Clinical trial NCT04926415: Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Obesity and Insulin Resistance
Official title: Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Obesity and Insulin Resistance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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
Lead sponsor: Burrell College of Osteopathic Medicine
Sponsor class: OTHER
First posted: 2021-06-15
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Change in Blood Glucose Concentration induced by taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Blood Glucose Concentration induced by sham taVNS
timeFrame: During the sham taVNS intervention (30 min).
measure: Change in Insulin Plasma Concentration induced by taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Insulin Plasma Concentration induced by sham taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Glucagon Plasma Concentration induced by taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Glucagon Plasma Concentration induced by sham taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in C-Peptide Plasma Concentration induced by taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in C-Peptide Plasma Concentration induced by sham taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in GLP-1 Plasma Concentration induced by taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in GLP-1 Plasma Concentration induced by sham taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in GIP Plasma Concentration induced by taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in GIP Plasma Concentration induced by sham taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Ghrelin Plasma Concentration induced by taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Ghrelin Plasma Concentration induced by sham taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Leptin Plasma Concentration induced by taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Leptin Plasma Concentration induced by sham taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in PAI-1 Plasma Concentration induced by taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in PAI-1 Plasma Concentration induced by sham taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Resistin Plasma Concentration induced by taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Resistin Plasma Concentration induced by sham taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Vistatin Plasma Concentration induced by taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Vistatin Plasma Concentration induced by sham taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Adipsin Plasma Concentration induced by taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Adipsin Plasma Concentration induced by sham taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Adiponectin Plasma Concentration induced by taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Change in Adiponectin Plasma Concentration induced by sham taVNS
timeFrame: During the taVNS intervention (30 min).
Secondary outcomes:
measure: Changes in Autonomic Function induced by taVNS
timeFrame: During the taVNS intervention (30 min).
measure: Changes in Autonomic Function induced by sham taVNS
timeFrame: During the sham taVNS intervention (30 min).
Other outcomes:
Locations:
city: Las Cruces
country: United States
facility: Burrell College of Osteopathic Medicine
state: New Mexico
Study officials:
affiliation: Burrell College of Osteopathic Medicine
name: Harald M Stauss, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: