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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Heart Rate Variability (HRV) Changes (ΔRMSSD, ΔHF, ΔLF/HF)
Study Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Single (Participant)
Masking Description
Participants are blinded to the stimulation condition. The Pulsetto FIT™ device displays active lights and interface indicators in both sham and active frequencies, but delivers no current in the sham arm (0 Hz).
The investigator administering the stimulation is aware of the condition due to device programming requirements.
Eligibility Criteria
- Ages
- 18 Years to 30 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
- •Syncope history
- •Prior vagus stimulation experience
Outcomes
Primary Outcomes
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
- Blood Pressure (SBP, DBP, MAP)(Pre- vs Post-stimulation (5-minute baseline, 5-minute stimulation, 5-minute post period))
- Respiratory Rate (breaths per minute)(Pre- vs Post-stimulation (5-minute video segments) (5-minute baseline, 5-minute stimulation, 5-minute post period))
- Discomfort Level (Visual Analog Scale, 0-10)(Pre- vs Post-stimulation (5-minute baseline, 5-minute stimulation, 5-minute post period))
Investigators
SEFA HAKTAN HATIK
Assistant Professor
Sinop University