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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство 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-interventi
• Устройство 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.

Первичные конечные точки

• Change in forced expiratory volume in 1 second (FEV1) [Срок оценки: Single visit: assessed pre-intervention and immediately post-intervention (within the same session).]
• Change in forced vital capacity (FVC) [Срок оценки: Single visit: assessed pre-intervention and immediately post-intervention (within the same session).]
• Change in peak expiratory flow (PEF) [Срок оценки: Single visit: assessed pre-intervention and immediately post-intervention (within the same session).]

Вторичные конечные точки (8)

• Change in RMSSD from chest recordings [Срок оценки: Single visit: assessed pre-intervention and immediately post-intervention (within the same session).]
• Change in SDNN from chest recordings [Срок оценки: Single visit: assessed pre-intervention and immediately post-intervention (within the same session).]
• Change in LF power from chest recordings [Срок оценки: Single visit: assessed pre-intervention and immediately post-intervention (within the same session).]
• Change in HF power from chest recordings [Срок оценки: Single visit: assessed pre-intervention and immediately post-intervention (within the same session).]
• Change in LF/HF ratio from chest recordings [Срок оценки: Single visit: assessed pre-intervention and immediately post-intervention (within the same session).]
• Change in systolic blood pressure (SBP) [Срок оценки: Single visit: assessed pre-intervention and immediately post-intervention (within the same session).]
• Change in diastolic blood pressure (DBP) [Срок оценки: Single visit: assessed pre-intervention and immediately post-intervention (within the same session).]
• Change in heart rate [Срок оценки: Single visit: assessed pre-intervention and immediately post-intervention (within the same session).]

Критерии участия

Критерии включения

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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Другое

Центры проведения

Turkey (Türkiye) · 1 центр

• Güzelyurt Neighborhood, Mustafa Bozkurt Street, No: 9, 57900, Türkeli, Sinop, Türkiye — Sinop

Публикации

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• Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986 Feb 8;1(8476):307-10. PMID 2868172
• 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. PMID 18839484
• 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. PMID 27330520
• 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. PMID 8598068
• 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. PMID 36543841
• 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. PMID 34937487
• 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. PMID 38729100

Идентификаторы

NCT: NCT07482930 · taVNS2 · BEU-IRB 2026/02-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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