Effect of Vagus Stimulation on Peripheral Glucose Metabolism

Study Overview
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Brief Summary
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Two important mechanisms play a major role in the pathogenesis of type 2 diabetes: insulin resistance of the target tissues and the impaired insulin secretion from pancreatic β-cells. Postprandial factors (such as insulin) are perceived by the human brain and induce signals that regulate glucose metabolism via the parasympathetic nervous system. Transcutaneous auricular vagus nerve stimulation (tVNS) can be used on the outer ear to stimulate the auricular branch of the vagus nerve in humans. Heart rate variability (HRV) in healthy people can be significantly increased via tVNS, indicating a shift from sympathetic activity to parasympathetic activity. The hypothesis is that this postprandial shift results in a change in peripheral glucose metabolism. In turn, the increased parasympathetic activity could potentially result in a change in postprandial insulin sensitivity or secretion. To test this hypothesis, this study investigates the effect of vagal stimulation versus sham stimulation on insulin sensitivity, on insulin secretion, glucose tolerance, resting energy expenditure, and on parasympathetic tone (analysis of heart rate variability).

Official Title
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Effekte Der Transkutanen Aurikularen Vagus-Nervenstimulation (tVNS) Auf Die Postprandiale Stoffwechselregulation im Menschen

Conditions
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Insulin Resistance, Glucose Intolerance

Intervention / Treatment
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* Device: Transauricular vagus nerve stimulation
* Device: Transauricular sham stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HbA1c <6.5% Must be able to understand the explanations of the study and the instructions Exclusion Criteria: Any relevant (according to investigator's judgment) cardiovascular disease Neurological and psychiatric disorders Diabetes mellitus Active implants (e.g. pacemaker, cochlear implant, cerebral shunt) asthma skin diseases on the ear

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Transauricular vagus nerve stimulation<br>Non invasive vagus nerve stimulation will be conducted with Cerbomed NEMOS via the left ear. | Device: Transauricular vagus nerve stimulation<br>* Stimulation will be performed for 150 minutes (throughout the entire OGTT).<br>|
| Sham Comparator: Transauricular sham stimulation<br>Non invasive sham stimulation will be conducted with Cerbomed NEMOS via the left ear lobe. | Device: Transauricular sham stimulation<br>* Sham stimulation will be performed for 150 minutes (throughout the entire OGTT)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole body insulin sensitivity | Insulin sensitivity will be assessed by a 75g OGTT. | 0-120 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin secretion | Insulin secretion will be assessed by a 75g OGTT | 0-120 min | 
| Glucose tolerance | Glucose tolerance will be assessed by a 75g OGTT | 0-120 min | 
| Resting energy expenditure | Resting energy expenditure will be assessed by indirect calorimetry | 140-160 min. after start of stimulation | 
| Heart rate variability | Heart rate variability will be assessed from continuous ecg recordings | -30 - 120 min |