Transcutaneous Auricular Vagus Nerve Stimulation and Spirometry: Sham-Controlled Randomized Trial (taVNS-SPIRO)

Acute Effects Transcutaneous Auricular Vagus Nerve Stimulation on Spirometric Parameters in Healthy Individuals: A Sham-Controlled Randomized Study

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.

Study Overview

• Status: Recruiting
• Conditions: Spirometry; Respiratory Function Tests; Vagus Nerve Stimulations; Blood Pressure Monitoring; Autonomic Nervous System (ANS) Functioning and Mood State
• Intervention / Treatment: Device: Transcutaneous auricular vagus nerve stimulation; Device: Sham transcutaneous auricular stimulation

Detailed Description

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation approach delivered through the external ear. The auricular branch of the vagus nerve provides an accessible peripheral route that may influence autonomic regulation and, through autonomic-respiratory interactions, potentially affect respiratory function. Although taVNS has been investigated across several physiological domains, evidence regarding its acute effects on spirometric outcomes in healthy individuals remains limited. This study is designed to evaluate whether a single, brief session of bilateral taVNS produces measurable short-term changes in standard spirometric parameters compared with a sham procedure.

This is a sham-controlled, randomized, single-blind, parallel-group trial conducted in healthy volunteers. Participants are allocated to either active bilateral taVNS or sham stimulation using a predefined randomization procedure and concealed assignment. To minimize expectancy effects, participants are blinded to group allocation, and active and sham procedures use the same device appearance and session structure. Active stimulation is delivered via electrodes positioned on auricular regions targeted for vagal innervation, whereas sham stimulation uses an alternative placement intended to minimize vagal activation while maintaining a similar sensory experience. Stimulation parameters are standardized across participants, with intensity individually titrated to a clearly perceptible but non-painful level.

The primary outcomes are acute pre-to-post changes in spirometric measures obtained using standardized spirometry procedures. Key spirometric endpoints include forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF). Secondary physiological measures may include heart rate, heart rate variability indices, and blood pressure to characterize autonomic and hemodynamic responses and to support safety monitoring during the session. All measurements are collected within the same visit, with spirometry performed immediately before and after the stimulation procedure following consistent instructions and quality criteria.

Data analysis will focus on between-group comparisons of change scores (post minus pre) for spirometric outcomes. Depending on distributional assumptions, analyses will use appropriate parametric or non-parametric methods; when relevant, models adjusting for baseline values will be applied (e.g., ANCOVA with baseline spirometry as a covariate). Effect sizes and confidence intervals will be reported to support interpretability. Safety will be monitored throughout the visit; stimulation will be discontinued if a participant experiences significant discomfort or requests stopping.

The study involves minimal risk. Expected adverse effects are transient and mild (e.g., localized tingling or mild discomfort at the ear). Rarely, lightheadedness may occur; participants will be monitored and the procedure stopped if necessary. Data will be stored in a coded/de-identified format and reported at the group level.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: SEFA HAKTAN HATIK, MSc, PhD; Phone Number: 4601 +90 368 271 55 28; Email: haktanhtk@gmail.com

Study Locations

• Turkey (Türkiye)
  • Sinop, Turkey (Türkiye), 57900
    • Recruiting
    • Güzelyurt Neighborhood, Mustafa Bozkurt Street, No: 9, 57900, Türkeli, Sinop, Türkiye
    • Sub-Investigator: Uğur BAĞCI, PT, MSc
    • Sub-Investigator: Mesut ARSLAN, MSc, PhD
    • Sub-Investigator: Berkay Eren PEHLİVANOĞLU, MSc, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged 18-40 years.
• Healthy volunteers.
• Able to perform spirometry and follow study instructions.
• Provided written informed consent.

Exclusion Criteria:

