Systematic Evaluation of VNS Parameters

Epilepsy Clinical Trial

Official title:

Systematic Evaluation of Vagus Nerve Stimulation Parameters on Cardiac Rhythm, Laryngeal Muscle Electromyography, and Vagus Nerve Activation in Acute and Chronic Implantations

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05395026
• Other study ID #: Pro00103473
• Status: Enrolling by invitation
• Phase: N/A
• Start date: November 28, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to measure the activation of the vagus nerve and the side effects of vagus nerve stimulation (VNS) (neck muscle contractions, changes in heart rate) across a range of stimulation parameters typically used in VNS therapy for epilepsy (pulse durations, pulse amplitudes, pulse repetition rates). This mapping of the parameter space may inform future device programming to improve electrical activation of the vagus nerve and/or to reduce side effects, and it may be used for validation of computational models. The study will recruit adult participants with epilepsy who are undergoing surgery either for an initial implant of a VNS device or for replacement of the implanted pulse generator (IPG) due to battery depletion. During surgery, the study will involve stimulating the vagus nerve via the standard implanted clinical VNS electrodes over a range of stimulation parameters while recording the activity of the vagus nerve (electroneurogram (ENG)), electromyogram (EMG) response of neck/throat muscles, and the heart rate (electrocardiogram (EKG)). Stimulation parameters will be within the ranges used for clinical therapy and below limits established for non-damaging electrical stimulation.

Description:

This study will recruit adult participants with epilepsy who are undergoing planned surgery either for an initial implant of a vagus nerve stimulation (VNS) device or for replacement of their VNS implanted pulse generator (IPG) due to battery depletion. The primary study goals are to measure the activation of the vagus nerve and the side effects of vagus nerve stimulation (neck muscle contractions, changes in heart rate) across a range of stimulation parameters typically used in VNS therapy for epilepsy. This mapping of the parameter space may inform future device programming to improve electrical activation of the vagus nerve and/or to reduce side effects. All study participants will be assigned to a single study group and will complete the same study procedures.

The research study will take place during VNS surgery. For participants undergoing a first VNS implant surgery, once the vagus nerve is exposed and before placing the VNS electrodes, the investigators may image the nerve with ultrasound. Mapping of the parameter space will then occur after placement of the cuff electrodes around the cervical vagus nerve for participants undergoing a first VNS implant surgery or removal of the IPG with the depleted battery for patients undergoing IPG replacement surgery. Temporary sterile extension wires will connect the implanted VNS electrode to the research stimulation system. Research procedures will involve stimulating the vagus nerve through the standard implanted clinical VNS electrodes over a range of stimulation parameters. At the same time, the investigators will record how changes in stimulation affect the activity of the vagus nerve (measured by electroneurogram (ENG)), the response of the neck and throat muscles (by electromyogram (EMG)) and the heart rate (by electrocardiogram (EKG)). Several stimulation trials will be conducted with different VNS parameters (pulse duration, pulse amplitude, and pulse repetition rate) delivered in randomized order. Stimulation parameters will be within the ranges used for clinical therapy and will not exceed those that produce a 25% reduction in heart rate. Measurements will be made during 10 to 60 second trials, in which stimulation will be off for the first section (baseline), on for the second section (responses to stimulation), and off for the final section (recovery). The stimulus waveform will be a charge-balanced biphasic pulse, with values of charge density (D) limited to values below the nondamaging limits that are well-established in literature.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 30
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• adult epilepsy patients undergoing VNS electrode implantation or implanted pulse generator (IPG) replacement surgery

• in good health

• neurologically stable aside from epilepsy

• able to provide informed consent

Exclusion Criteria:

• patients with another implanted electrical device (besides VNS)

• a history of heart conditions that the surgeon considers a contraindication to study participation

Related Conditions & MeSH terms

• Epilepsy

Intervention

Other:
• electrical stimulation of vagus nerve
VNS electrical stimulation parameters (pulse duration, pulse amplitude, and pulse frequency) will be systematically changed to determine the effect on vagus nerve activation, laryngeal muscle contraction, and heart rate.

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

References & Publications (2)

Cogan SF, Ludwig KA, Welle CG, Takmakov P. Tissue damage thresholds during therapeutic electrical stimulation. J Neural Eng. 2016 Apr;13(2):021001. doi: 10.1088/1741-2560/13/2/021001. Epub 2016 Jan 20. — View Citation

Kumsa D, Steinke GK, Molnar GF, Hudak EM, Montague FW, Kelley SC, Untereker DF, Shi A, Hahn BP, Condit C, Lee H, Bardot D, Centeno JA, Krauthamer V, Takmakov PA. Public Regulatory Databases as a Source of Insight for Neuromodulation Devices Stimulation Parameters. Neuromodulation. 2018 Feb;21(2):117-125. doi: 10.1111/ner.12641. Epub 2017 Aug 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	stimulation amplitude threshold	The stimulation amplitude threshold is the amplitude when vagus nerve stimulation (VNS) activates the laryngeal muscles and has potential to cause subject discomfort during stimulation. The stimulation amplitude threshold will be measured with the NIM-EMG endotracheal tube recording, and the threshold will be determined as the amplitude that causes the first evoked potential in the laryngeal muscles.	During procedure (30 minutes)