Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Obesity and Insulin Resistance

NCT04926415 | Completed FDA Device

• 1 other identifier: 0079_2021
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Being overweight or obese has been associated with insulin resistance contributing to an increased risk for the development of type II diabetes. Food intake, metabolic rate, and blood glucose levels are regulated by the autonomic nervous system, including the vagus nerve. This study evaluates the hypothesis that non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) affects hormones that regulate food intake and blood glucose levels in a way that is consistent with reduced food intake and lower blood glucose levels. The investigators further hypothesize that these effects of taVNS depend on body weight. In a cross-over design generally healthy study participants will receive either taVNS or a sham intervention for 30 minutes on two separate study days. The order of the intervention on the two study days will be randomized and the two study days are at least one week apart. Based on body mass index (BMI) study participants are assigned to either a normal weight (BMI\<25), overweight (BMI\<30), or obese (BMI\>30) group. Capillary blood samples taken by finger prick before and after the intervention on each study day will be analyzed for blood glucose concentration and hormones that are linked to food intake and blood glucose levels. In addition, autonomic function will be assessed by heart rate variability analysis of ECG recordings obtained before, during, and after the intervention on each study day.

Conditions

Diabetes Mellitus, Type 2; Obesity

Keywords

insulin resistance; blood glucose; insulin; glucagon; C-peptide; GLP-1; GIP; ghrelin; leptin; PAI-1; resistin; vistatin; adipsin; adiponectin; vagus nerve stimulation; transcutaneous auricular vagus nerve stimulation

Outcome Measures

Primary Outcomes (26)

• Change in Blood Glucose Concentration induced by taVNS

  The blood glucose concentration is measured before and after application of taVNS from capillary blood samples obtained by finger prick. The change in blood glucose concentration is determined as the difference in the two blood glucose concentrations (after taVNS minus before taVNS).

  During the taVNS intervention (30 min).

• Change in Blood Glucose Concentration induced by sham taVNS

  The blood glucose concentration is measured before and after application of sham taVNS from capillary blood samples obtained by finger prick. The change in blood glucose concentration is determined as the difference in the two blood glucose concentrations (after sham taVNS minus before sham taVNS).

  During the sham taVNS intervention (30 min).

• Change in Insulin Plasma Concentration induced by taVNS

  Using capillary blood samples obtained by finger prick the insulin plasma concentration will be determined using a Bioplex assay. The insulin plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).

  During the taVNS intervention (30 min).

• Change in Insulin Plasma Concentration induced by sham taVNS

  Using capillary blood samples obtained by finger prick the insulin plasma concentration will be determined using a Bioplex assay. The insulin plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).

  During the taVNS intervention (30 min).

• Change in Glucagon Plasma Concentration induced by taVNS

  Using capillary blood samples obtained by finger prick the glucagon plasma concentration will be determined using a Bioplex assay. The glucagon plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).

  During the taVNS intervention (30 min).

• Change in Glucagon Plasma Concentration induced by sham taVNS

  Using capillary blood samples obtained by finger prick the glucagon plasma concentration will be determined using a Bioplex assay. The glucagon plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).

  During the taVNS intervention (30 min).

• Change in C-Peptide Plasma Concentration induced by taVNS

  Using capillary blood samples obtained by finger prick the C-peptide plasma concentration will be determined using a Bioplex assay. The C-peptide plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).

  During the taVNS intervention (30 min).

• Change in C-Peptide Plasma Concentration induced by sham taVNS

  Using capillary blood samples obtained by finger prick the C-peptide plasma concentration will be determined using a Bioplex assay. The C-peptide plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).

  During the taVNS intervention (30 min).

• Change in GLP-1 Plasma Concentration induced by taVNS

  Using capillary blood samples obtained by finger prick the GLP-1 plasma concentration will be determined using a Bioplex assay. The GLP-1 plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).

  During the taVNS intervention (30 min).

• Change in GLP-1 Plasma Concentration induced by sham taVNS

  Using capillary blood samples obtained by finger prick the GLP-1 plasma concentration will be determined using a Bioplex assay. The GLP-1 plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).