• Any cardiovascular disease, cardiac arrhythmia, hypertension, or related condition.
• Any neurological disorder (e.g., diabetes mellitus, peripheral neuropathy, epilepsy).
• Any diagnosed psychiatric disorder.
• Any respiratory disease (e.g., asthma, chronic obstructive pulmonary disease).
• Pregnancy or suspected pregnancy.
• Ear conditions that prevent stimulation (infection, open wound, pain/tenderness) or presence of a piercing at/near the stimulation site.
• Vigorous exercise within 24 hours prior to measurement.
• Caffeine intake, smoking, or alcohol consumption within 4-6 hours prior to measurement.
• Marked intolerance or hypersensitivity to the device or the procedure.
• Inability to follow instructions during measurements or refusal to complete the session.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active bilateral auricular vagus nerve stimulation; Participants receive active bilateral transcutaneous auricular vagus nerve stimulation using an external stimulator. Electrodes are placed on auricular regions targeted for vagal innervation (bilaterally). Stimulation is applied for approximately 10 minutes with standardized parameters and individually adjusted intensity to a clearly perceptible but non-painful level. Spirometry (e.g., FVC, FEV1, PEF) is performed before and after the session; heart rate, heart rate variability, and blood pressure may also be recorded.	Device: Transcutaneous auricular vagus nerve stimulation; Transcutaneous auricular vagus nerve stimulation is delivered bilaterally using an external stimulator with electrodes placed on auricular regions targeted for vagal innervation (e.g., cymba conchae). Stimulation is applied for approximately 10 minutes. Parameters are standardized (e.g., 25 Hz; pulse width 200-300 microseconds), and current intensity is individually adjusted to a clearly perceptible but non-painful level. The procedure is performed in a single visit with pre- and post-intervention spirometry and physiological monitoring as specified in the protocol.
Sham Comparator: Sham auricular stimulation (control); Participants receive sham stimulation using the same device appearance and session structure. Electrodes are placed on an ear location intended to minimize vagal activation (e.g., ear lobule), and stimulation is delivered at a minimal/low level to mimic sensation without therapeutic stimulation. The same pre- and post-session spirometry and physiological measurements are collected as in the active arm.	Device: Sham transcutaneous auricular stimulation; Sham stimulation uses the same device, setup, and session duration to mimic the active procedure. Electrodes are placed on an ear location intended to minimize vagal activation (e.g., ear lobule), and stimulation is delivered at a minimal/low level to provide a similar sensation without therapeutic vagal stimulation. Pre- and post-session spirometry and other measurements are collected identically to the active arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in forced expiratory volume in 1 second (FEV1)	Forced expiratory volume in 1 second (FEV1), reported in liters (L), will be measured immediately before and immediately after the intervention. The outcome will be defined as the pre-to-post change (post minus pre), and between-group differences in change between active stimulation and sham control will be evaluated.[FVC], and peak expiratory flow [PEF]) will be measured immediately before and immediately after the intervention. The primary endpoint is the pre-to-post change (post minus pre) and the between-group difference in change between active stimulation and sham control.	Single visit: assessed pre-intervention and immediately post-intervention (within the same session).
Change in forced vital capacity (FVC)	Forced vital capacity (FVC), reported in liters (L), will be measured immediately before and immediately after the intervention. The outcome will be defined as the pre-to-post change (post minus pre), and between-group differences in change between active stimulation and sham control will be evaluated.	Single visit: assessed pre-intervention and immediately post-intervention (within the same session).
Change in peak expiratory flow (PEF)	Peak expiratory flow (PEF), reported in liters per minute (L/min), will be measured immediately before and immediately after the intervention. The outcome will be defined as the pre-to-post change (post minus pre), and between-group differences in change between active stimulation and sham control will be evaluated.	Single visit: assessed pre-intervention and immediately post-intervention (within the same session).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in RMSSD from chest recordings	Heart rate variability will be recorded from chest-based beat-to-beat intervals before and after the intervention in a standardized resting condition. The root mean square of successive differences (RMSSD), reported in milliseconds (ms), will be derived from these recordings. The endpoint is the pre-to-post change (post minus pre) and the between-group difference in change between active bilateral stimulation and sham control.	Single visit: assessed pre-intervention and immediately post-intervention (within the same session).
Change in SDNN from chest recordings	Heart rate variability will be recorded from chest-based beat-to-beat intervals before and after the intervention in a standardized resting condition. The standard deviation of normal-to-normal intervals (SDNN), reported in milliseconds (ms), will be derived from these recordings. The endpoint is the pre-to-post change (post minus pre) and the between-group difference in change between active bilateral stimulation and sham control.	Single visit: assessed pre-intervention and immediately post-intervention (within the same session).
Change in LF power from chest recordings	Heart rate variability will be recorded from chest-based beat-to-beat intervals before and after the intervention in a standardized resting condition. Low-frequency (LF) power, reported in milliseconds squared (ms²), will be derived from these recordings. The endpoint is the pre-to-post change (post minus pre) and the between-group difference in change between active bilateral stimulation and sham control.	Single visit: assessed pre-intervention and immediately post-intervention (within the same session).
Change in HF power from chest recordings	Heart rate variability will be recorded from chest-based beat-to-beat intervals before and after the intervention in a standardized resting condition. High-frequency (HF) power, reported in milliseconds squared (ms²), will be derived from these recordings. The endpoint is the pre-to-post change (post minus pre) and the between-group difference in change between active bilateral stimulation and sham control.	Single visit: assessed pre-intervention and immediately post-intervention (within the same session).
Change in LF/HF ratio from chest recordings	Heart rate variability will be recorded from chest-based beat-to-beat intervals before and after the intervention in a standardized resting condition. The low-frequency/high-frequency (LF/HF) ratio, reported as a unitless measure, will be derived from these recordings. The endpoint is the pre-to-post change (post minus pre) and the between-group difference in change between active bilateral stimulation and sham control.	Single visit: assessed pre-intervention and immediately post-intervention (within the same session).
Change in systolic blood pressure (SBP)	Systolic blood pressure (SBP), reported in millimeters of mercury (mmHg), will be measured before and after the intervention under standardized conditions. The endpoint is the pre-to-post change (post minus pre) and the between-group difference in change between active stimulation and sham control.	Single visit: assessed pre-intervention and immediately post-intervention (within the same session).
Change in diastolic blood pressure (DBP)	Diastolic blood pressure (DBP), reported in millimeters of mercury (mmHg), will be measured before and after the intervention under standardized conditions. The endpoint is the pre-to-post change (post minus pre) and the between-group difference in change between active stimulation and sham control.	Single visit: assessed pre-intervention and immediately post-intervention (within the same session).
Change in heart rate	Heart rate, reported in beats per minute (bpm), will be measured before and after the intervention under standardized conditions. The endpoint is the pre-to-post change (post minus pre) and the between-group difference in change between active stimulation and sham control.	Single visit: assessed pre-intervention and immediately post-intervention (within the same session).

