taVNS During Multi-site HRV Measurement: Reliability & Agreement Study

Official title

Assessment of Reliability and Agreement of Autonomic Measures Across Different Anatomical Sites During Transcutaneous Auricular Vagus Nerve Stimulation

Overview

This study examines the reliability and agreement of autonomic nervous system measurements obtained from different anatomical sites during transcutaneous auricular vagus nerve stimulation (taVNS). taVNS is a non-invasive electrical stimulation delivered to the ear using a small stimulator. Healthy volunteers aged 18-40 years will participate in one laboratory session. Heart rate and heart rate variability will be recorded from the chest (reference), finger, and arm. Blood pressure and pulse will also be measured. Data will be collected in three standardized periods: T0 (5-minute resting baseline), T1 (10 minutes during taVNS), and T2 (5-minute recovery). The main goal is to determine how closely finger- and arm-based measurements match the chest reference and how consistent these measurements are across the study periods. Participation is voluntary, and participants may withdraw at any time. Expected risks are minimal and may include temporary tingling or mild discomfort at the ear and, rarely, lightheadedness. No direct medical benefit is expected, but the findings may help improve how autonomic responses are monitored during taVNS in future research.

Detailed description

Heart rate variability (HRV) is widely used to quantify autonomic regulation, and non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) may acutely influence cardiac autonomic activity. In both clinical and research settings, autonomic measures can be recorded from different sites using different sensor technologies. However, it is not always clear whether HRV-related indices derived from peripheral recordings (e.g., finger or arm photoplethysmography-based signals) provide comparable results to chest-based reference recordings. This study is designed as a methodological reliability and agreement investigation to determine the consistency of autonomic measures across anatomical sites during a standardized taVNS session.

Participants will attend a single laboratory visit with standardized pre-test instructions (e.g., avoidance of heavy exercise and stimulants before measurement, as applicable). Autonomic measures will be recorded from multiple sites in parallel, using the chest recording as the reference for beat-to-beat intervals. Finger and arm recordings will be obtained simultaneously to allow direct, time-aligned comparisons across sites within the same physiological state. Blood pressure and pulse will be measured during the session to provide complementary hemodynamic context.

The session consists of consecutive measurement periods representing baseline, stimulation, and recovery. Data will be processed using standard HRV pipelines (including artifact inspection and correction when needed) to derive time-domain and frequency-domain indices. The primary analyses will focus on (1) inter-site agreement (bias and limits of agreement) and (2) reliability/consistency metrics across the measurement periods. Agreement will be evaluated using Bland-Altman approaches and related indices, while reliability will be quantified using intraclass correlation coefficients (ICCs) with appropriate model specification. Secondary analyses may explore the association between HRV indices and hemodynamic parameters across periods.

This study involves minimal risk. Expected adverse effects, if any, are transient (e.g., mild ear discomfort or tingling, and rarely lightheadedness). Participant safety will be monitored by the study team throughout the session, and the procedure will be stopped if a participant requests discontinuation or if concerning symptoms occur. Data will be recorded and stored in a de-identified format, and results will be reported at the group level.

Interventions

• Device Transcutaneous auricular vagus nerve stimulation
  Transcutaneous auricular vagus nerve stimulation will be delivered to the cymba conchae region of the auricle using an external stimulator. Stimulation will be set to 25 Hz with a pulse width of 200-300 microseconds. Current intensity will be individually adjusted to a clearly perceptible but non-painful level (typically 0.5-5 mA). Stimulation will be applied for 10 minutes.

Primary outcome measures

• RMSSD inter-site agreement across chest, finger, and arm recordings [Time frame: During a single session: baseline (T0, 5 minutes), stimulation (T1, 10 minutes), and recovery (T2, 5 minutes).]
• SDNN inter-site agreement across chest, finger, and arm recordings [Time frame: During a single session: baseline (T0, 5 minutes), stimulation (T1, 10 minutes), and recovery (T2, 5 minutes).]
• LF power inter-site agreement across chest, finger, and arm recordings [Time frame: During a single session: baseline (T0, 5 minutes), stimulation (T1, 10 minutes), and recovery (T2, 5 minutes).]
• HF power inter-site agreement across chest, finger, and arm recordings [Time frame: During a single session: baseline (T0, 5 minutes), stimulation (T1, 10 minutes), and recovery (T2, 5 minutes).]
• LF/HF ratio inter-site agreement across chest, finger, and arm recordings [Time frame: During a single session: baseline (T0, 5 minutes), stimulation (T1, 10 minutes), and recovery (T2, 5 minutes).]

Secondary outcome measures (3)

• Systolic blood pressure [Time frame: Single session: baseline (5 minutes), stimulation (10 minutes), and recovery (5 minutes)]
• Diastolic blood pressure [Time frame: Single session: baseline (5 minutes), stimulation (10 minutes), and recovery (5 minutes).]
• Heart rate during transcutaneous auricular vagus nerve stimulation [Time frame: Single session: baseline (5 minutes), stimulation (10 minutes), and recovery (5 minutes).]

Eligibility criteria

Inclusion criteria

• Age 18 to 40 years.
• Healthy volunteers without known chronic disease or acute illness at the time of participation.
• Able and willing to comply with study procedures and instructions.
• Provided written informed consent.

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

Turkey (Türkiye) · 1 center

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

Publications

• Coste A, Millour G, Hausswirth C. A Comparative Study Between ECG- and PPG-Based Heart Rate Sensors for Heart Rate Variability Measurements: Influence of Body Position, Duration, Sex, and Age. Sensors (Basel). 2025 Sep 15;25(18):5745. doi: 10.3390/s25185745. PMID 41012985
• 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
• 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
• 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
• 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
• Wang Y, Li SY, Wang D, Wu MZ, He JK, Zhang JL, Zhao B, Hou LW, Wang JY, Wang L, Wang YF, Zhang Y, Zhang ZX, Rong PJ. Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application. Neurosci Bull. 2021 Jun;37(6):853-862. doi: 10.1007/s12264-020-00619-y. Epub 2020 Dec 23. PMID 33355897

Identifiers

NCT: NCT07548723 · taVNS1 · BEU-ETH 2026/01-11

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