Balance, Autonomic Response, and Sensory Modulation to Dosage of Mechanical Vagal Stimulation in Healthy Adults

NCT06541808 | Completed

• 1 other identifier: EK Nr: 1349/2024
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

The vagus nerve (VN) plays a crucial role in regulating vital functions (heart rate, blood pressure, digestion, and immune response) and maintaining communication between internal organs and the brain. Recent studies have highlighted the therapeutic potential of VN stimulation (VNS) in treating various conditions such as drug-resistant epilepsy, postural control deficit, COVID-19 infection, chronic pain, and intestinal disorders. In addition, there is growing evidence that the molecules released by the VN neurons affect the function of the gut microbiota and that the molecules released by the bacteria in our gut affect the activity of the VN neurons. In particular, Dr. Giacomo Carta (the leader of this study) has shown how painless neck movements, i.e. mechanical VNS (mVNS), can be applied without adverse effects, representing a potential alternative to invasive methods commonly used today. To further investigate the impact of this novel mVNS, this study aims to evaluate the changes induced by three mVNS protocols on physiological parameters such as resting heart rate, and Heart Rate Variability (HRV) at rest, balance in standing, the perceived intensity of mechanical stimuli using the established clinical method of QST (quantitative sensory testing), fecal transit speed, and the molecular composition of stool (for this, stool samples are analyzed). In particular, stool analysis is very relevant for understanding normal digestion. The present research aims to define the optimal intensity of mVNS and to investigate the therapeutic potential of VNS in the treatment of autonomic dysfunction (such as too low or too high heart rate, too low or too fast digestion, throbbing headaches), as well as falls prevention and pain.

Conditions

Vagus Nerve Autonomic Disorder; Heart Rate; Pain; Equilibrium; Disorder, Labyrinth; Microbial Colonization

Keywords

Non-invasive Vagus Nerve stimulation; Heart Rate; Equilibrium; Pain modulation; Gut microbiota

Outcome Measures

Primary Outcomes (3)

• Heart Rate at rest

  Heart rate is recorded continuously from 2 minutes before to 2 minutes after the stimulation using a fingertip infrared pulse oximeter. Heart rate will be measured in beats per minute.

  The outcome will be measured before the stimulation protocol and immediately after the stimulation protocol

• Heart Rate Variability at rest

  Polar H10 (1000 Hz) Chest Strap (rubber band placed comfortably around the chest above the xiphoid process level) for data acquisition will be worn by the participant for the duration of the assessment and the stimulation protocol. ECG waves will be acquired via Bluetooth to Elite HRV (Version 5.5.9, Asheville, NC, USA) on an Android device. HRV results from Elite HRV displayed on the app will be recorded for analysis with an Open HRV reading 2 minutes before the stimulation and 2 minutes immediately after. At the end of the data acquisition session, the chest strap will be removed. Distance between R peaks in the ECG, defined as RR Interval (Interbeat intervals \[IBIs\]) will be used as a reference to define HRV.

  The outcome will be measured before the stimulation protocol and immediately after the stimulation protocol

• Mechanical Pain Intensity

  These tests will be adopted to assess peripheral and central sensitization phenomena. Tests will be administered once for each site, using Neuropen with a Neurotip (disposable needle with a defined pressure of 40 g) and by applying 75 g pressure monofilament for 2 seconds on the skin site. If the stimulus is perceived as a pinprick by the participant, it will be requested to rate the pain intensity (NRS, "0 = no pain" to "10 = worst imaginable pain").

  The outcome will be measured before the stimulation protocol and immediately after the stimulation protocol

Secondary Outcomes (6)

• Wind-up ratio

  The outcome will be measured before the stimulation protocol and immediately after the stimulation protocol

• One-leg support test

  The outcome will be measured before the stimulation protocol and immediately after the stimulation protocol

• Mechanical pressure intensity

  The outcome will be measured before the stimulation protocol and immediately after the stimulation protocol

• The Gastrointestinal Symptom Rating Scale

  The outcome will be measured before the stimulation protocol, immediately after the stimulation protocol, and one week after the stimulation

• The Bristol Stool Form Scale

  The outcome will be measured for 1 week before and for 2 weeks after the administration of e week after the stimulation

Study Arms (4)

mechanical Vagus Nerve Stimulation (Low Intensity)

EXPERIMENTAL

4 minutes of mechanical vagal stimulation (2 minutes on each side) administered only once along the entire experiment

Other: mechanical Vagus Nerve Stimulation (Low Intensity)

mechanical Vagus Nerve Stimulation (Intermediate Intensity)

EXPERIMENTAL

12 minutes of mechanical vagal stimulation(3 sessions of 2 minutes of stimulation, with 2 minutes of rest for each side) administered only once along the entire experiment

