Response of the Autonomic Nervous System to Auricular Stimulation of the Vagus Nerve (x)

Vasoconstriction Disorder of Extremities Clinical Trial

— AURIX  

Official title:

Response of the Autonomic Nervous System to Auricular Stimulation of the Vagus Nerve (x)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04130893
• Other study ID #: 18-36 AURIX
• Status: Terminated
• Phase: N/A
• Start date: January 17, 2019
• Est. completion date: November 21, 2019

Study information

• Verified date: January 2022
• Source: Hôpital Européen Marseille
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

While invasive vagal stimulation has proven its therapeutic effectiveness over the past 20 years, particularly in the treatment of epilepsy or depression, its implementation is hampered by the high cost, high technicality and sometimes significant side effects. Non-invasive vagal stimulation, most often electric, is a less expensive therapeutic alternative and easier to implement, although the level of evidence is lower than that of invasive stimulation.

Some so-called traditional therapies, such as acupuncture, also stimulate certain parts of the ear by mechanical means, most often by puncturing the ear or the concha. In these traditional therapies, more than one hundred stimulation points have been described, each precisely positioned according to an empirical topography.

However, electrical non-invasive stimulation recognizes only three areas of interest on the ear, which are the areas of sensitive innervation, namely the afferences of the vagus nerve in the concha, which is the only one used in practice, the large occipital nerve on the lobe and part of the helix, and the auriculotemporal nerve on the rest of the auricular flag.

In this study, we would like to explore the justification for the topographic precision, adopted by traditional therapies, for non-invasive vagal stimulation on the concha.

Description:

Main objective: to measure the physiological impact of two auricular stimuli on the same innervation territory but with opposite actions according to traditional therapies.

An identical physiological response on both stimulation points would be an argument against the topographical precision adopted by traditional therapies; conversely, a different physiological response would suggest the existence of a somatotopy nestled in the same innervation territory.

Secondary objectives:

• Determine, by sinus variability analysis, the intensity of the sympathetic and parasympathetic cardiac response of mechanical stimulation of the ear concha.

• Determine the existence of a blockage of the sympathetic reaction on cutaneous vasoconstriction after mechanical stimulation of the ear concha.

• Measure the relationship between sinus variability and paradoxical skin vasodilation after exposure to cold, as considered in the protocol.

To explore the justification for the topographical precision adopted by traditional therapies, we designed an experiment that consists of studying the autonomous, sympathetic and parasympathetic response to two stimuli performed over two different times.

The sympathetic stimulation will be done by immersing the right hand up to the wrist in a tub of cold water maintained at 5°C Mechanical parasympathetic stimulation will be performed on the ear in two different locations, by placing an adapted needle through an introducer to respect a standardized insertion depth.

The autonomous response will be measured by sinus variability, which responds to a double innervation, sympathetic and parasympathetic, and by the capillary skin response, which responds only to a sympathetic innervation.

The capillary skin response is measured by the amplitude and latency of the paradoxical vasodilation reflex following thermal stimulation, in this case the immersion of a limb's tip in cold water.

The study will consist of 3 sessions, as shown in the figure below. This is a prospective crossover study.

During the first session, the inclusion and non-inclusion criteria will be checked, then a water immersion test will be carried out to ensure the good tolerance of this test and then determine the basic values.

In the absence of acclimatization, the paradoxical vasodilation reflex is highly reproducible. During the second and third sessions, a mechanical stimulation will be done to the ear during the skin immersion test.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: November 21, 2019
• Est. primary completion date: November 21, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Healthy volunteers, male and female, aged 18 to 60 years

• BMI (Body mass index) <=30

• Not participating in another clinical study with an investigational product

Exclusion Criteria:

• Drug treatment for cardiological, neurological or anticoagulant purposes

• History of diabetes, known neuropathy, high blood pressure, heart rhythm disorders, syncope or palpitation

• Known cryoglobulinemia

• Subject with Raynaud's syndrome

• Intra-auricular device of the piercing type,

• Psychoactive substance use, excessive alcohol consumption (>2 units per day chronically or >6 units per day recreationally) and tobacco (>5 cigarettes per day)

• Subject unable to read French

• Subject covered by Articles L1121-5 to 1121-8 of the Public Health Code, namely:

• Pregnant, postpartum and breastfeeding women

• Persons deprived of their liberty by a judicial or administrative decision

• Persons undergoing psychiatric care under Articles L3112-1 and L3113-1 who are not covered by the provisions of Article L1121-8

• Minors

• Persons of full age who are subject to a legal protection measure or who are unable to express their consent

Related Conditions & MeSH terms

• Vasoconstriction Disorder of Extremities

Intervention

Behavioral:
• stimulation of G13 then G15
Study participant randomized into arm A will undergo a stimulation of point G13 at session N°2, then stimulation of point G15 at session N°3.
• stimulation of G15 then G13
Study participant randomized into arm B will undergo a stimulation of point G15 at session N°2, then stimulation of point G13 at session N°3.

Locations

Country	Name	City	State
France	Hôpital Européen Marseille	Marseille	Paca

Sponsors (2)

Lead Sponsor	Collaborator
Hôpital Européen Marseille	Aix Marseille Université

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sinus variability	measured by cardiofrequency meter(ACTIWAVE ®)	20 minutes
Primary	Skin temperature changes	measured by thermocouples placed on the following fingers: thumb, middle finger and ear of the right hand. The values and times of the minimum and maximum temperatures (latency and amplitude of (CIVD) Cold-Induced VasoDilatation waves) are measured	20 minutes
Secondary	Pain reported by the participant	Measured by visual analogue scale; this scale ranges from 0 to 10; 0 being no pain, 10 being excruciating pain.	20 minutes