Effect of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on Plasma Insulin Levels

NCT06597149 | Recruiting FDA Device

• 1 other identifier: 24300
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The vagus or vagal nerve is a nerve that sends signals from the brain to other parts of the body to control involuntary functionm, including stomach function, and it is important to the regulation of insulin, C-peptide, and glucose levels. The purpose of this study is to evaluate whether electrically stimulating the nerve around the external ear will also stimulate the internal vagus nerve and influence the levels of insulin, C-peptide, and glucose. If it does, investigators hope that this will help innovate treatment of patients with nausea, vomiting, and disordered stomach function, and patients with diabetes.

Conditions

Healthy

Keywords

Healthy; Individual

Outcome Measures

Primary Outcomes (7)

• Change in plasma insulin levels

  Repeated measures analysis of variance will be used to determine the effects of stimulation period (baseline, end of stimulation, end of non-stimulation) and active/control group on plasma insulin levels.

  Study Days 1 and 2

• Change in C-peptide levels

  Repeated measures analysis of variance will be used to determine the effects of stimulation period (baseline, end of stimulation, end of non-stimulation) and active/control group on C-peptide levels.

  Study Days 1 and 2

• Change in glucose levels

  Repeated measures analysis of variance will be used to determine the effects of stimulation period (baseline, end of stimulation, end of non-stimulation) and active/control group on glucose levels

  Study Days 1 and 2

• Change in heart rate variability

  Repeated measures analysis of variance will be used to determine the effects of stimulation period (baseline, end of stimulation, end of non-stimulation) and active/control group on heart rate variability.

  Study Days 1 and 2

• Association between changes in heart rate variability and plasma insulin levels

  Pearson's correlation coefficients will be used to evaluate the association between change in heart rate variability (end of stimulation minus baseline) with changes in plasma insulin levels (end of stimulation minus baseline). Heart rate variability will be used as an indication of changes in parasympathetic or sympathetic activation.

  Study Days 1 and 2

• Association between changes in heart rate variability and C-peptide levels

  Pearson's correlation coefficients will be used to evaluate the association between change in heart rate variability (end of stimulation minus baseline) with changes in C-peptide levels (end of stimulation minus baseline). Heart rate variability will be used as an indication of changes in parasympathetic or sympathetic activation.

  Study Days 1 and 2

• Association between changes in heart rate variability and glucose levels

  Pearson's correlation coefficients will be used to evaluate the association between change in heart rate variability (end of stimulation minus baseline) with changes in glucose levels (end of stimulation minus baseline). Heart rate variability will be used as an indication of changes in parasympathetic or sympathetic activation.

  Study Days 1 and 2

Secondary Outcomes (3)

• Correlation between gender and changes in circulating plasma insulin levels

  Study Days 1 and 2

• Correlation between age and changes in circulating plasma insulin levels

  Study Days 1 and 2

• Correlation between body mass index and changes in circulating plasma insulin levels

  Study Days 1 and 2

Study Arms (2)

Active Stimulation, then No electrodes

EXPERIMENTAL

After an initial baseline blood sample is drawn, a TENS unit electrode clip will be placed on the inside of the outer ear and vagal nerve recordings are initiated. After 20 minutes of baseline recording, a second blood sample is drawn, after which, the TENS unit is turned ON for 40 minutes of stimulation. At the end of the stimulation period, a third blood sample is drawn and the TENS device is then turned OFF. After 20 minutes of recovery, a fourth and final sample of blood is drawn. Vagal nerve activity recordings are continued until the final blood sample is drawn. Subjects will be asked to return for an additional visit during which the TENS unit will not be placed, but the same vagal nerve recordings and blood draws will be obtained.

Device: Transcutaneous Auricular Vagus Nerve Stimulation

Sham Stimulation, then No Electrodes

SHAM COMPARATOR

After an initial baseline blood sample is drawn, a TENS unit electrode clip will be placed on the inside of the outer ear, but will not be turned on. Vagal nerve recordings will be initiated. After 20, 60 and 80 minutes, additional blood samples are drawn. Vagal nerve activity recordings are continued until the final blood sample is drawn. Subjects will be asked to return for an additional visit during which the TENS unit will not be placed, but the same vagal nerve recordings and blood draws will be obtained.

Device: Sham Procedure (No Stimulation)

Interventions

Transcutaneous Auricular Vagus Nerve Stimulation DEVICE

For participants in the active stimulation group, electrical stimuli are delivered continuously for 40 minutes at a pulse width of 300 microseconds, pulse frequency of 25 Hz, and pulse amplitude of 0.5 to 1.5 mA based on the tolerance of the patient. Stimuli current and frequency may be decreased, if necessary, to minimize participant discomfort.

Active Stimulation, then No electrodes

Sham Procedure (No Stimulation) DEVICE

The TENS device will be placed but not turned on.

