Microelectrode Recordings From the Vagus Nerve in Awake Humans

NCT06016686 | Recruiting Phase 1

• 1 other identifier: VNS
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Epilepsy

Outcome Measures

Primary Outcomes (7)

• 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

Study Arms (2)

VNS

EXPERIMENTAL

participants with surgically implanted VNS electrodes to treat drug-resistant epilepsy

Other: VNS stimulation and intraneural recordings

non-VNS participants

EXPERIMENTAL

participants without implanted VNS devices

Other: Record multi-unit activity from intraneural sites

Interventions

VNS stimulation and intraneural recordings OTHER

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.

VNS

Record multi-unit activity from intraneural sites OTHER

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.

non-VNS participants

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

MeSH Terms

Conditions

Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Vaughan G Macefield, PhD

  Monash University

  PRINCIPAL INVESTIGATOR

• John Osborn

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kathryn Vera, PhD

CONTACT

612-625-5018; giero002@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2023
• First Posted: August 30, 2023
• Study Start: April 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (1)