An interventional study of Transcutaneous Auricular Vagus Nerve Stimulation and Sham Procedure (No Stimulation) in Healthy, sponsored by Indiana University. Recruiting at 1 site in United States. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-01.
Sponsored by Indiana University · Not applicable, Interventional, and Other
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.
Healthy volunteer subjects will be recruited for this project, which will be completed at a up to 2 study visits.
Prior to each visit, participants will be asked not to eat or drink anything (except a small amount of water to take medications) for 8-10 hours.
When participants arrive to Study Visit 1, they will be asked to lie in a supine position and will be fitted with:
After the ECG electrodes are placed and the butterfly needle catheter is inserted, the first of 4 blood samples will be collected. The TENS unit clip will then be placed (after cleaning the left ear with an alcohol wipe) and a 20 minute baseline recording will be made, followed by the collection of a second blood sample.
Participants will then undergo their randomly assigned experimental condition (either active stimulation delivered via the TENS device, or no stimulation) for 40 minutes. At the end of the experimental period, a third blood sample is collected and the TENS device is turned off (for participants in the active stimulation group). Participants will then continue to lie on their back for an additional 20 minutes of recovery, after which the fourth and final blood sample is collected. The TENS clip is then removed and the study visit is complete.
Continuous vagal nerve and ECG recordings are obtained during the baseline, experimental, and recovery periods.
Participants will be asked if they wish to return for a second study visit, at which no TENS clip will be placed but the remaining Visit 1 procedures will be repeated.
Indiana University is the lead sponsor of 958 studies on the registry; 200 are open to participants now.
Of its 142 completed or terminated interventional studies of FDA-regulated products, 112 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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
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)
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.
The TENS device will be placed but not turned on.
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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Study Days 1 and 2
Correlation between gender and changes in circulating plasma insulin levels
Pearson's correlation coefficient will be calculated for the association between change in circulating plasma insulin levels (end of stimulation minus baseline) and patient gender.
Time frame: Study Days 1 and 2
Correlation between age and changes in circulating plasma insulin levels
Pearson's correlation coefficient will be calculated for the association between change in circulating plasma insulin levels (end of stimulation minus baseline) and patient age.
Time frame: Study Days 1 and 2
Correlation between body mass index and changes in circulating plasma insulin levels
Pearson's correlation coefficient will be calculated for the association between change in circulating plasma insulin levels (end of stimulation minus baseline) and patient body mass index.
Time frame: Study Days 1 and 2
Plan to share: No — The blood samples collected will be processed in the CRC lab to obtain blood serum. This serum will then be transferred to Dr. Robert Considine at the Indiana University Center for Diabetes and Metabolic Diseases. These samples will only be identified with the study subject number and which blood draw number (1,2,3) the vial contains. ECG recordings are digitized and downloaded to a computer and are analyzed using heart rate variability software (LABVIEW, AD Instruments, Boston, MA). This software contains no references to any person and only contains the subject number for the study.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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