Autonomic Nervous System, Blood Pressure, Healthy Volunteers, Heart Rate, Respiration, Vagus Nerve Stimulation
Conditions
Keywords
Transcutaneous Cervical Vagus Nerve Stimulation, Neuromodulation, Non-invasive Vagus Stimulation, Parasympathetic Activation, Heart Rate Variability
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.
Interventions
DEVICEPulsetto FIT™ - Sham tcVNS
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
DEVICEPulsetto FIT™ - tcVNS 10 Hz
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
DEVICEPulsetto FIT™ - tcVNS 25 Hz
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
DEVICEPulsetto FIT™ - tcVNS 50 Hz
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
DEVICEPulsetto FIT™ - tcVNS 100 Hz
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
Sponsors
SEFA HAKTAN HATIK
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
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.
Intervention model description
All participants receive each of the five stimulation conditions in randomized counterbalanced order (Williams Latin Square). Each visit includes a 10-minute tcVNS session and before/after physiological recordings. Washout between visits is ≥48 hours.
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
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 * Epilepsy * Syncope history * Prior vagus stimulation experience
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Heart Rate Variability (HRV) Changes (ΔRMSSD, ΔHF, ΔLF/HF) | 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
| Measure | Time frame | Description |
|---|---|---|
| Blood Pressure (SBP, DBP, MAP) | 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.. |
| Respiratory Rate (breaths per minute) | 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. |
| Discomfort Level (Visual Analog Scale, 0-10) | 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). |
Countries
Turkey (Türkiye)
Outcome results
None listed