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

NCT06597149 | Recruiting FDA Device

• 1 other identifier: 24300
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out if investigators can stimulate the vagus nerve (a nerve in the body that runs from your brain to the large intestine), and influence insulin, C-peptide, and glucose levels. C-peptide is a substance that is created when insulin is produced and released into the body. The vagus nerve is a largely internal nerve that controls many bodily functions, including stomach function. Investigators hope that by stimulating the vagal nerve using the TeNS behind the ear, this stimulation can affect insulin levels, and this will help innovate treatment of patients with nausea, vomiting, and disordered stomach function, and patients with diabetes. Researchers hope to be able to measure the activity of the vagus nerve when it is stimulated in other ways. This could help investigators learn more about studying this nerve in the future.

Conditions

Healthy

Keywords

Healthy; Individual

Outcome Measures

Primary Outcomes (7)

• Association between acute transcutaneous auricular vagus nerve stimulation and 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.

  one month

• Association between acute transcutaneous auricular vagus nerve stimulation and change in C-peptide levels

  \- Measure description: 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.

  one month

• Association between acute transcutaneous auricular vagus nerve stimulation and 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

  one month

• Association between acute transcutaneous auricular vagus nerve stimulation and 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.

  one month

• 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.

  one month

• 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.

  one month

• 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.

  one month

Secondary Outcomes (3)

• Correlation between gender and changes in circulating plasma insulin levels

  one month

• Correlation between age and changes in circulating plasma insulin levels

  one month

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

  one month

Study Arms (1)

Stimulation

EXPERIMENTAL

Subjects are placed supine, ECG electrodes are applied, a butterfly catheter is inserted into a peripheral vein. A 5 ml sample of blood is withdrawn. A TENS device is placed on the cutaneous branch of the auricular branch of the vagus nerve. After a twenty-minute baseline reading, the TENS unit is then turned ON and electrical stimuli are delivered over 40 minutes. A second sample of blood representing the experimental period is drawn at the end of the 40 minutes. The TENS device is then turned to the OFF positon and after twenty minutes a third and final sample of blood is drawn.

Device: Transcutaneous Auricular Vagus Nerve Stimulation

Interventions

Transcutaneous Auricular Vagus Nerve Stimulation DEVICE

Healthy adult participants will be assigned to either the stimulation group or the sham group. The stimulation group will receive mild stimulation from the TeNS device and the sham group will receive no stimulation but will believe that they are receiving stimulus.

Stimulation

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: NA
• Masking: NONE
• Masking Details: Individuals will be either assigned to either the Active or the Sham groupings. The active group will receive a mild stimulation from the TaVNS device and the sham group will receive no stimulation but will believe that they are receiving a stimulus.
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Healthy adults will receive mild transcutaneous stimulation of the auricular branch of the vagal nerve in order to determine if the stimulation affects plasma insulin levels.

Study Record Dates

• First Submitted: September 9, 2024
• First Posted: September 19, 2024
• Study Start: April 16, 2025
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)