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

NCT07274332 | Not Yet Recruiting DMC

• 2 other identifiers: tcVNS1IRB Number (Pending)
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Vagus Nerve Stimulation; Heart Rate; Autonomic Nervous System; Blood Pressure; Respiration; Healthy Volunteers

Keywords

Transcutaneous Cervical Vagus Nerve Stimulation; Neuromodulation; Non-invasive Vagus Stimulation; Parasympathetic Activation; Heart Rate Variability

Outcome Measures

Primary Outcomes (1)

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

  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.

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

Secondary Outcomes (3)

• 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)

Study Arms (5)

1 - Sham (0 Hz)

SHAM COMPARATOR

Intervention Type: Pulsetto FIT™ tcVNS Device Intervention Name: Sham tcVNS Description: Device placed on bilateral cervical region; no electrical current delivered. Dose: 10 minutes

Device: Pulsetto FIT™ - Sham tcVNS

2 - 10 Hz tcVNS

EXPERIMENTAL

Intervention Type:Pulsetto FIT™ tcVNS Device Intervention Name: tcVNS (10 Hz) Description: Bilateral cervical stimulation at 10 Hz, 250 μs pulse width. Duration: 10 minutes

Device: Pulsetto FIT™ - tcVNS 10 Hz

3 - tcVNS 25 Hz

EXPERIMENTAL

Intervention Type:Pulsetto FIT™ tcVNS Device Intervention Name: tcVNS (25 Hz) Description: Bilateral cervical stimulation at 25 Hz, 250 μs pulse width. Duration: 10 minutes

Device: Pulsetto FIT™ - tcVNS 25 Hz

4 - tcVNS 50 Hz

EXPERIMENTAL

Intervention Type:Pulsetto FIT™ tcVNS Device Intervention Name: tcVNS (50 Hz) Description: Bilateral cervical stimulation at 50 Hz, 250 μs pulse width. Duration: 10 minutes

Device: Pulsetto FIT™ - tcVNS 50 Hz

5 - tcVNS 100 Hz

EXPERIMENTAL

Intervention Type:Pulsetto FIT™ tcVNS Device Intervention Name: tcVNS (100 Hz) Description: Bilateral cervical stimulation at 100 Hz, 250 μs pulse width. Duration: 10 minutes

Device: Pulsetto FIT™ - tcVNS 100 Hz

Interventions

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

1 - Sham (0 Hz)

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

2 - 10 Hz tcVNS

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

3 - tcVNS 25 Hz

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

4 - tcVNS 50 Hz

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

5 - tcVNS 100 Hz

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• SEFA HAKTAN HATIK: lead

Study Sites (1)

Sinop University, Türkeli Vocational School (Türkeli MYO)

Türkeli, Sinop, 57900, Turkey (Türkiye)

Location

Related Publications (7)

• Kranz S, Lukacs J, Bishop J, Block ME. Intergeneration transfer of diet patterns? Parental self-report of diet and their report of their young adult children with ASD. PLoS One. 2022 Feb 8;17(2):e0263445. doi: 10.1371/journal.pone.0263445. eCollection 2022.

  PMID: 35134082 RESULT

• Alsoufi B. Curb Your Enthusiasm for the Ozaki Procedure in Small Children. Ann Thorac Surg. 2022 Jan;113(1):378-379. doi: 10.1016/j.athoracsur.2021.03.085. Epub 2021 Apr 8. No abstract available.

  PMID: 33839137 RESULT

• Nordahl HM, Wells A. Metacognitive Therapy of Early Traumatized Patients With Borderline Personality Disorder: A Phase-II Baseline Controlled Trial. Front Psychol. 2019 Jul 30;10:1694. doi: 10.3389/fpsyg.2019.01694. eCollection 2019.

  PMID: 31417453 RESULT

• Peuker ET, Filler TJ. The nerve supply of the human auricle. Clin Anat. 2002 Jan;15(1):35-7. doi: 10.1002/ca.1089.

  PMID: 11835542 RESULT

• Grossman P, Taylor EW. Toward understanding respiratory sinus arrhythmia: relations to cardiac vagal tone, evolution and biobehavioral functions. Biol Psychol. 2007 Feb;74(2):263-85. doi: 10.1016/j.biopsycho.2005.11.014. Epub 2006 Nov 1.

  PMID: 17081672 RESULT

• Zhang Y, Xiao S, Feng H, Zhang L, Zhou Z, Hu W. Self-interference cancellation using dual-drive Mach-Zehnder modulator for in-band full-duplex radio-over-fiber system. Opt Express. 2015 Dec 28;23(26):33205-13. doi: 10.1364/OE.23.033205.

  PMID: 26831988 RESULT

• Fernandes TL, Viezzer Fernandes B, Jitumori C, Franco GCN. A Case Report of Oral Bisphosphonate Treatment for Osteoporosis Leading to Atypical Femoral Fracture and Pathologic Mandibular Fracture. Am J Case Rep. 2023 Oct 23;24:e941144. doi: 10.12659/AJCR.941144.

  PMID: 37867315 RESULT

MeSH Terms

Conditions

Respiratory Aspiration

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: November 27, 2025
• First Posted: December 10, 2025
• Study Start: December 22, 2025
• Primary Completion: January 31, 2026
• Study Completion: March 15, 2026
• Last Updated: December 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)