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Microelectrode Recordings From the Vagus Nerve in Awake Humans

Primary Purpose

Epilepsy

Status
Not yet recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
VNS stimulation and intraneural recordings
Record multi-unit activity from intraneural sites
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Epilepsy

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University of Minnesota
  • 99 Commercial Road

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

VNS

non-VNS participants

Arm Description

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

participants without implanted VNS devices

Outcomes

Primary Outcome Measures

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
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.
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
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
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
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.
Discharge variability of cardiac parasympathetic nerve fibers
Vagal nerve stimulator device. Coefficient of variation, %

Secondary Outcome Measures

Full Information

First Posted
July 10, 2023
Last Updated
September 18, 2023
Sponsor
University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT06016686
Brief Title
Microelectrode Recordings From the Vagus Nerve in Awake Humans
Official Title
Microelectrode Recordings From the Vagus Nerve in Awake Humans
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 1, 2023 (Anticipated)
Primary Completion Date
October 1, 2024 (Anticipated)
Study Completion Date
October 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
VNS
Arm Type
Experimental
Arm Description
participants with surgically implanted VNS electrodes to treat drug-resistant epilepsy
Arm Title
non-VNS participants
Arm Type
Experimental
Arm Description
participants without implanted VNS devices
Intervention Type
Other
Intervention Name(s)
VNS stimulation and intraneural recordings
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Record multi-unit activity from intraneural sites
Intervention Description
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.
Primary Outcome Measure Information:
Title
identify action potential morphology of specific fibers activated by vagal nerve stimulation (VNS)
Description
assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module
Time Frame
4 hours
Title
identify ratio of myelinated fibers in specific fibers activated by vagal nerve stimulation (VNS)
Description
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.
Time Frame
4 hours
Title
physiological identification of the specific fibers activated by vagal nerve stimulation (VNS)
Description
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
Time Frame
4 hours
Title
identify firing rates of the specific fibers activated by vagal nerve stimulation (VNS)
Description
assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. in Hertz
Time Frame
4 hours
Title
identify stimulus current required to activate specific fibers activated by vagal nerve stimulation (VNS)
Description
assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. in milli-amps
Time Frame
4 hours
Title
differences in firing rates of cardiac parasympathetic vagal activity
Description
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.
Time Frame
4 hours
Title
Discharge variability of cardiac parasympathetic nerve fibers
Description
Vagal nerve stimulator device. Coefficient of variation, %
Time Frame
4 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kathryn Vera, PhD
Phone
612-625-5018
Email
giero002@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vaughan G Macefield, PhD
Organizational Affiliation
Monash University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathryn Vera, PhD
Phone
612-625-5018
Email
giero002@umn.edu
Facility Name
99 Commercial Road
City
Prahan Victoria
ZIP/Postal Code
3182
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vaughan G Macefield, BSc(Hons) PhD DSc FAAS
Phone
+61 (0)426 581 647
Email
vaughan.macefield@monash.edu

12. IPD Sharing Statement

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Microelectrode Recordings From the Vagus Nerve in Awake Humans

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