Microelectrode Recordings From the Vagus Nerve in Awake Humans

Phase 1

Recruiting

• Conditions: Epilepsy
• Interventions: Other: Record multi-unit activity from intraneural sites; Other: VNS stimulation and intraneural recordings

• Registration Number: NCT06016686
• Lead Sponsor: University of Minnesota

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-07-10
• Study First Submitted QC: 2023-08-28
• Study First Posted: 2023-08-30
• Study Start: 2024-04-01
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-20
• Last Update Posted: 2025-04-22
• Primary Completion: 2026-04-01
• Study Completion: 2026-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
non-VNS participants	Record multi-unit activity from intraneural sites	participants without implanted VNS devices
VNS	VNS stimulation and intraneural recordings	participants with surgically implanted VNS electrodes to treat drug-resistant epilepsy

Primary Outcome Measures

Name	Time	Method
identify action potential morphology of specific fibers activated by vagal nerve stimulation (VNS)	4 hours	assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module
physiological identification of the specific fibers activated by vagal nerve stimulation (VNS)	4 hours	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
identify stimulus current required to activate specific fibers activated by vagal nerve stimulation (VNS)	4 hours	assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. in milli-amps
differences in firing rates of cardiac parasympathetic vagal activity	4 hours	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.
Discharge variability of cardiac parasympathetic nerve fibers	4 hours	Vagal nerve stimulator device. Coefficient of variation, %
identify firing rates of the specific fibers activated by vagal nerve stimulation (VNS)	4 hours	assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. in Hertz
identify ratio of myelinated fibers in specific fibers activated by vagal nerve stimulation (VNS)	4 hours	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.

Trial Locations

Locations (2)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

99 Commercial Road; 🇦🇺 Prahan Victoria, Australia