  During the taVNS intervention (30 min).

• Change in GIP Plasma Concentration induced by taVNS

  Using capillary blood samples obtained by finger prick the GIP plasma concentration will be determined using a Bioplex assay. The GIP plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).

  During the taVNS intervention (30 min).

• Change in GIP Plasma Concentration induced by sham taVNS

  Using capillary blood samples obtained by finger prick the GIP plasma concentration will be determined using a Bioplex assay. The GIP plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).

  During the taVNS intervention (30 min).

• Change in Ghrelin Plasma Concentration induced by taVNS

  Using capillary blood samples obtained by finger prick the ghrelin plasma concentration will be determined using a Bioplex assay. The ghrelin plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).

  During the taVNS intervention (30 min).

• Change in Ghrelin Plasma Concentration induced by sham taVNS

  Using capillary blood samples obtained by finger prick the ghrelin plasma concentration will be determined using a Bioplex assay. The ghrelin plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).

  During the taVNS intervention (30 min).

• Change in Leptin Plasma Concentration induced by taVNS

  Using capillary blood samples obtained by finger prick the leptin plasma concentration will be determined using a Bioplex assay. The leptin plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).

  During the taVNS intervention (30 min).

• Change in Leptin Plasma Concentration induced by sham taVNS

  Using capillary blood samples obtained by finger prick the leptin plasma concentration will be determined using a Bioplex assay. The leptin plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).

  During the taVNS intervention (30 min).

• Change in PAI-1 Plasma Concentration induced by taVNS

  Using capillary blood samples obtained by finger prick the PAI-1 plasma concentration will be determined using a Bioplex assay. The PAI-1 plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).

  During the taVNS intervention (30 min).

• Change in PAI-1 Plasma Concentration induced by sham taVNS

  Using capillary blood samples obtained by finger prick the PAI-1 plasma concentration will be determined using a Bioplex assay. The PAI-1 plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).

  During the taVNS intervention (30 min).

• Change in Resistin Plasma Concentration induced by taVNS

  Using capillary blood samples obtained by finger prick the resistin plasma concentration will be determined using a Bioplex assay. The resistin plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).

  During the taVNS intervention (30 min).

• Change in Resistin Plasma Concentration induced by sham taVNS

  Using capillary blood samples obtained by finger prick the resistin plasma concentration will be determined using a Bioplex assay. The resistin plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).

  During the taVNS intervention (30 min).

• Change in Vistatin Plasma Concentration induced by taVNS

  Using capillary blood samples obtained by finger prick the vistatin plasma concentration will be determined using a Bioplex assay. The vistatin plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).

  During the taVNS intervention (30 min).

• Change in Vistatin Plasma Concentration induced by sham taVNS

  Using capillary blood samples obtained by finger prick the vistatin plasma concentration will be determined using a Bioplex assay. The vistatin plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).

  During the taVNS intervention (30 min).

• Change in Adipsin Plasma Concentration induced by taVNS

  Using capillary blood samples obtained by finger prick the adipsin plasma concentration will be determined using a Bioplex assay. The adipsin plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).

  During the taVNS intervention (30 min).

• Change in Adipsin Plasma Concentration induced by sham taVNS

  Using capillary blood samples obtained by finger prick the adipsin plasma concentration will be determined using a Bioplex assay. The adipsin plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).

  During the taVNS intervention (30 min).

• Change in Adiponectin Plasma Concentration induced by taVNS

  Using capillary blood samples obtained by finger prick the adipsin plasma concentration will be determined using a Bioplex assay. The adiponectin plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).

  During the taVNS intervention (30 min).

• Change in Adiponectin Plasma Concentration induced by sham taVNS

  Using capillary blood samples obtained by finger prick the adipsin plasma concentration will be determined using a Bioplex assay. The adiponectin plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).

  During the taVNS intervention (30 min).

Secondary Outcomes (2)

• Changes in Autonomic Function induced by taVNS

  During the taVNS intervention (30 min).

