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

NCT ID: NCT04926415

Last Updated: 2022-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-14
• Study Completion Date: 2022-04-26

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.

Detailed Description

Clinical studies and experimental studies in animals have demonstrated that cervical vagus nerve stimulation causes weight loss in obese patients and has profound effects on glucose homeostasis. Furthermore, anorexic and antidiabetic effects have been reported in response to non-invasive transcutaneous auricular vagus nerve stimulation (taVNS). Thus, non-invasive taVNS may potentially prevent insulin resistance in obesity. The objective of this study is to investigate the acute effects of taVNS on hormones and adipokines linking obesity with insulin resistance in human subjects. The hypothesis of this study is that acute application of taVNS elicits anti-diabetic effects through modulation of plasma levels of insulin, glucagon, C-peptide, GLP-1 (stimulates insulin and suppresses glucagon release), and GIP (gastric inhibitory polypeptide, stimulates insulin secretion). Furthermore, the investigators hypothesize that taVNS elicits anorexic effects by modulating ghrelin and leptin plasma levels. Finally the investigators hypothesize that taVNS may reduce the impact of obesity on insulin resistance by modulating PAI-1 (plasminogen activator inhibitor-1; increased in obesity and metabolic syndrome), resistin (adipose tissue secretory factor, suggested to link obesity with insulin resistance), vistatin (enriched in visceral fat and may stimulate the insulin receptor), adipsin (secreted from adipocytes; improves β-cell function), and adiponectin (secreted from adipose tissue; increases insulin sensitivity). In normal weight (BMI<25, n=14), overweight (BMI<30, n=14), and obese (BMI>30, n=14) and otherwise healthy study participants blood glucose levels and plasma concentrations (finger prick blood sampling) of insulin, glucagon, C-peptide, GLP-1, GIP, ghrelin, leptin, PAI-1, resistin, vistatin (Bio-Plex kit 171A7001M), adipsin, and adiponectin (Bio-Plex kit 171A7002M) will be determined before and after 30 minutes of taVNS (EMS 7500, 10 Hz, 300ms, n=7 in each body weight group) or sham taVNS (control experiment, n=7 in each body weight group). Before, during and after taVNS or sham taVNS autonomic function will be assessed by heart rate variability analysis from ECG recordings. The investigators expect that the outcome of this study will demonstrate that taVNS lowers blood glucose levels and elicits hormone/adipokine responses consistent with anorexia and improved insulin resistance. The investigators further hypothesize that these effects of taVNS will be more pronounced in obese compared to overweight and normal weight study participants.

Conditions

Diabetes Mellitus, Type 2; Obesity

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Normal Weight

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.

Group Type: EXPERIMENTAL

taVNS

Intervention Type: 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.

Sham taVNS

Intervention Type: 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.

Overweight

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.

Group Type: EXPERIMENTAL

taVNS

Intervention Type: 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.

Sham taVNS

Intervention Type: 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.

Obese

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.

Group Type: EXPERIMENTAL

taVNS

Intervention Type: 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.

Sham taVNS

Intervention Type: 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.

Interventions

taVNS

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.

Intervention Type: DEVICE

Sham taVNS

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.

Intervention Type: DEVICE

Other Intervention Names

Transcutaneous Auricular Vagus Nerve Stimulation; Sham Transcutaneous Auricular Vagus Nerve Stimulation

Eligibility Criteria

Inclusion Criteria

• Generally healthy

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Burrell College of Osteopathic Medicine

OTHER

Sponsor Role: lead

Responsible Party

Harald Stauss

Associate Professor of Pharmacology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Harald M Stauss, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Burrell College of Osteopathic Medicine

Locations

Burrell College of Osteopathic Medicine

Las Cruces, New Mexico, United States

Countries

United States

Other Identifiers

0079_2021

Identifier Type: -

Identifier Source: org_study_id