Pilot Study - Auricular Vagus Nerve Stimulation Effects on Cardiovascular Parameters

Study Overview
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Brief Summary
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The purpose of this pilot study is to evaluate the effect of auricular autonomous nervous system stimulation on cardiovascular parameters and sympathovagal balance in healthy subjects. It is investigated if auricular vagal nerve stimulation affects heart rate variability as well as peripheral local blood perfusion, and if this effect depends on the site of stimulation in the auricle, whereas four distinct stimulation points are tested.

Official Title
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Functional Mapping of Auricular Vagal Stimulation Points on Cardiovascular Parameters in Healthy Subjects - Pilot Study

Conditions
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Modulation of Cardiovascular Parameters and Sympathovagal Balance in Healthy Subjects

Intervention / Treatment
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* Device: PrimeStim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: men and women aged 20 to 50 years Exclusion Criteria: participation in a clinical trial in the last 5 weeks diseases which may affect the autonomous nervous system (e.g., diabetes mellitus) confounding medical treatment with known effects on the autonomous nervous system (e.g., beta blocker) drug abuse active implanted devices pregnancy or nursing

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: auricular vagus nerve stimulation<br>Study participants (healthy) are treated with auricular vagus nerve stimulation using five needle electrodes connected to an electrical stimulation device (PrimeStim). After acclimatization the stimulation is turned on for 20 minutes followed by 20 minutes of paused stimulation, 20 minutes of stimulation, and 10 minutes paused stimulation. This intervention is repeated on four consecutive days, whereas at each intervention only one of the four stimulation points (and one fixed reference point) is stimulated. Needle electrodes are applied at each study visit. Stimulation points in the auricle are stimulated in random order. One stimulation pattern is tested. Stimulation amplitudes are adjusted with respect to a distinct but comfortable sensation at the auricle. During the described protocol various biosignals are continuously recorded, including ECG, respiration, blood perfusion, oxygen saturation, transcutaneous oxygen tension, blood pressure and skin temperature. | Device: PrimeStim<br>* Intermittent auricular vagus nerve stimulation at different ear points<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in heart rate variability (HRV) related to stimulation site in the auricle | Heart rate variability will be assessed as, e.g., standard deviation in heart rate over a time window of 5 minutes (2.5 minutes overlap), total power or low to high frequency power. Changes in assessed heart rate variability parameters will be assessed and compared between subjects with respect to stimulation site using statistical tests. | within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles | 
| change in local blood perfusion index (BPI) related to stimulation site in the auricle | Blood perfusion index at the foot will be assessed as peak-peak amplitude (systolic to diastolic) divided by the mean signal value of optically measured blood perfusion. Changes in mean value and standard deviation of local blood perfusion index will be assessed and compared between subjects with respect to stimulation site using statistical tests. | within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of local BPI in upper and lower extremities | Local BPI is assessed using optical sensors on the foot and the finger of participants. Changes in mean value of BPI are analyzed using statistical tests. | within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles | 
| Changes in blood pressure | Blood pressure is continuously measured using inflatable finger cuffs. | within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles | 
| Changes in respiratory activity | Respiratory activity is monitored using a respiratory belt. | within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles | 
| Changes in oxygen saturation of the toe |  | within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles | 
| Changes in partial transcutaneous oxygen pressure of the forefoot |  | within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles | 
| Changes in foot skin temperature |  | within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles | 
| Changes of C reactive protein- and leukocyte-concentration in serum |  | at screening and at the last day of intervention | 
| Tolerance of stimulation | Tolerance of stimulation is assessed by free survey. | at each day of intervention at the stimulation cycles | 
| Perception of Stimulation | Perception of stimulation is assessed by free survey. | at each day of intervention at the stiumulation cycles | 
| Adverse effects of stimulation |  | within 4 days of intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vagus nerve stimulation effects on heart rate variability and peripheral blood perfusion