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Vagal Nerve Stimulation to Reduce Inflammation and Hyperadrenergia

Primary Purpose

Spinal Cord Injury

Status

Withdrawn

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

InTENsity MicroCombo

About this trial

This is an interventional basic science trial for Spinal Cord Injury focused on measuring Hyperadrenergia, Inflammatory stress

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Group 1 & 2:

Inclusion Criteria:

Age 18-65
Willingness to participate in the study

Exclusion Criteria:

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

Group 3:

Inclusion Criteria:

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

Exclusion Criteria:

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

Group 4:

Inclusion Criteria:

Age 18-65
≥ 1-year post-injury
Bladder management by clean intermittent catheterization
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.
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.
Willingness to participate in the study.

Exclusion Criteria:

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

Sites / Locations

The Miami Project to Cure Paralysis/ University of Miami

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Sham Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

Group 1: Low Hertz

Group 1: High Hertz

Group 1: Control

Group 2: Pre-stressor

Group 2: Post-stressor

Group 2: Control

Group 3: 30 Hz

Group 4: 30 Hz

Group 1: Response

Arm Description

Participants will receive 10 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session. Device: InTENsity MicroCombo

Participants will receive 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session. Device: InTENsity MicroCombo

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

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Group 1 & 4: Change in acute heart rate response to vagal nerve stimulation

Measured by numerical heart rate in beats per minute

Group 1 & 4: Change in acute blood pressure response to vagal nerve stimulation

Measured by diastolic and systolic blood pressure (mm/Hg)

Group 1: Change in parasympathetic activity after vagal nerve stimulation by Vagus Somatosensory Evoked Potentials

Measured by far field potentials from the brain stem

Group 2 & 4: Change in acute physiological stress response by a change in peripheral cortisol

Measured by cortisol levels in plasma

Group 2 & 4: Change in acute physiological stress response by a change in peripheral catecholamines

Measured by catecholamine levels in plasma

Group 2 & 4: Change in acute physiological stress response by a change in heart rate

Measured by numerical heart rate in beats per minute

Group 2 & 4: Change in acute physiological stress response by a change in blood pressure

Measured by diastolic and systolic blood pressure (mm/Hg)

Group 3 & 4: Change in inflammatory biomarkers after vagal nerve stimulation

Measured by cytokine levels in plasma

Full Information

NCT ID

NCT02983266

First Posted

November 18, 2016

Last Updated

October 5, 2018

Sponsor

University of Miami

1. Study Identification

Unique Protocol Identification Number

NCT02983266

Brief Title

Vagal Nerve Stimulation to Reduce Inflammation and Hyperadrenergia

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Withdrawn

Why Stopped

Insufficient funding

Study Start Date

December 1, 2018 (Anticipated)

Primary Completion Date

December 1, 2020 (Anticipated)

Study Completion Date

December 1, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Miami

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

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

Spinal Cord Injury

Keywords

Hyperadrenergia, Inflammatory stress

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1: Low Hertz

Arm Type

Experimental

Arm Description

Participants will receive 10 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session. Device: InTENsity MicroCombo

Arm Title

Group 1: High Hertz

Arm Type

Experimental

Arm Description

Participants will receive 30 hertz stimulation to the left auricular branch of the vagus nerve, delivered in one 15 minute session. Device: InTENsity MicroCombo

Arm Title

Group 1: Control

Arm Type

Sham Comparator

Arm Description

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

Arm Title

Group 2: Pre-stressor

Arm Type

Experimental

Arm Description

Arm Title

Group 2: Post-stressor

Arm Type

Experimental

Arm Description

Arm Title

Group 2: Control

Arm Type

Placebo Comparator

Arm Description

Arm Title

Group 3: 30 Hz

Arm Type

Experimental

Arm Description

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

Arm Title

Group 4: 30 Hz

Arm Type

Experimental

Arm Description

Arm Title

Group 1: Response

Arm Type

Experimental

Arm Description

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

Intervention Type

Device

Intervention Name(s)

InTENsity MicroCombo

Intervention Description

An electrotherapy device.

