Microelectrode Recordings From the Vagus Nerve in Awake Humans

This Anchillary project uses a refined technique of ultrasound-guided microneurography of the human cervical vagus nerve, an approach developed by Professor Vaughan Macefield and used safely to-date in 44 prior study participants.

The overall goal of this project is to build upon prior data obtained using this approach by undertaking a detailed neurophysiological investigation of the human vagus nerve and to identify the nerve fibers activated during vagal nerve stimulation (VNS) in participants with implanted VNS devices in response to different stimulation parameters. In addition to providing data in unprecedented detail into the physiology of the human vagus nerve, this project will investigate different stimulus intensities, durations and frequencies that differentially excite myelinated and unmyelinated nerve fibers. These results will inform the CSP and guide future development of novel neural interfaces for VNS for various clinical applications.

Study Overview

• Status: Recruiting
• Conditions: Epilepsy
• Intervention / Treatment: Other: VNS stimulation and intraneural recordings; Other: Record multi-unit activity from intraneural sites

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kathryn Vera, PhD; Phone Number: 612-625-5018; Email: giero002@umn.edu

Study Locations

• Australia
  • Prahan Victoria, Australia, 3182
    • Recruiting
    • 99 Commercial Road
    • Contact: Vaughan G Macefield, BSc(Hons) PhD DSc FAAS; Phone Number: +61 (0)426 581 647; Email: vaughan.macefield@monash.edu
• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
      • Contact: Kathryn Vera, PhD; Phone Number: 612-625-5018; Email: giero002@umn.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The participant is greater than or equal to (≥)18 years and is less than or equal to (≤) 40 years of age
• English speaking
• Medicare covered or equivalent health insurance from a partner country

Exclusion Criteria:

• Pregnant
• Smokes and is unwilling to abstain from smoking on the day of the experiment.
• Inability or unwillingness to provide written informed consent.
• Individuals with difficulty standing unassisted for 5 minutes during the tilt-table testing
• Individuals found to have a significant carotid artery plaque or intima-media thickness > 1 mm as assessed by ultrasonography during the ultrasound-screening steps of the study visit
• Vagus nerve not visible on ultrasound
• VNS electrodes are not in a suitable location to allow for microelectrode insertion
• Any other clinical reasons deemed by the investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VNS; participants with surgically implanted VNS electrodes to treat drug-resistant epilepsy	Other: VNS stimulation and intraneural recordings; A minimum of three stimulation frequencies (1, 10 and 30 Hz), each up to 60s in duration, will be delivered via the VNS device. Intraneural recordings proximal or distal to the VNS electrodes during delivery of VNS will be performed. Approximately two to five fascicles will be explored in each nerve.
Experimental: non-VNS participants; participants without implanted VNS devices	Other: Record multi-unit activity from intraneural sites; Perform a more detailed vagal nerve mapping study by recording from single nerve fibers, including those fibers supplying the heart, lungs, airways and other end-organs. The investigators shall perform functional mapping of the left and right vagus nerves, such as those with cardiac-related and/or respiratory-related neural activity. The research team will also record activity from other nearby fibers to map the differences in neurological behavior in fascicles that control the heart, lungs, airways and other systems.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
identify action potential morphology of specific fibers activated by vagal nerve stimulation (VNS)	assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module	4 hours
identify ratio of myelinated fibers in specific fibers activated by vagal nerve stimulation (VNS)	assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. Whether a nerve fiber is (un)myelinated can be determined by visual inspection. Myelinated fibers typically produce "a positive-going narrow spike profile.	4 hours
physiological identification of the specific fibers activated by vagal nerve stimulation (VNS)	assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. use of tracing and nerve recordings analysis to identify the types of nerves	4 hours
identify firing rates of the specific fibers activated by vagal nerve stimulation (VNS)	assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. in Hertz	4 hours
identify stimulus current required to activate specific fibers activated by vagal nerve stimulation (VNS)	assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. in milli-amps	4 hours
differences in firing rates of cardiac parasympathetic vagal activity	compare any changes in parasympathetic vagal activity with participants who have not been implanted with a vagal nerve stimulator (Non-VNS Participants). Labchart; spike histogram module. Unit: Hz.	4 hours
Discharge variability of cardiac parasympathetic nerve fibers	Vagal nerve stimulator device. Coefficient of variation, %	4 hours

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Vaughan G Macefield, PhD, Monash University; Principal Investigator: John Osborn, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: July 10, 2023
• First Submitted That Met QC Criteria: August 28, 2023
• First Posted (Actual): August 30, 2023

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: VNS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No