Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Obesity and Insulin Resistance
April 26, 2022 updated by: Harald Stauss, Burrell College of Osteopathic Medicine
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
30
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
New Mexico
-
Las Cruces, New Mexico, United States, 88001
- Burrell College of Osteopathic Medicine
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: 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.
|
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.
Other Names:
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.
Other Names:
|
|
Experimental: 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.
|
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.
Other Names:
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.
Other Names:
|
|
Experimental: 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.
|
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.
Other Names:
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in Blood Glucose Concentration induced by taVNS
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the sham taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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
Time Frame: During the taVNS intervention (30 min).
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Changes in Autonomic Function induced by taVNS
Time Frame: During the taVNS intervention (30 min).
|
Autonomic function will be assessed by heart rate variability analysis of ECG recordings obtained before and after application of taVNS.
Changes in autonomic function will be determined by the difference in heart rate variability before and after taVNS (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Changes in Autonomic Function induced by sham taVNS
Time Frame: During the sham taVNS intervention (30 min).
|
Autonomic function will be assessed by heart rate variability analysis of ECG recordings obtained before and after application of sham taVNS.
Changes in autonomic function will be determined by the difference in heart rate variability before and after sham taVNS (after sham taVNS minus before sham taVNS).
|
During the sham taVNS intervention (30 min).
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 14, 2021
Primary Completion (Actual)
April 26, 2022
Study Completion (Actual)
April 26, 2022
Study Registration Dates
First Submitted
June 2, 2021
First Submitted That Met QC Criteria
June 11, 2021
First Posted (Actual)
June 15, 2021
Study Record Updates
Last Update Posted (Actual)
April 28, 2022
Last Update Submitted That Met QC Criteria
April 26, 2022
Last Verified
April 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 0079_2021
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
Yes
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