Primary Outcome Measure Information:

Title

Change in parasympathetic activity after vagal nerve stimulation by Heart Rate Variability

Description

Measured by the normal-to-normal QRS complexes of the PQRST waveform of the electrocardiogram (ECG)

Time Frame

Baseline to 90 minutes post-vagal nerve stimulation

Secondary Outcome Measure Information:

Title

Group 1 & 4: Change in acute heart rate response to vagal nerve stimulation

Description

Measured by numerical heart rate in beats per minute

Time Frame

Baseline to 90 minutes post-vagal nerve stimulation

Title

Group 1 & 4: Change in acute blood pressure response to vagal nerve stimulation

Description

Measured by diastolic and systolic blood pressure (mm/Hg)

Time Frame

Baseline to 90 minutes post-vagal nerve stimulation

Title

Group 1: Change in parasympathetic activity after vagal nerve stimulation by Vagus Somatosensory Evoked Potentials

Description

Measured by far field potentials from the brain stem

Time Frame

Baseline to 90 minutes post-vagal nerve stimulation

Title

Group 2 & 4: Change in acute physiological stress response by a change in peripheral cortisol

Description

Measured by cortisol levels in plasma

Time Frame

Baseline to 90 minutes post-experimental stimulus

Title

Group 2 & 4: Change in acute physiological stress response by a change in peripheral catecholamines

Description

Measured by catecholamine levels in plasma

Time Frame

Baseline to 90 minutes post-experimental stimulus

Title

Group 2 & 4: Change in acute physiological stress response by a change in heart rate

Description

Measured by numerical heart rate in beats per minute

Time Frame

Baseline to 90 minutes post-experimental stimulus

Title

Group 2 & 4: Change in acute physiological stress response by a change in blood pressure

Description

Measured by diastolic and systolic blood pressure (mm/Hg)

Time Frame

Baseline to 90 minutes post-experimental stimulus

Title

Group 3 & 4: Change in inflammatory biomarkers after vagal nerve stimulation

Description

Measured by cytokine levels in plasma

Time Frame

Baseline to 90 minutes post-vagal nerve stimulation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Group 1 & 2: Inclusion Criteria: Age 18-65 Willingness to participate in the study Exclusion Criteria: Use of an active electrical implant, such as a cardiac pacemaker or cochlear implant Use of a hearing aid in the left ear Use of an implanted insulin or morphine (pain) pump Self-reported history of syncope from known or unknown origins Self-reported history of cardiovascular disease or dysfunction (e.g., cardiovascular disease, arrhythmia, congestive heart failure, or stroke) Group 3: Inclusion Criteria: Age 18-65 Overweight, with a BMI ≥ 27 Presence of chronic inflammation, with C-reactive protein values > 3 mg/l Willingness to participate in the study Exclusion Criteria: Use of an active electrical implant, such as a cardiac pacemaker or cochlear implant Use of a hearing aid in the left ear Use of an implanted insulin or morphine (pain) pump Self-reported history of syncope from known or unknown origins Self-reported history of cardiovascular disease or dysfunction (e.g., cardiovascular disease, arrhythmia, congestive heart failure, or stroke) Use of statin drugs Group 4: Inclusion Criteria: Age 18-65 ≥ 1-year post-injury Bladder management by clean intermittent catheterization 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. 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. Willingness to participate in the study. Exclusion Criteria: Currently hospitalized American Spinal Injury Association (AIS) C-E Currently using an insulin, morphine (pain), or intrathecal pump Use of an active electrical implant, such as a cardiac pacemaker or cochlear implant Use of a hearing aid in the left ear Self-reported history of syncope from known or unknown origins Self-reported history of cardiovascular disease or dysfunction (e.g., cardiovascular disease, arrhythmia, congestive heart failure, or stroke)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark S Nash, Ph.D.

Organizational Affiliation

University of Miami

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Miami Project to Cure Paralysis/ University of Miami

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Vagal Nerve Stimulation to Reduce Inflammation and Hyperadrenergia

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