during follow-up period. Adverse events were all mild and comparable among the 3 groups (1%-3%). Our study firstly showed that 4-week taVNS (both 10 and 25 Hz) was effective and safe for the treatment of adult FD ( clinicaltrials.gov number: NCT04668534).

The Effect of taVNS on the Cerebello-Thalamo-Cortical Pathway: a TMS Study

fMRI studies show activation of cerebellum during transcutaneous auricular vagal nerve stimulation (taVNS); however, there is no evidence whether taVNS induced activation of the cerebellum translates to the cerebellar closed loops involved in motor functions. We assessed the propensity of taVNS at 25 Hz (taVNS25) and 100 Hz (taVNS100) to modulate cerebello-thalamo-cortical pathways using transcranial magnetic stimulation. In our double blind within-subjects study thirty-two participants completed one visit during which cerebellar brain inhibition (CBI) was assessed at baseline (no stimulation) and in a randomized order during taVNS100, taVNS25, and sham taVNS (xVNS). Generalized linear mixed models with gamma distribution were built to assess the effect of taVNS on CBI. The estimated marginal means of linear trends during each taVNS condition were computed and compared in a pairwise fashion with Benjamini-Hochberg correction for multiple comparisons. CBI significantly increased during taVNS100 compared to taVNS25 and xVNS (p = 0.0003 and p = 0.0465, respectively). The taVNS current intensity and CBI conditioning stimulus intensity had no significant effect on CBI. taVNS has a frequency dependent propensity to modulate the cerebello-thalamo-cortical pathway. The cerebellum participates in closed-loop circuits involved in motor, cognitive, and affective operations and may serve as an entry for modulating effects of taVNS.

Transcutaneous auricular branch vagal nerve stimulation as a non-invasive add-on therapeutic approach for pain in systemic sclerosis

ObjectiveSystemic sclerosis (SSc) is an autoimmune disease with health-related quality of life (HRQoL) high impairment. Pain is of paramount importance to be targeted by therapeutical approaches. Our study aim was...

Delta power during sleep is modulated by EEG-gated auricular vagal afferent nerve stimulation (EAVANS).

Vagus nerve stimulation (VNS) has many clinical applications under development. In particular, there is a large interest in transcutaneous auricular VNS (taVNS) because it is non-invasive and provides easy access to neuromodulation. The present study proposes a novel approach for electroencephalography (EEG)-gated taVNS, with the ultimate goal of enhancing therapeutic outcomes, including for the treatment of delirium. Delirium arises from an altered state of consciousness and is the most common neuropsychiatric disorder observed in hospitalized patients, especially the elderly. Delirium has been linked to specific disturbances in EEG rhythms. Here, we propose an EEG-gated auricular vagal afferent nerve stimulation (EAVANS) approach to deliver stimulation targeting a specific instantaneous phase of the EEG Delta rhythm to modulate arousal and downstream reduction of neuroinflammation, two of the contributing factors to delirium. We hypothesize that treatment with EAVANS will modulate Delta power, which has been linked with delirium. As dominant Delta power is also a typical feature of non-rapid eye movement (NREM) sleep, we applied a prototype of an EAVANS device on healthy volunteers during sleep to establish preliminary validation. We successfully employed our closed-loop approach to target vagal afference during the rising Delta phase in the range [-π/2 0] radians. We found a significant reduction in Delta wave power for stimulation during the rising Delta phase compared to 1) absence of stimulation, 2) active stimulation during the descending Delta phase, and 3) active stimulation targeting non-vagal territory (i.e. greater auricular nerve) during the rising Delta phase. Further validation of our EEG-gated taVNS approach in the peri-operative period will be needed. As there is presently a lack of effective treatments for delirium, our non-pharmacological and non-invasive approach, if validated, could be easily deployed in clinical settings.Clinical Relevance- Given the serious health consequences and costs associated with delirium, and the absence of effective non-pharmacological treatments, the proposed neuromodulatory approach may be a promising option for reducing delirium and other disorders of consciousness. Our EAVANS prototype system has been tested on healthy volunteers during a NREM sleep state and will require further validation in different patient populations to optimize the proposed technology and gather more evidence to support its clinical utility. This novel non-pharmacological and non-invasive closed-loop neuromodulatory device could be used peri-operatively and in inpatient hospital settings to treat patients at risk of developing delirium. For instance, in a pre-operative setting, this technology may provide an effective preventative "pre-habilitation" approach for patients at high risk of developing delirium. Post-operatively, our technology may help manage patients with delirium more effectively.

