Vagal Nerve Stimulation to Reduce Inflammation and Hyperadrenergia

A Study of Safety and Autonomic Responses to Non-Invasive Vagal Stimulation in Persons With Spinal Cord Injury and Non-Disabled Controls Both With and Without Inflammatory Stress

The purpose of this research device study is to learn more about the autonomic nervous system. This system uses nerves to send information from the brain to the rest of the body by electrical signaling and has two divisions, the sympathetic and the parasympathetic branches. It has been thought that electrical stimulation devices could be used to restore balance to the nervous system. Because most of the imbalance seems to happen due to too much sympathetic activity, the investigator plans to focus on the parasympathetic branch. Specifically, the investigator hopes to restore balance by targeting the vagus nerve, which is the main communicator of the parasympathetic branch. The study will examine whether the investigator can decrease sympathetic activity and chronic inflammation by increasing parasympathetic activity. This is a device study that will examine the use of non-invasive vagal nerve stimulation to attenuate inflammatory stress and sympathetic hyperactivity in persons with Spinal Cord Injury and Non-Disabled Controls.

Study Overview

• Status: Withdrawn
• Conditions: Spinal Cord Injury
• Intervention / Treatment: Device: InTENsity MicroCombo

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • The Miami Project to Cure Paralysis/ University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Group 1 & 2:

Inclusion Criteria:

1. Age 18-65
2. Willingness to participate in the study

Exclusion Criteria:

1. Use of an active electrical implant, such as a cardiac pacemaker or cochlear implant
2. Use of a hearing aid in the left ear
3. Use of an implanted insulin or morphine (pain) pump
4. Self-reported history of syncope from known or unknown origins
5. Self-reported history of cardiovascular disease or dysfunction (e.g., cardiovascular disease, arrhythmia, congestive heart failure, or stroke)

Group 3:

Inclusion Criteria:

1. Age 18-65
2. Overweight, with a BMI ≥ 27
3. Presence of chronic inflammation, with C-reactive protein values > 3 mg/l
4. Willingness to participate in the study

Exclusion Criteria:

1. Use of an active electrical implant, such as a cardiac pacemaker or cochlear implant
2. Use of a hearing aid in the left ear
3. Use of an implanted insulin or morphine (pain) pump
4. Self-reported history of syncope from known or unknown origins
5. Self-reported history of cardiovascular disease or dysfunction (e.g., cardiovascular disease, arrhythmia, congestive heart failure, or stroke)
6. Use of statin drugs

Group 4:

Inclusion Criteria:

1. Age 18-65
2. ≥ 1-year post-injury
3. Bladder management by clean intermittent catheterization
4. Spinal cord injury resulting in Paraplegia level T1 to T6 and motor-complete (AIS A or B) impairment. Injury level and impairment will be confirmed by an ASIA exam conducted less than 2 years before study entry. If longer than 2 years, we will have a certified rater repeat the exam.
5. Participant report of symptoms related to autonomic dysreflexia during episodes of full bladder or voiding, including elevated BP, mild headache, paresthesia, chills, nasal congestion, flushing of the skin, or diaphoresis.
6. Willingness to participate in the study.

Exclusion Criteria:

