NCT04926415

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

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Burrell College of Osteopathic Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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

Interventions

Type	Name	Description
DEVICE	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.
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.

Timeline

• Start date: 2021-06-14
• Primary completion: 2022-04-26
• Completion: 2022-04-26
• First posted: 2021-06-15
• Last updated: 2022-04-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study