Understanding the Neuroplastic Effects of Auricular Vagus Nerve Stimulation in Animal Models of Stroke: A Systematic Review and Meta-Analysis.

Transauricular vagus nerve stimulation (taVNS) is being studied as a feasible intervention for stroke, but the mechanisms by which this non-invasive technique acts in the cortex are still broadly unknown. This study aimed to systematically review the current pre-clinical evidence in the auricular vagus nerve stimulation (aVNS) neuroplastic effects in stroke. We searched, in December of 2022, in Medline, Cochrane, Embase, and Lilacs databases. The authors executed the extraction of the data on Excel. The risk of bias was evaluated by adapted Cochrane Collaboration's tool for animal studies (SYRCLES's RoB tool). A total of 8 studies published between 2015 and 2022 were included in this review, including 391 animal models. In general, aVNS demonstrated a reduction in neurological deficits (SMD = -1.97, 95% CI -2.57 to -1.36, I2 = 44%), in time to perform the adhesive removal test (SMD = -2.26, 95% CI -4.45 to -0.08, I2 = 81%), and infarct size (SMD = -1.51, 95% CI -2.42 to -0.60, I2 = 58%). Regarding the neuroplasticity markers, aVNS showed to increase microcapillary density, CD31 proliferation, and BDNF protein levels and RNA expression. The studies analyzed show a trend of results that demonstrate a significant effect of the auricular vagal nerve stimulation in stroke animal models. Although the aggregated results show high heterogeneity and high risk of bias. More studies are needed to create solid conclusions.

ID: 220554 Effects of VNS on Rectal Tone and Colon Transit in Rats Mediated via Vagal-Sacral Pathway

The parasympathetic modulation of gastrointestinal (GI) functions is accomplished by the activation of either vagal nerve (from esophagus to mid-colon) or sacral nerve (distal colon and anorectum). However, recent studies reported the role of auricular vagal nerve stimulation (aVNS) in controlling motility of the distal colon and rectum, suggesting a crosstalk between vagal and sacral nerves. The aim of this study was testing the hypothesis that exogeneous VNS is capable of altering functions of the distal colon and rectum that are not innervated with the vagus nerve.

The effects of transcutaneous auricular vagal nerve stimulation on cortical GABA-ergic and cholinergic circuits: a transcranial magnetic stimulation study.

Neurophysiological evidence that transcutaneous auricular vagal nerve stimulation (taVNS) affects neuronal signaling at the cortical level is sparse. We used transcranial magnetic stimulation to assess the effect of taVNS on the excitability of intracortical GABA-ergic and cholinergic circuits. In this within-subject, double-blind study on 30 healthy participants, we used TMS paradigms to assess the effect of a single session of taVNS at 100Hz and sham earlobe VNS (sVNS) on short-interval intracortical inhibition (SICI) curve and short-latency afferent inhibition (SAI). Control experiment was performed on additional 15 participants using the same experimental settings, but delivering no stimulation (xVNS). Bayesian statistics were used to assess the differences, producing % values that reflect the certainty that the values of interest were decreased during or after stimulation compared to baseline. taVNS increased SICI (96.3%), whereas sVNS decreased SICI (1.2 %). SAI was not affected by taVNS, while it was decreased during sVNS (1.34% and 9.1 %, for interstimulus intervals 20 and 24ms, respectively). The changes in TMS parameters detected during sVNS were present in the same direction in the control experiment with no stimulation. Our study provides evidence that taVNS increases the activity of cortical GABA-A-ergic system, leaving cortical cholinergic circuits unaffected. Changes in intracortical cortical excitability during sVNS, which were also observed in the control experiment with no stimulation were likely the effect of expectation related to participation in an interventional study.

