Clinical trial NCT06597149: Effect of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on Plasma Insulin Levels
Official title: Effect of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on Plasma Insulin Levels
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Healthy
Keywords: Healthy
Individual
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: OTHER

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.

Detailed description: STUDY OBJECTIVES

Primary: The research described in this protocol is best described as an extension of the researcher's current protocol which is designed to measure cervical compound vagal nerve action potentials in patients who have an implanted gastric electrical stimulation device (GESD). The difference is that only healthy volunteer subjects will be recruited and studied, and rather than undergoing gastric electrical stimulation (GES), volunteer subjects will undergo transcutaneous stimulation of the auricular branch of the vagus nerve (taVNS) to determine whether this modality will also influence plasma insulin, C-peptide and glucose levels. While not a part of the current proposal; if the results of this study are promising we anticipate applying electrical stimulation of the ABVN in future studies of gastroparetic patients with symptomatic nausea and vomiting.

Secondary/exploratory: If taVNS proves to have an effect on circulating plasma insulin levels, then a secondary component of this study is to determine which subject variables (age, gender, BMI) may influence this response. While not formally a part of this proposal, investigators anticipate future studies will be designed to determine the optimal stimulus parameters (stimulus current, frequency, pulse duration) needed to produce this effect. Researchers' previous investigation using percutaneous electrical nerve field stimulation (PENFS) have shown that this modality affects the sympathetic and parasympathetic controls or heart rate variability. The current proposal will also determine whether the same effect occurs with transcutaneous auricular vagus nerve stimulation (taVNS).

SPECIFIC AIM 1:

To determine if acute taVNS stimulation of the cymba concha area of the external ear in human subjects affects plasma insulin, C-peptide, and glucose levels.

Investigators' preliminary studies show that electrical stimuli applied to electrodes implanted in the serosa of the stomach augment plasma insulin levels in humans. Presumably this is due activation of sympathetic and parasympathetic nerves which also innervate the pancreas. Researchers propose to non-invasively access the vagus nerve by applying electrical stimuli to the cymba concha area of the human external ear. This area is innervated by the cutaneous branch of the vagus nerve which, in turn, sends branches to the sensory nucleus of the vagus nerve, the nucleus tractus solitarius, which then sends nerve fibers throughout the brainstem to control autonomic function throughout the autonomic nervous system.

SPECIFIC AIM 2:

To determine if acute taVNS of the cymba concha area of the external ear affects heart rate variability in human subjects.

Heart rate variability is governed by parasympathetic and sympathetic nerves. By using frequency-domain and time domain analysis it is possible to determine whether 1) taVNS activates the auricular branch of the vagus nerve, and 2) whether any observed effects are mediated through the parasympathetic and/or sympathetic autonomic nervous system.

SPECIFIC AIM 3:

To determine if the changes in plasma insulin, C-peptide, or glucose levels are associated with corresponding changes in parasympathetic or sympathetic activation.

By using frequency-domain and time-domain analysis of heart rate variability it is possible to determine whether any observed changes are due to activation of parasympathetic or sympathetic nervous system or a combination of both. Some subjects may show a greater change in plasma insulin, C-peptide or glucose levels than others during taVNS. Researchers propose to determine whether these changes are mirrored by corresponding alterations in parasympathetic and sympathetic nervous system activity.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Unable to provide consent.
* Diabetes diagnosis per patient report
* Having known allergies to adhesive on electrode pads or bandages
* Self -report of diagnosis of gastric motility issues
* 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

Primary outcomes:
measure: Association between acute transcutaneous auricular vagus nerve stimulation and change in plasma insulin levels
timeFrame: one month
measure: Association between acute transcutaneous auricular vagus nerve stimulation and change in C-peptide levels
timeFrame: one month
measure: Association between acute transcutaneous auricular vagus nerve stimulation and change in glucose levels
timeFrame: one month
measure: Association between acute transcutaneous auricular vagus nerve stimulation and heart rate variability
timeFrame: one month
measure: Association between changes in heart rate variability and plasma insulin levels
timeFrame: one month
measure: Association between changes in heart rate variability and C-peptide levels
timeFrame: one month
measure: Association between changes in heart rate variability and glucose levels
timeFrame: one month
Secondary outcomes:
measure: Correlation between gender and changes in circulating plasma insulin levels
timeFrame: one month
measure: Correlation between age and changes in circulating plasma insulin levels
timeFrame: one month
measure: Correlation between body mass index and changes in circulating plasma insulin levels
timeFrame: one month
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Hospital
state: Indiana
Study officials:
affiliation: IU Medical Scool
name: Thomas V Nowak, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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citation: 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.
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