Effect of Vagus Stimulation on Peripheral Glucose Metabolism

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

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).

Study Overview

• Status: Completed
• Conditions: Insulin Resistance; Glucose Intolerance
• Intervention / Treatment: Device: Transauricular vagus nerve stimulation; Device: Transauricular sham stimulation

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Tübingen, Germany, 72076
    • University of Tuebingen, Department of Internal Medicine IV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Principal Investigator: Martin Heni, MD, University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2018
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 20, 2018

Study Registration Dates

• First Submitted: July 30, 2018
• First Submitted That Met QC Criteria: July 30, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): January 10, 2019
• Last Update Submitted That Met QC Criteria: January 9, 2019
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Hyperglycemia; Glucose Intolerance; Insulin Resistance
• Other Study ID Numbers: 608/2017BO1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Due to ethical restrains, we will not be able to share patient level data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No