Healthy Volunteers
Conditions
Keywords
Transcutaneous Auricular Vagus Nerve Stimulation, Sham Stimulation, Autonomic Nervous System
Brief summary
This randomized, participant-blinded, sham-controlled interventional study aims to compare the acute effects of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) applied at different durations on autonomic nervous system responses in healthy adults. Participants will be assigned to either an active taVNS group or a sham stimulation group. Within each group, participants will complete three separate study visits in which stimulation will be applied for 5, 10, and 15 minutes in randomized order, with 48- to 72-hour washout intervals between visits. Heart rate variability, heart rate, blood pressure, respiratory rate, and subjective discomfort will be assessed immediately before and after each intervention session. The study is designed to determine whether the acute autonomic effects of taVNS vary according to stimulation duration and whether a duration-related response pattern can be identified.
Detailed description
Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation method in which electrical stimulation is applied to auricular regions innervated by the auricular branch of the vagus nerve. Because of its low-risk profile, non-surgical application, and potential autonomic regulatory effects, taVNS has attracted increasing interest in autonomic physiology and cardiovascular research. Previous studies in healthy individuals suggest that taVNS may influence autonomic balance, particularly through changes in heart rate variability (HRV), heart rate, and related physiological parameters. However, substantial heterogeneity remains across published taVNS studies with regard to stimulation parameters such as frequency, pulse width, current intensity, and intervention duration. Among these parameters, stimulation duration is one of the least standardized, and sham-controlled comparisons of different application durations remain limited. This study is designed to investigate whether the acute autonomic effects of taVNS differ according to stimulation duration. The study uses a randomized, participant-blinded, sham-controlled mixed design. Healthy adults aged 18 to 40 years will be randomized to either an active taVNS group or a sham stimulation group. Participants will remain in their assigned group throughout the study. Within each group, each participant will attend three separate visits and receive stimulation for 5, 10, and 15 minutes in randomized order. Visits will be separated by 48- to 72-hour washout intervals. Active taVNS will be applied bilaterally to the cymba conchae region using non-invasive stimulation parameters consistent with the study protocol. Sham stimulation will be delivered under visually and procedurally similar conditions to minimize expectancy effects. Before and immediately after each intervention session, autonomic and physiological outcomes will be assessed, including heart rate variability derived from RR interval recordings, heart rate, systolic and diastolic blood pressure, respiratory rate, and subjective discomfort measured by a visual analog scale. The primary objective is to compare the acute autonomic responses to active taVNS and sham stimulation across different stimulation durations. The study also aims to explore whether a duration-response relationship exists for autonomic outcomes in healthy adults. Findings from this trial may help inform duration selection in future experimental and clinical taVNS research.
Interventions
DEVICEActive taVNS
Active transcutaneous auricular vagus nerve stimulation will be applied bilaterally to the cymba conchae region. Stimulation frequency will be 25 Hz, pulse width 200 to 300 microseconds, and intensity will be individually adjusted to a clearly perceptible but comfortable level. Depending on the study visit, stimulation will be delivered for 5, 10, or 15 minutes.
DEVICESham stimulation
Sham stimulation will be delivered using the same device under visually similar conditions. The sham procedure will be applied at a non-vagal auricular site or with minimal non-therapeutic stimulation, depending on the study protocol, for 5, 10, or 15 minutes according to the study visit.
Sponsors
Sinop University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Masking description
Participants will be blinded to whether they are assigned to active taVNS or sham stimulation. Investigators and care providers cannot be blinded because of the technical requirements of device setup and application.
Intervention model description
Participants will be randomized to either an active taVNS group or a sham stimulation group and will remain in their assigned group throughout the study. Within each group, participants will complete three separate visits with stimulation durations of 5, 10, and 15 minutes in randomized order, with 48- to 72-hour washout intervals between visits.
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy adults aged 18 to 40 years No known chronic systemic disease Non-smoker No regular medication use, including medications that may affect autonomic or cardiovascular function Able to understand the study procedures and provide written informed consent Willing to comply with study instructions and restrictions related to caffeine, alcohol, and strenuous exercise
Exclusion criteria
Any known chronic systemic disease Current smoker Regular medication use, including medications that may affect autonomic or cardiovascular function Inability to understand the study procedures or provide written informed consent Unwillingness or inability to comply with study instructions and restrictions related to caffeine, alcohol, and strenuous exercise
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in RMSSD | [Time Frame: Baseline (pre-intervention) and immediately after intervention, at each study visit (5, 10, and 15 minutes)] | Change in the root mean square of successive differences (RMSSD), derived from RR interval recordings, from pre-intervention (T0) to post-intervention (T1) after active taVNS or sham stimulation at 5, 10, and 15 minutes. |
| Change in high-frequency heart rate variability (HF-HRV) | [Time Frame: Baseline (pre-intervention) and immediately after intervention, at each study visit (5, 10, and 15 minutes)] | Change in high-frequency heart rate variability (HF-HRV) from pre-intervention (T0) to post-intervention (T1) after active taVNS or sham stimulation at 5, 10, and 15 minutes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in heart rate | [Time Frame: Baseline (pre-intervention) and immediately after intervention, at each study visit (5, 10, and 15 minutes)] | Change in heart rate from pre-intervention to post-intervention after active taVNS or sham stimulation at each study visit. |
| Change in systolic blood pressure | [Time Frame: Baseline (pre-intervention) and immediately after intervention, at each study visit (5, 10, and 15 minutes)] | Change in systolic blood pressure from pre-intervention to post-intervention after active taVNS or sham stimulation at each study visit. |
| Change in diastolic blood pressure | [Time Frame: Baseline (pre-intervention) and immediately after intervention, at each study visit (5, 10, and 15 minutes)] | Change in diastolic blood pressure from pre-intervention to post-intervention after active taVNS or sham stimulation at each study visit. |
| Change in respiratory rate | [Time Frame: Baseline (pre-intervention) and immediately after intervention, at each study visit (5, 10, and 15 minutes)] | Change in respiratory rate from pre-intervention to post-intervention after active taVNS or sham stimulation at each study visit. |
| Change in subjective discomfort assessed by visual analog scale (VAS) | [Time Frame: Baseline (pre-intervention) and immediately after intervention, at each study visit (5, 10, and 15 minutes)] | Change in subjective discomfort assessed by visual analog scale (VAS) from pre-intervention to post-intervention after active taVNS or sham stimulation at each study visit. |
| Change in SDNN | [Time Frame: Baseline (pre-intervention) and immediately after intervention, at each study visit (5, 10, and 15 minutes)] | Change in the standard deviation of normal-to-normal intervals (SDNN) from pre-intervention to post-intervention after active taVNS or sham stimulation at each study visit. |
| Change in LF/HF ratio | [Time Frame: Baseline (pre-intervention) and immediately after intervention, at each study visit (5, 10, and 15 minutes)] | Change in the low-frequency/high-frequency ratio (LF/HF ratio) from pre-intervention to post-intervention after active taVNS or sham stimulation at each study visit. |
Countries
Turkey (Türkiye)
Contacts
CONTACTSefa Haktan Hatık Assistant professor, PhD
Outcome results
None listed