Sham Stimulation, then No Electrodes

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy Volunteers
• Aged 18-70
• Willing to have ECG electrodes placed on their neck and chest areas.
• Willing to have electrodes placed in the external ear.
• Willing to have an indwelling catheter placed to avoid multiple sticks for blood draw.

You may not qualify if:

• Unable to provide consent.
• Diabetes diagnosis per patient report
• Having known allergies to adhesive on electrode pads or bandages
• Having gastric motility issues as determined by the PI or clinical coordinator.
• Taking any medications that may affect gastric motility or cardiac variability, i.e. alpha or beta blockers for hypertension.
• Pregnant females
• Those unwilling to have the taVNS device placed in their ear.
• Those unwilling to consent to a blood draw.
• Prisoners

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University Hospital

Indianapolis, Indiana, 46202, United States

RECRUITING

Related Publications (9)

• van der Voort IR, Becker JC, Dietl KH, Konturek JW, Domschke W, Pohle T. Gastric electrical stimulation results in improved metabolic control in diabetic patients suffering from gastroparesis. Exp Clin Endocrinol Diabetes. 2005 Jan;113(1):38-42. doi: 10.1055/s-2004-830525.

  PMID: 15662594 BACKGROUND

• Huang F, Dong J, Kong J, Wang H, Meng H, Spaeth RB, Camhi S, Liao X, Li X, Zhai X, Li S, Zhu B, Rong P. Effect of transcutaneous auricular vagus nerve stimulation on impaired glucose tolerance: a pilot randomized study. BMC Complement Altern Med. 2014 Jun 26;14:203. doi: 10.1186/1472-6882-14-203.

  PMID: 24968966 BACKGROUND

• Vosseler A, Zhao D, Fritsche L, Lehmann R, Kantartzis K, Small DM, Peter A, Haring HU, Birkenfeld AL, Fritsche A, Wagner R, Preissl H, Kullmann S, Heni M. No modulation of postprandial metabolism by transcutaneous auricular vagus nerve stimulation: a cross-over study in 15 healthy men. Sci Rep. 2020 Nov 24;10(1):20466. doi: 10.1038/s41598-020-77430-2.

  PMID: 33235256 BACKGROUND

• Kozorosky EM, Lee CH, Lee JG, Nunez Martinez V, Padayachee LE, Stauss HM. Transcutaneous auricular vagus nerve stimulation augments postprandial inhibition of ghrelin. Physiol Rep. 2022 Apr;10(8):e15253. doi: 10.14814/phy2.15253.

  PMID: 35441808 BACKGROUND

• Yin J, Ji F, Gharibani P, Chen JD. Vagal Nerve Stimulation for Glycemic Control in a Rodent Model of Type 2 Diabetes. Obes Surg. 2019 Sep;29(9):2869-2877. doi: 10.1007/s11695-019-03901-9.

  PMID: 31222497 BACKGROUND

• Payne SC, Ward G, Fallon JB, Hyakumura T, Prins JB, Andrikopoulos S, MacIsaac RJ, Villalobos J. Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model. Physiol Rep. 2022 Apr;10(8):e15257. doi: 10.14814/phy2.15257.

  PMID: 35439355 BACKGROUND

• Hampton RF, Jimenez-Gonzalez M, Stanley SA. Unravelling innervation of pancreatic islets. Diabetologia. 2022 Jul;65(7):1069-1084. doi: 10.1007/s00125-022-05691-9. Epub 2022 Mar 29.

  PMID: 35348820 BACKGROUND

• Zhu Y, Xu F, Lu D, Rong P, Cheng J, Li M, Gong Y, Sun C, Wei W, Lin L, Chen JDZ. Transcutaneous auricular vagal nerve stimulation improves functional dyspepsia by enhancing vagal efferent activity. Am J Physiol Gastrointest Liver Physiol. 2021 May 1;320(5):G700-G711. doi: 10.1152/ajpgi.00426.2020. Epub 2021 Feb 24.

  PMID: 33624527 BACKGROUND

• Krasaelap A, Sood MR, Li BUK, Unteutsch R, Yan K, Nugent M, Simpson P, Kovacic K. Efficacy of Auricular Neurostimulation in Adolescents With Irritable Bowel Syndrome in a Randomized, Double-Blind Trial. Clin Gastroenterol Hepatol. 2020 Aug;18(9):1987-1994.e2. doi: 10.1016/j.cgh.2019.10.012. Epub 2019 Oct 14.

  PMID: 31622740 BACKGROUND

Study Officials

• Thomas V Nowak, MD

  IU Medical Scool

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maureen Schilling, BS

CONTACT

3172782064; maschi@iu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Individuals will be either assigned to either the Active or the Sham groupings. Both groups will have the device placed at Visit 1, but only the active group will receive stimulation. Participants are blinded to which group they are in.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 9, 2024
• First Posted: September 19, 2024
• Study Start: April 21, 2025
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: October 1, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)