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

NCT ID: NCT07274332

Last Updated: 2025-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-22

Study Completion Date

2026-03-15

Brief Summary

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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

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Participants
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.

Study Groups

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1 - Sham (0 Hz)

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

Dose: 10 minutes

Group Type SHAM_COMPARATOR

Pulsetto FIT™ - Sham tcVNS

Intervention Type 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

2 - 10 Hz tcVNS

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

Group Type EXPERIMENTAL

Pulsetto FIT™ - tcVNS 10 Hz

Intervention Type 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

3 - tcVNS 25 Hz

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

Group Type EXPERIMENTAL

Pulsetto FIT™ - tcVNS 25 Hz

Intervention Type 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

4 - tcVNS 50 Hz

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

Group Type EXPERIMENTAL

Pulsetto FIT™ - tcVNS 50 Hz

Intervention Type 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

5 - tcVNS 100 Hz

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

Group Type EXPERIMENTAL

Pulsetto FIT™ - tcVNS 100 Hz

Intervention Type 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

Interventions

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Pulsetto 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

Intervention Type DEVICE

Pulsetto 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

Intervention Type DEVICE

Pulsetto 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

Intervention Type DEVICE

Pulsetto 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

Intervention Type DEVICE

Pulsetto 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

Intervention Type DEVICE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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SEFA HAKTAN HATIK

OTHER

Sponsor Role lead

Responsible Party

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SEFA HAKTAN HATIK

Assistant Professor

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Sinop University, Türkeli Vocational School (Türkeli MYO)

Türkeli, Sinop, Turkey (Türkiye)

Site Status

Countries

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Turkey (Türkiye)

References

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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.

Reference Type RESULT
PMID: 35134082 (View on PubMed)

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.

Reference Type RESULT
PMID: 33839137 (View on PubMed)

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.

Reference Type RESULT
PMID: 31417453 (View on PubMed)

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

Reference Type RESULT
PMID: 11835542 (View on PubMed)

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.

Reference Type RESULT
PMID: 17081672 (View on PubMed)

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.

Reference Type RESULT
PMID: 26831988 (View on PubMed)

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.

Reference Type RESULT
PMID: 37867315 (View on PubMed)

Other Identifiers

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tcVNS1

Identifier Type: -

Identifier Source: org_study_id

IRB Number (Pending)

Identifier Type: REGISTRY

Identifier Source: secondary_id

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