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

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):

1. Group 1: Sham taVNS followed by active taVNS
2. 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.

Study Overview

• Status: Recruiting
• Conditions: Hemostasis; Blood Biomarkers
• Intervention / Treatment: Device: Volta System

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maaryj Ahmad; Phone Number: (516) 562-1505; Email: mahmad11@northwell.edu

Study Locations

• United States
  • New York
    • Manhasset, New York, United States, 11030
      • Recruiting
      • The Feinstein Institutes for Medical Research
      • Contact: Maaryj Ahmad; Phone Number: 516-562-1505; Email: mahmad11@northwell.edu
      • Principal Investigator: Lionel Blanc, PhD
      • Sub-Investigator: Jared Huston, MD, FACS
      • Sub-Investigator: Carlos Bravos-Iniguez, MD, PhD
      • Sub-Investigator: Julien Papoin, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participant is between 18 and 65 years of age
2. Participant is English proficient
3. Participant is able to provide informed consent and function at an intellectual level sufficient for study requirements

Exclusion Criteria:

1. Participant has a history of thrombocytopenia (platelet count <100k)
2. Participant has reported coagulopathy (elevated prothrombin time (PT), elevated partial thromboplastin time (PTT), elevated activated clotting time (ACT))
3. Participant has internal bleeding, external bleeding, easy bruising
4. Participant has a history of abnormal bleeding or blood disorder, including anemia or anemia-related disorders
5. Participant has a history of coagulopathy, including hemophilia, stroke, pulmonary embolism, myocardial infarction, or deep vein thromboses
6. 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
7. 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
8. 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
9. Participant has consumed caffeine within the past 12 hours
10. Participant has received a blood transfusion within 30 days prior to study
11. Participant has a history of epileptic seizures
12. Participant has a history of neurologic diseases or traumatic brain injury
13. Participant has presence of devices (e.g., pacemakers, cochlear prostheses, neurostimulators)
14. Participant has abnormal ear anatomy or ear infection present
15. 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
16. Females who are pregnant, lactating or menstruating
17. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)	Device: Volta System; 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).
Experimental: Transcutaneous Auricular Neurostimulation (tAN)	Device: Volta System; 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).

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)

Collaborators and Investigators

• Sponsor: Five Liters, Inc.
• Collaborators: Northwell Health; The Feinstein Institutes for Medical Research

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: July 14, 2023
• First Submitted That Met QC Criteria: August 2, 2023
• First Posted (Actual): August 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Healthy human; Neurostimulation; Blood biomarkers; Transcutaneous auricular vagus nerve stimulation; Transcutaneous auricular neurostimulation
• Other Study ID Numbers: 5L-BLD-03; 23-0265 (Other Identifier: Northwell Health)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No