Delivering Transcutaneous Auricular Neurostimulation to Regulate Platelet Activity in Healthy Human Subjects

Study Overview
=================
Brief Summary
-----------------
This study is designed as a randomized, double-blind, sham-controlled, single-center research study in which healthy adults will be randomized 1:1 into one of two experimental groups, to receive transcutaneous auricular vagus nerve stimulation (taVNS) targeting either the auricular branch of the vagus nerve (ABVN) or tAN, which targets the ABVN and the auriculotemporal nerve (ATN): Group 1: Sham taVNS followed by active taVNS Group 2: Sham tAN followed by active tAN Participants will receive 30 minutes of sham stimulation (taVNS or tAN), followed by active stimulation (taVNS or tAN). Blood biomarkers (local and systemic) will be measured before and at several timepoints after stimulation to measure the molecular and cellular effects of the device.

Official Title
-----------------
Delivering Transcutaneous Auricular Neurostimulation to Regulate Platelet Activity in Healthy Human Subjects

Conditions
-----------------
Hemostasis, Blood Biomarkers

Intervention / Treatment
-----------------
* Device: Volta System


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant is between 18 and 65 years of age Participant is English proficient Participant is able to provide informed consent and function at an intellectual level sufficient for study requirements Exclusion Criteria: Participant has a history of thrombocytopenia (platelet count <100k) Participant has reported coagulopathy (elevated prothrombin time (PT), elevated partial thromboplastin time (PTT), elevated activated clotting time (ACT)) Participant has internal bleeding, external bleeding, easy bruising Participant has a history of abnormal bleeding or blood disorder, including anemia or anemia-related disorders Participant has a history of coagulopathy, including hemophilia, stroke, pulmonary embolism, myocardial infarction, or deep vein thromboses Participant has a history of conditions that can cause coagulopathic conditions, including atrial fibrillation, heart valve surgery or replacement, hip or knee replacement, or clotting disorders Participants using coagulation- or platelet-modifying therapies such as clotting factor products, emicizumab, desmopressin acetate, epsilon amino caproic acid, heparin and its derivatives, argatroban, desirudin, bivalirudin, warfarin, dabigatran, apixaban, edoxaban, betrixaban, or aspirin Participant has a history of chronic tobacco use or has ingested nicotine via smoking, vaping, smokeless tobacco, or nicotine patches in the past three months Participant has consumed caffeine within the past 12 hours Participant has received a blood transfusion within 30 days prior to study Participant has a history of epileptic seizures Participant has a history of neurologic diseases or traumatic brain injury Participant has presence of devices (e.g., pacemakers, cochlear prostheses, neurostimulators) Participant has abnormal ear anatomy or ear infection present Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study Females who are pregnant, lactating or menstruating Participant has any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants are risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized into two 30-minute stimulation sessions. One session will be active and the other sham. Participants are blinded to treatment group as well as the stimulation session.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)<br> | Device: Volta System<br>* The Volta System is a wearable, battery-operated, neurostimulation system designed to deliver tAN or taVNS. The device will be used to deliver two 30-minute sessions of active or sham therapy according to the participant's randomization group (taVNS or tAN).<br>|
| Experimental: Transcutaneous Auricular Neurostimulation (tAN)<br> | Device: Volta System<br>* The Volta System is a wearable, battery-operated, neurostimulation system designed to deliver tAN or taVNS. The device will be used to deliver two 30-minute sessions of active or sham therapy according to the participant's randomization group (taVNS or tAN).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker of hemostasis (tissue anti-thrombin (TAT) complex) in blood shed from fingerstick | Mean TAT levels in shed blood after active stimulation versus sham stimulation within each group | From collection up to 240 minutes, assessed upon receipt of assay results (up to one month) | 
| Biomarker of hemostasis (tissue anti-thrombin (TAT) complex) in blood shed from fingerstick | Percent change in TAT levels in shed blood after active stimulation between groups (taVNS vs tAN) | From collection up to 240 minutes, assessed upon receipt of assay results (up to one month) | 
| Biomarkers of hemostasis (TAT complex, D-dimer, viscoelasticity, coagulation tests (prothrombin time (PT), partial thromboplastin time (PTT)) in circulating blood | Mean coagulation biomarker levels in circulating blood after active stimulation versus sham stimulation within each group | From collection up to 240 minutes, assessed upon receipt of assay results (up to one month) | 
| Biomarkers of hemostasis (TAT complex, D-dimer, viscoelasticity, coagulation tests (prothrombin time (PT), partial thromboplastin time (PTT)) in circulating blood | Percent change in coagulation biomarker levels in circulating blood after active stimulation between groups ( taVNS vs tAN) | From collection up to 240 minutes, assessed upon receipt of assay results (up to one month) | 
| Biomarkers of inflammation (tumor necrosis factor (TNF), and interleukin (IL)-1B and IL-6) in circulating whole blood stimulated ex vivo with lipopolysaccharide (LPS) | Mean inflammation biomarker levels in LPS-stimulated whole blood after active stimulation versus sham stimulation within each group | From collection up to 240 minutes, assessed upon receipt of assay results (up to one month) | 
| Biomarkers of inflammation (tumor necrosis factor (TNF), and interleukin (IL)-1B and IL-6) in circulating whole blood stimulated ex vivo with lipopolysaccharide (LPS) | Percent change in inflammation biomarker levels in LPS-stimulated whole blood after active stimulation between groups (taVNS vs tAN) | From collection up to 240 minutes, assessed upon receipt of assay results (up to one month) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Blood biomarkers, Transcutaneous auricular neurostimulation, Transcutaneous auricular vagus nerve stimulation, Neurostimulation, Healthy human