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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство 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
• Устройство 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
• Устройство 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
• Устройство 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
• Устройство 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

Первичные конечные точки

• Heart Rate Variability (HRV) Changes (ΔRMSSD, ΔHF, ΔLF/HF) [Срок оценки: Pre- vs Post-stimulation (5-min segments)(5-minute baseline, 5-minute stimulation, 5-minute post period)]

Вторичные конечные точки (3)

• Blood Pressure (SBP, DBP, MAP) [Срок оценки: Pre- vs Post-stimulation (5-minute baseline, 5-minute stimulation, 5-minute post period)]
• Respiratory Rate (breaths per minute) [Срок оценки: 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) [Срок оценки: Pre- vs Post-stimulation (5-minute baseline, 5-minute stimulation, 5-minute post period)]

Критерии участия

Критерии включения

• 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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Простое слепое

Основная цель

Фундаментальное исследование

Центры проведения

Turkey (Türkiye) · 1 центр

• Sinop University, Türkeli Vocational School (Türkeli MYO) — Türkeli

Публикации

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• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT07274332 · tcVNS1 · IRB Number (Pending)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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