Other: mechanical Vagus Nerve Stimulation (Intermediate Intensity)

mechanical Vagus Nerve Stimulation (High Intensity)

EXPERIMENTAL

16 minutes of mechanical vagal stimulation (8 minutes on each side) administered only once along the entire experiment

Other: mechanical Vagus Nerve Stimulation (High Intensity)

Sham Vagus Nerve Stimulation

SHAM COMPARATOR

Participants will be treated with a fake vagus stimulation not able to stretch the vagus nerve

Other: Sham mechanical Vagus Nerve Stimulation

Interventions

mechanical Vagus Nerve Stimulation (Low Intensity) OTHER

The stimulation consists of a combination of normal neck movements, performed in a comfortable supine position, which can selectively stimulate the VN. In particular. The participant will be stimulated supine on a comfortable massage/treatment bed with the experimenter standing at the cranial short side of the bed. All the neck movements will be gently performed with a combination of upper cervical flexion and contralateral lateral flexion to load the intracranial portion of the vagus nerve. The ipsilateral neck rotation will be combined to load the cervical tract of the nerve. Keeping the participant's head in the final movements combination the upper abdomen will be gently moved caudally to load the thoracic tract and intermittent gentle impulses 1 each second will be administered. The stimulation will be provided for 2 consecutive minutes for each side, only once for the experiment duration.

mechanical Vagus Nerve Stimulation (Low Intensity)

mechanical Vagus Nerve Stimulation (Intermediate Intensity) OTHER

The stimulation consists of a combination of normal neck movements, performed in a comfortable supine position, which can selectively stimulate the VN. In particular. The participant will be stimulated supine on a comfortable massage/treatment bed with the experimenter standing at the cranial short side of the bed. All the neck movements will be gently performed with a combination of upper cervical flexion and contralateral lateral flexion to load the intracranial portion of the vagus nerve. The ipsilateral neck rotation will be combined to load the cervical tract of the nerve. Keeping the participant's head in the final movements combination the upper abdomen will be gently moved caudally to load the thoracic tract and intermittent gentle impulses 1 each second will be administered. The stimulation will be provided for 3 sessions of 2 minutes, with 2 minutes of rest for each side. stimulation will be provided only once for the experiment duration.

mechanical Vagus Nerve Stimulation (Intermediate Intensity)

mechanical Vagus Nerve Stimulation (High Intensity) OTHER

The stimulation consists of a combination of normal neck movements, performed in a comfortable supine position, which can selectively stimulate the VN. In particular. The participant will be stimulated supine on a comfortable massage/treatment bed with the experimenter standing at the cranial short side of the bed. All the neck movements will be gently performed with a combination of upper cervical flexion and contralateral lateral flexion to load the intracranial portion of the vagus nerve. The ipsilateral neck rotation will be combined to load the cervical tract of the nerve. Keeping the participant's head in the final movements combination the upper abdomen will be gently moved caudally to load the thoracic tract and intermittent gentle impulses 1 each second will be administered. The stimulation will be provided for 8 consecutive minutes for each side, only once for the experiment duration.

mechanical Vagus Nerve Stimulation (High Intensity)

Sham mechanical Vagus Nerve Stimulation OTHER

Participants will be treated with a fake vagus stimulation by letting the operator hold the neck of the participant in one hand and placing the other hand on the abdomen without any stretch on the vagus nerve

Sham Vagus Nerve Stimulation

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• agreement to participate by signing the informed consent form, being 18-60 years old, and sober

You may not qualify if:

• participants having significant neck pain, headache, or leg pain \[with Numeric Pain Rating Scale (NPRS) greater than 3/10\],
• pregnancy
• recent neck or cardiovascular surgery or significant trauma in the preceding 3 months
• diagnosis of cancer or inflammatory disorders (fever),
• spinal cord or cauda equina signs,
• widespread neurological disorders affecting the tone of the limbs and neck muscles
• underlying diseases, such as diabetes mellitus.
• pace-maker
• antibiotic prescription during the last 3 months
• gastrointestinal surgery,
• lower extremity injury (acute or overuse) that prevented them from participating in sports activities for at least one day in the previous 6 months.

Sponsors & Collaborators

• University of Vienna: lead

Study Sites (1)

UVienna

Vienna, State of Vienna, 1090, Austria

Location

MeSH Terms

Conditions

Pain; Communicable Diseases

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infections; Disease Attributes; Pathologic Processes

Study Officials

• Giacomo Carta, PhD

  University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Postdoc PhD Researcher

Study Record Dates

• First Submitted: July 3, 2024
• First Posted: August 7, 2024
• Study Start: December 2, 2024
• Primary Completion: April 22, 2026
• Study Completion: April 22, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Immediately following the publication. No end date.
• Access Criteria: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Locations

AU (1)