Transcutaneous auricular vagus nerve stimulation as a potential novel treatment for polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of childbearing age. The etiology of PCOS is multifactorial, and current treatments for PCOS are far from satisfactory. Recently, an imbalanced autonomic nervous system (ANS) with sympathetic hyperactivity and reduced parasympathetic nerve activity (vagal tone) has aroused increasing attention in the pathogenesis of PCOS. In this paper, we review an innovative therapy for the treatment of PCOS and related co-morbidities by targeting parasympathetic modulation based on non-invasive transcutaneous auricular vagal nerve stimulation (ta-VNS). In this work, we present the role of the ANS in the development of PCOS and describe a large number of experimental and clinical reports that support the favorable effects of VNS/ta-VNS in treating a variety of symptoms, including obesity, insulin resistance, type 2 diabetes mellitus, inflammation, microbiome dysregulation, cardiovascular disease, and depression, all of which are also commonly present in PCOS patients. We propose a model focusing on ta-VNS that may treat PCOS by (1) regulating energy metabolism via bidirectional vagal signaling; (2) reversing insulin resistance via its antidiabetic effect; (3) activating anti-inflammatory pathways; (4) restoring homeostasis of the microbiota-gut-brain axis; (5) restoring the sympatho-vagal balance to improve CVD outcomes; (6) and modulating mental disorders. ta-VNS is a safe clinical procedure and it might be a promising new treatment approach for PCOS, or at least a supplementary treatment for current therapeutics.

Effect of transcutaneous auricular vagal nerve stimulation on the fatigue syndrome in patients with gastrointestinal cancers — FATIVA: a randomized, placebo-controlled pilot study protocol

BackgroundCancer-related fatigue (CRF) is defined as a “distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.” CRF is frequently observed in cancer patients even before the initiation of tumor therapy. Its cause is not clear, but in addition to primary effects of therapy, a tumor-induced elevated level of inflammatory cytokines may play a role. Transcutaneous auricular vagal nerve stimulation (taVNS) is a noninvasive way to activate central nervous pathways and modulate pain perception and the immune system. It has positive effects on autoimmune conditions and can also improve fatigue associated with Sjogren’s syndrome. It is the main purpose of this feasibility study to investigate the feasibility of daily taVNS against CRF. Therefore, the stimulation protocol of the newly introduced smartphone app of the manufacturer is evaluated. Additionally, the effect taVNS on CRF and quality of life (QoL) shall be evaluated.MethodsThirty adult patients with gastrointestinal tumors during or after treatment, relevant CRF (Hornheide questionnaire) and life expectancy > 1 year, are enrolled. Patients are randomized to treatment or sham arm and be informed that they will either feel the stimulation or not. Treatment group will receive left-sided tragus above-threshold stimulation with 25 Hz, 250 µs pulse width, and 28-s/32-s on/off paradigm for 4 h throughout the day for 4 weeks. Sham group will receive no stimulation via a nonfunctional electrode. A daily stimulation protocol with time and average intensity is automatically created by a smartphone app connected to the stimulator via Bluetooth®. Multidimensional Fatigue Inventory-20, Short-Form 36 and Beck Depression Inventory questionnaires will be filled out before and after 4 weeks of stimulation.DiscussionPrimarily, the patients’ daily stimulation time and intensity will be evaluated through the electronic protocol after 4 weeks. Secondarily, the effect of taVNS on cancer-related fatigue and QoL will be measured through the questionnaires. As taVNS seems to modulate inflammatory cytokines, this noninvasive method may — if accepted by the patients — be a promising adjunct in the treatment of cancer-related fatigue.Trial registrationThe study was approved by local ethics committee (21–7395) and registered at the DRKS database (DRKS00027481).