Collaborators and Investigators

• Sponsor: SEFA HAKTAN HATIK
• Collaborators: Sinop University

Publications and helpful links

General Publications

• Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996 Mar 1;93(5):1043-65. No abstract available.
• Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986 Feb 8;1(8476):307-10.
• Shrout PE, Fleiss JL. Intraclass correlations: uses in assessing rater reliability. Psychol Bull. 1979 Mar;86(2):420-8. doi: 10.1037//0033-2909.86.2.420.
• Kim AY, Marduy A, de Melo PS, Gianlorenco AC, Kim CK, Choi H, Song JJ, Fregni F. Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Sci Rep. 2022 Dec 21;12(1):22055. doi: 10.1038/s41598-022-25864-1.
• Wang L, Wang Y, Wang Y, Wang F, Zhang J, Li S, Wu M, Li L, Rong P. Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. Expert Rev Med Devices. 2022 Jan;19(1):43-61. doi: 10.1080/17434440.2022.2020095. Epub 2022 Jan 13.
• Zou N, Zhou Q, Zhang Y, Xin C, Wang Y, Claire-Marie R, Rong P, Gao G, Li S. Transcutaneous auricular vagus nerve stimulation as a novel therapy connecting the central and peripheral systems: a review. Int J Surg. 2024 Aug 1;110(8):4993-5006. doi: 10.1097/JS9.0000000000001592.
• Koo TK, Li MY. A Guideline of Selecting and Reporting Intraclass Correlation Coefficients for Reliability Research. J Chiropr Med. 2016 Jun;15(2):155-63. doi: 10.1016/j.jcm.2016.02.012. Epub 2016 Mar 31.
• Paleczny B, Seredynski R, Ponikowska B. Inspiratory- and expiratory-gated transcutaneous vagus nerve stimulation have different effects on heart rate in healthy subjects: preliminary results. Clin Auton Res. 2021 Apr;31(2):205-214. doi: 10.1007/s10286-019-00604-0. Epub 2019 Apr 2.

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2026
• Primary Completion (Estimated): April 20, 2026
• Study Completion (Estimated): April 25, 2026

Study Registration Dates

• First Submitted: February 22, 2026
• First Submitted That Met QC Criteria: March 16, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: spirometry; blood pressure; autonomic nervous system; transcutaneous auricular vagus nerve stimulation; pulmonary function test; sham stimulation
• Other Study ID Numbers: taVNS2; BEU-IRB 2026/02-1 (Other Identifier: Bitlis Eren University Non-Interventional Clinical Research Ethics Committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be publicly shared at this time. Study results will be reported in the manuscript in aggregated form. De-identified IPD may be made available upon reasonable request by contacting the corresponding author, subject to appropriate ethical and institutional approvals and data-use conditions.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No