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This randomized, participant-blinded, sham-controlled crossover study aims to investigate the acute effects of different frequency applications of transcutaneous auricular vagus nerve stimulation (taVNS) on autonomic physiological responses in healthy adults. Participants will receive sham (0 Hz), 10 Hz, 25 Hz, 50 Hz, and 100 Hz taVNS in separate sessions with washout periods between visits. Heart rate variability, blood pressure, pulse rate, respiratory rate, and subjective discomfort will be assessed before and after each intervention session.
The vagus nerve is a major regulator of the parasympathetic branch of the autonomic nervous system. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique applied to auricular regions innervated by the auricular branch of the vagus nerve. Although taVNS has been reported to modulate autonomic function, the acute physiological effects of different stimulation frequencies remain insufficiently characterized.
This study is designed as a randomized, participant-blinded, sham-controlled crossover trial in healthy adults aged 18 to 40 years. Each participant will undergo five intervention conditions in randomized order: sham (0 Hz), 10 Hz, 25 Hz, 50 Hz, and 100 Hz taVNS. Sessions will be separated by 48 to 72 hours to minimize carryover effects. Each stimulation session will last 10 minutes.
Primary autonomic outcomes will be derived from heart rate variability parameters obtained using a Polar H10 chest strap and analyzed with Kubios HRV software. Secondary physiological outcomes will include systolic and diastolic blood pressure, pulse rate, respiratory rate, and subjective discomfort measured using a visual analog scale. The study aims to identify frequency-specific autonomic response profiles and to evaluate whether respiratory rate influences heart rate variability changes associated with taVNS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sham taVNS | Sham Comparator | Participants receive sham stimulation during one study session. |
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| taVNS 10 Hz | Experimental | Participants receive active transcutaneous auricular vagus nerve stimulation at 10 Hz during one study session. |
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| taVNS 25 Hz | Experimental | Participants receive active transcutaneous auricular vagus nerve stimulation at 25 Hz during one study session. |
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| taVNS 50 Hz | Experimental | Participants receive active transcutaneous auricular vagus nerve stimulation at 50 Hz during one study session. |
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| taVNS 100 Hz | Experimental | Participants receive active transcutaneous auricular vagus nerve stimulation at 100 Hz during one study session. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sham taVNS | Device | Sham stimulation is delivered under conditions similar to active taVNS without meaningful vagal stimulation. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in Root Mean Square of Successive Differences (RMSSD) | Change in the root mean square of successive differences (RMSSD) from pre-intervention to post-intervention under each stimulation condition. | Immediately before and immediately after each 10-minute intervention session |
| Change in High-Frequency Heart Rate Variability (HF-HRV) | Change in high-frequency heart rate variability (HF-HRV) from pre-intervention to post-intervention under each stimulation condition. | Immediately before and immediately after each 10-minute intervention session |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Standard Deviation of Normal-to-Normal RR Intervals (SDNN) | Change in the standard deviation of normal-to-normal RR intervals (SDNN) from pre-intervention to post-intervention under each stimulation condition. | Immediately before and immediately after each 10-minute intervention session |
| Change in Low-Frequency (LF) Power |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sefa Haktan Hatık, MSc, PhD | Contact | 90 368 271 55 28 | haktanhtk@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Artvin Coruh University, Artvin Vocational School, Disabled Care and Rehabilitation Laboratory | Artvin | Turkey (Türkiye) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29034226 | Background | Shaffer F, Ginsberg JP. An Overview of Heart Rate Variability Metrics and Norms. Front Public Health. 2017 Sep 28;5:258. doi: 10.3389/fpubh.2017.00258. eCollection 2017. | |
| 27898202 | Background | Yakunina N, Kim SS, Nam EC. Optimization of Transcutaneous Vagus Nerve Stimulation Using Functional MRI. Neuromodulation. 2017 Apr;20(3):290-300. doi: 10.1111/ner.12541. Epub 2016 Nov 29. |
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Each participant will receive all five intervention conditions (sham, 10 Hz, 25 Hz, 50 Hz, and 100 Hz taVNS) in randomized order across separate visits, with a 48- to 72-hour washout period between sessions.
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Participants will be blinded to whether the intervention session involves active taVNS or sham stimulation. The care provider/investigator cannot be blinded because of the technical requirements of device application and condition setup.
| taVNS 10 Hz | Device | Active transcutaneous auricular vagus nerve stimulation applied for 10 minutes at 10 Hz. |
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| taVNS 25 Hz | Device | Active transcutaneous auricular vagus nerve stimulation applied for 10 minutes at 25 Hz. |
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| taVNS 50 Hz | Device | Active transcutaneous auricular vagus nerve stimulation applied for 10 minutes at 50 Hz. |
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| taVNS 100 Hz | Device | Active transcutaneous auricular vagus nerve stimulation applied for 10 minutes at 100 Hz. |
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Change in low-frequency (LF) power of heart rate variability from pre-intervention to post-intervention under each stimulation condition. |
| Immediately before and immediately after each 10-minute intervention session |
| Change in LF/HF Ratio | Change in the ratio of low-frequency to high-frequency heart rate variability (LF/HF ratio) from pre-intervention to post-intervention under each stimulation condition. | Immediately before and immediately after each 10-minute intervention session |
| Change in Systolic Blood Pressure | Change in systolic blood pressure from pre-intervention to post-intervention under each stimulation condition. | Immediately before and immediately after each 10-minute intervention session |
| Change in Diastolic Blood Pressure | Change in diastolic blood pressure from pre-intervention to post-intervention under each stimulation condition. | Immediately before and immediately after each 10-minute intervention session |
| Change in Pulse Rate | Change in pulse rate from pre-intervention to post-intervention under each stimulation condition. | Immediately before and immediately after each 10-minute intervention session |
| Change in Respiratory Rate | Change in respiratory rate from pre-intervention to post-intervention under each stimulation condition. | Immediately before and immediately after each 10-minute intervention session |
| Change in Subjective Discomfort Assessed by Visual Analog Scale (VAS) | Subjective discomfort will be assessed using a Visual Analog Scale (VAS) ranging from 0 to 10, where 0 indicates no discomfort and 10 indicates the worst possible discomfort. Higher scores indicate greater discomfort. Change in VAS score from pre-intervention to post-intervention will be evaluated under each stimulation condition. | Immediately before and immediately after each 10-minute intervention session |
| 11835542 | Background | Peuker ET, Filler TJ. The nerve supply of the human auricle. Clin Anat. 2002 Jan;15(1):35-7. doi: 10.1002/ca.1089. |
| 25573069 | Background | Frangos E, Ellrich J, Komisaruk BR. Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans. Brain Stimul. 2015 May-Jun;8(3):624-36. doi: 10.1016/j.brs.2014.11.018. Epub 2014 Dec 6. |