1. Currently hospitalized
2. American Spinal Injury Association (AIS) C-E
3. Currently using an insulin, morphine (pain), or intrathecal pump
4. Use of an active electrical implant, such as a cardiac pacemaker or cochlear implant
5. Use of a hearing aid in the left ear
6. Self-reported history of syncope from known or unknown origins
7. Self-reported history of cardiovascular disease or dysfunction (e.g., cardiovascular disease, arrhythmia, congestive heart failure, or stroke)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Low Hertz; Participants will receive 10 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session. Device: InTENsity MicroCombo	Device: InTENsity MicroCombo; An electrotherapy device.
Experimental: Group 1: High Hertz; Participants will receive 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session. Device: InTENsity MicroCombo	Device: InTENsity MicroCombo; An electrotherapy device.
Sham Comparator: Group 1: Control; Participants will receive 30 hertz stimulation to a non-vagally innervated region of the left ear, delivered in one 15 minute session. Device: InTENsity MicroCombo	Device: InTENsity MicroCombo; An electrotherapy device.
Experimental: Group 2: Pre-stressor; Participants will receive 10 or 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session prior to receiving experimental sympathetic induction. Device: InTENsity MicroCombo	Device: InTENsity MicroCombo; An electrotherapy device.
Experimental: Group 2: Post-stressor; Participants will receive 10 or 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session after experimental sympathetic induction. Device: InTENsity MicroCombo	Device: InTENsity MicroCombo; An electrotherapy device.
Placebo Comparator: Group 2: Control; Participants will receive 10 or 30 hertz stimulation to a non-vagally innervated region of the left ear, delivered in one 15 minute session prior to receiving experimental sympathetic induction. Device: InTENsity MicroCombo	Device: InTENsity MicroCombo; An electrotherapy device.
Experimental: Group 3: 30 Hz; Participants will receive 10 or 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session. Device: InTENsity MicroCombo	Device: InTENsity MicroCombo; An electrotherapy device.
Experimental: Group 4: 30 Hz; Participants will receive 10 or 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session. Participants will also receive stimulation on a subsequent session prior to urodynamic testing. Device: InTENsity MicroCombo	Device: InTENsity MicroCombo; An electrotherapy device.
Experimental: Group 1: Response; Participants will receive 10-30 hertz stimulation to the left auricular branch of the vagus nerve, delivered over the course of 1 hour. Device: InTENsity MicroCombo	Device: InTENsity MicroCombo; An electrotherapy device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in parasympathetic activity after vagal nerve stimulation by Heart Rate Variability	Measured by the normal-to-normal QRS complexes of the PQRST waveform of the electrocardiogram (ECG)	Baseline to 90 minutes post-vagal nerve stimulation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group 1 & 4: Change in acute heart rate response to vagal nerve stimulation	Measured by numerical heart rate in beats per minute	Baseline to 90 minutes post-vagal nerve stimulation
Group 1 & 4: Change in acute blood pressure response to vagal nerve stimulation	Measured by diastolic and systolic blood pressure (mm/Hg)	Baseline to 90 minutes post-vagal nerve stimulation
Group 1: Change in parasympathetic activity after vagal nerve stimulation by Vagus Somatosensory Evoked Potentials	Measured by far field potentials from the brain stem	Baseline to 90 minutes post-vagal nerve stimulation
Group 2 & 4: Change in acute physiological stress response by a change in peripheral cortisol	Measured by cortisol levels in plasma	Baseline to 90 minutes post-experimental stimulus
Group 2 & 4: Change in acute physiological stress response by a change in peripheral catecholamines	Measured by catecholamine levels in plasma	Baseline to 90 minutes post-experimental stimulus
Group 2 & 4: Change in acute physiological stress response by a change in heart rate	Measured by numerical heart rate in beats per minute	Baseline to 90 minutes post-experimental stimulus
Group 2 & 4: Change in acute physiological stress response by a change in blood pressure	Measured by diastolic and systolic blood pressure (mm/Hg)	Baseline to 90 minutes post-experimental stimulus
Group 3 & 4: Change in inflammatory biomarkers after vagal nerve stimulation	Measured by cytokine levels in plasma	Baseline to 90 minutes post-vagal nerve stimulation

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Principal Investigator: Mark S Nash, Ph.D., University of Miami

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2018
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: November 18, 2016
• First Submitted That Met QC Criteria: December 1, 2016
• First Posted (Estimate): December 6, 2016

Study Record Updates

• Last Update Posted (Actual): October 9, 2018
• Last Update Submitted That Met QC Criteria: October 5, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Hyperadrenergia; Inflammatory stress
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries
• Other Study ID Numbers: 20150478

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No