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NCT Number: NCT07274332

Frequency-Dependent Effects of Auricular Vagus Nerve Stimulation on Autonomic and Cardiovascular Parameters

This randomized, sham-controlled, crossover study investigates the acute autonomic effects of transcutaneous cervical vagus nerve stimulation (tcVNS) applied at five different frequencies (0 Hz/sham, 10 Hz, 25 Hz, 50 Hz, 100 Hz) in healthy adults. The primary objective is to determine how stimulation frequency modulates heart rate variability (HRV), blood pressure, and respiratory rate. The study aims to establish a frequency-specific dose-response model using validated physiological measurements.

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Key information

Conditions

Vagus Nerve Stimulation Autonomic Nervous System Blood Pressure Healthy Volunteers Heart Rate Pathologic Processes Pathological Conditions, Signs and Symptoms Respiration Respiration Disorders Respiratory Aspiration Respiratory Tract Diseases

Age range

18 year–30 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Sinop University, Türkeli Vocational School (Türkeli MYO)

Türkeli, Sinop, 57900, Turkey (Türkiye)

About this study

Transcutaneous cervical vagus nerve stimulation (tcVNS) is a non-invasive neuromodulation technique capable of activating afferent vagal pathways projecting to autonomic brainstem nuclei. Although previous studies demonstrate tcVNS-related modulation of autonomic functions, the frequency-response relationship remains insufficiently explored.

This crossover trial randomizes participants to receive five stimulation conditions (sham, 10 Hz, 25 Hz, 50 Hz, 100 Hz) in counterbalanced order. HRV (Polar H10), blood pressure (Omron), and respiratory rate (Kinovea-based thoracoabdominal video tracking) are collected pre- and post-stimulation. Washout between sessions is ≥48 hours.

The study provides one of the first systematic evaluations of frequency-dependent tcVNS effects in healthy adults.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 18-30 years
  • Healthy (self-reported)
  • No cardiovascular, neurological, metabolic or psychiatric disorders
  • No regular medication affecting autonomic function
  • Non-smoker
  • BMI 18-29.9

Exclusion criteria

  • Pregnancy
  • Cardiac arrhythmia
  • Hypertension or hypotension
  • Chronic respiratory disorders
  • Active infection
  • Metal implants in cervical area
  • Epilepsy
  • Syncope history
  • Prior vagus stimulation experience

Treatment and study plan

Pulsetto FIT™ - Sham tcVNS

Device

The Pulsetto FIT™ device is placed bilaterally on the cervical region (posterior margin of the sternocleidomastoid muscle).

In the sham condition, the device displays normal operational lights but delivers no electrical stimulation (0 Hz; inactive mode).

This condition is used for blinding and as the control comparator. Dose: 10 minutes

Pulsetto FIT™ - tcVNS 10 Hz

Device

Bilateral transcutaneous cervical vagus nerve stimulation delivered via the Pulsetto FIT™ device at 10 Hz, 250 µs pulse width.

Current intensity adjusted to a mild, non-painful tingling sensation, individualized for each participant.

Dose: 10 minutes

Pulsetto FIT™ - tcVNS 25 Hz

Device

Bilateral tcVNS using the Pulsetto FIT™ device at 25 Hz, 250 µs pulse width. Stimulation intensity set at a comfortable sensory level. Dose: 10 minutes

Pulsetto FIT™ - tcVNS 50 Hz

Device

Bilateral cervical vagus nerve stimulation via Pulsetto FIT™ at 50 Hz, 250 µs pulse width.

Intensity adjusted to a tolerable sensory level without discomfort. Dose: 10 minutes

Pulsetto FIT™ - tcVNS 100 Hz

Device

Bilateral tcVNS delivered with the Pulsetto FIT™ device at 100 Hz, 250 µs pulse width.

Highest stimulation frequency used in this protocol; current intensity individualized per participant comfort.

Dose: 10 minutes

Primary outcomes

  1. Heart Rate Variability (HRV) Changes (ΔRMSSD, ΔHF, ΔLF/HF)

    Time frame: Pre- vs Post-stimulation (5-min segments)(5-minute baseline, 5-minute stimulation, 5-minute post period)

    HRV is recorded using a validated high-resolution heart rate monitor (Polar H10) during a 5-minute resting baseline (T0) and a 5-minute post-stimulation period (T2).

    The following time- and frequency-domain parameters are analyzed: RMSSD, HF (ms²), and LF/HF ratio.

    Artefact correction is performed using standard HRV processing methods. Acute autonomic response is quantified by calculating change scores (Δ = post-pre) for each stimulation frequency.

Secondary outcomes

  1. Blood Pressure (SBP, DBP, MAP)

    Time frame: Pre- vs Post-stimulation (5-minute baseline, 5-minute stimulation, 5-minute post period)

    Two readings are taken at each time point from the right arm with a validated automatic sphygmomanometer, and the average systolic, diastolic, and mean arterial pressure values are used for analysis.

    Changes are calculated as post-pre (Δ values) to assess the acute physiological effect of each stimulation frequency..

  2. Respiratory Rate (breaths per minute)

    Time frame: Pre- vs Post-stimulation (5-minute video segments) (5-minute baseline, 5-minute stimulation, 5-minute post period)

    Respiratory rate is assessed by video-based thoracoabdominal motion tracking at baseline (T0) and after stimulation (T2).

    Videos are analyzed using Kinovea motion-tracking software, and a 1-minute stable segment is used to determine breaths per minute by counting inspiratory peaks.

    Respiratory changes are expressed as Δ values (post-pre) to account for individual differences and improve HRV interpretability.Respiratory rate is assessed by video-based thoracoabdominal motion tracking at baseline (T0) and after stimulation (T2).

    Videos are analyzed using Kinovea motion-tracking software, and a 1-minute stable segment is used to determine breaths per minute by counting inspiratory peaks.

    Respiratory changes are expressed as Δ values (post-pre) to account for individual differences and improve HRV interpretability.

  3. Discomfort Level (Visual Analog Scale, 0-10)

    Time frame: Pre- vs Post-stimulation (5-minute baseline, 5-minute stimulation, 5-minute post period)

    Participants report their perceived discomfort level at baseline (T0) and immediately after stimulation (T2) using a 0-10 Visual Analog Scale (VAS).

    The scale captures any sensory discomfort associated with tcVNS. Changes are calculated by subtracting the pre-stimulation score from the post-stimulation score (ΔVAS).

Sponsors and collaborators

Lead sponsor

SEFA HAKTAN HATIK

Other

Registry information

Official study title

Acute Effects of Different Frequencies of Auricular Vagus Nerve Stimulation on HRV, Blood Pressure, and Respiratory Rate: A Sham-Controlled, Randomized, Crossover Dose-Response Study

Acronym: AVNS-DRC

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Dec 10, 2025
Registry last updated
Dec 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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