• Changes in Autonomic Function induced by sham taVNS

  During the sham taVNS intervention (30 min).

Study Arms (3)

Normal Weight

EXPERIMENTAL

This arm consists of study participants with a body mass index (BMI) of less than 25. These study participants will participate on two study days. On one study day non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) and on the other study day a sham procedure will be performed. Capillary blood samples (finger prick) will be obtained before and after the interventions on both study days. The ECG will be recorded before, during, and after the intervention on both study days.

Device: taVNS; Device: Sham taVNS

Overweight

EXPERIMENTAL

This arm consists of study participants with a body mass index (BMI) of more than 25 but less than 30. These study participants will participate on two study days. On one study day non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) and on the other study day a sham procedure will be performed. Capillary blood samples (finger prick) will be obtained before and after the interventions on both study days. The ECG will be recorded before, during, and after the intervention on both study days.

Device: taVNS; Device: Sham taVNS

Obese

EXPERIMENTAL

This arm consists of study participants with a body mass index (BMI) of more than 30. These study participants will participate on two study days. On one study day non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) and on the other study day a sham procedure will be performed. Capillary blood samples (finger prick) will be obtained before and after the interventions on both study days. The ECG will be recorded before, during, and after the intervention on both study days.

Device: taVNS; Device: Sham taVNS

Interventions

taVNS DEVICE

A bipolar clip electrode is attached to the auricle at the location of the cymba conchae. Electrical stimulation (30 Hz stimulation frequency, 300 μs pulse width) is applied for 30 min. The stimulation current is determined individually for each participant by slowly increasing the stimulation current until the participants feel a mild tingling sensation at the site of the electrode. Then the current is gradually reduced until the tingling sensation disappears. This current will then be used for taVNS. A TENS 7000 or EMS 7500 device (510(k): K080661) is used.

Also known as: Transcutaneous Auricular Vagus Nerve Stimulation

Normal Weight; Obese; Overweight

Sham taVNS DEVICE

A bipolar clip electrode is attached to the auricle at the location of the cymba conchae but no electrical current is applied to the electrode.

Also known as: Sham Transcutaneous Auricular Vagus Nerve Stimulation

Normal Weight; Obese; Overweight

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Generally healthy

You may not qualify if:

• Age under 18 years
• Pregnancy
• Acute illnesses/fever
• Any medication that interferes with the autonomic nervous system (e.g., beta blockers)
• Any medication that interferes with glucose metabolism (e.g., antidiabetic drugs)
• Any medication that interferes with lipid metabolism (e.g., statins)
• Any medical conditions that interfere with the autonomic nervous system
• Type 1 or Type 2 diabetes
• Epilepsy
• Cardiac conditions, including arrhythmia
• Vestibulocochlear neuronitis or nerve damage (e.g., hearing loss or tinnitus)
• Skin irritation/inflammation at the stimulation site at the ear
• Current drug or alcohol abuse

Sponsors & Collaborators

• Burrell College of Osteopathic Medicine: lead

Study Sites (1)

Burrell College of Osteopathic Medicine

Las Cruces, New Mexico, 88001, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity; Insulin Resistance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism

Study Officials

• Harald M Stauss, MD, PhD

  Burrell College of Osteopathic Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The participants will not be told if transcutaneous auricular vagus nerve stimulation (taVNS) or the sham procedure will be performed. However, it is possible that participants will find out that the stimulation is being performed by a mild tingling sensation associated with taVNS.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pharmacology

Model Details: Research participants in three groups (normal weight, overweight, obese) will undergo 2 study days (at least one week apart) during which either transcutaneous auricular vagus nerve stimulation (taVNS) or a sham procedure will be performed. The order of the intervention (taVNS or sham procedure) on the two study days is randomized.

Study Record Dates

• First Submitted: June 2, 2021
• First Posted: June 15, 2021
• Study Start: June 14, 2021
• Primary Completion: April 26, 2022
• Study Completion: April 26, 2022
• Last Updated: April 28, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)