Using a Transcutaneous Electrical Auricular Stimulator to Harness the Cholinergic Anti-Inflammatory Pathway (TEACAP)

Persistent chronic inflammation is an important underlying event in multiple diseases including rheumatoid arthritis, inflammatory bowel diseases and type 2 diabetes. These disorders are characterized as inflammatory in part because of the important mediating role of pro-inflammatory cytokines in their pathogenesis. This study will investigate whether transcutaneous auricular electrical stimulation of the vagus nerve will affect and decrease the inflammatory cytokine response in healthy individuals.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Device: Vagus Nerve Stimulation; Device: Sham Vagus Nerve Stimulation

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Manhasset, New York, United States, 11030
      • Feinstein Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age between 18-60 years,
2. Currently healthy with no medical problems
3. Able and willing to give written informed consent and comply with the requirements of the study protocol.

Exclusion Criteria:

1. History of any of the following: cardiac arrhythmia, coronary artery disease, autoimmune disease, chronic inflammatory disease, anemia, malignancy, depression, neurologic disease, diabetes mellitus, renal disease, malignancy, dementia, psychiatric illness including active psychosis, or any other chronic medical condition.
2. Family history of inflammatory disease
3. Treatment with an anti-cholinergic medication, including over the counter medications,
4. Implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators.
5. Current tobacco or nicotine user (to limit potential confounding effects of exposure to nicotine),
6. Chronic inflammatory disorders
7. Investigational drug and/or treatment during the 28 days or seven half-lives of the investigational drug prior to the start of study drug dosing (Day 0), whichever is the greater length of time,
8. Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to a study intervention,
9. Pregnancy or lactation (Pregnancy status & lactation will be determined via self-report),
10. Implanted vagus nerve stimulator
11. Inability to comply with study procedures
12. Ear infection (otitis media or externa)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vagus Nerve Stimulation; Device: Vagus nerve stimulation Patients will receive transcutaneous stimulation of the auricular branch of the left vagus nerve for 5 minutes.	Device: Vagus Nerve Stimulation; Patients will receive transcutaneous stimulation of the auricular branch of the left vagus nerve for 5 minutes. Blood will be withdrawn prior to stimulation and 1 hour following the stimulation. The device is a handheld electrical pulse generator and a pair of electrodes to be placed at the ear for stimulation. The specific target at the ear will be the auricular branch of the vagus nerve which innervates the skin of the ear canal. Electrodes will be placed near/at the entrance to the canal of the ear to provide stimulation to the auricular branch of the vagus nerve.
Sham Comparator: Sham Vagus Nerve Stimulation; Patients will receive sham transcutaneous stimulation of the auricular branch of the left vagus nerve for 5 minutes.	Device: Sham Vagus Nerve Stimulation; Patients will receive sham transcutaneous stimulation of the auricular branch of the left vagus nerve for 5 minutes. Blood will be withdrawn prior to stimulation and 1 hour following the stimulation. Sham stimulation will be performed in the identical manner as true transcutaneous stimulation except that the patient will not receive electrical stimulation of the vagus nerve.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipopolysaccharide stimulated levels of TNF in whole blood.	Whole blood will be taken from patients and stimulated by lipopolysaccharide. Levels of TNF produced by the cells in the whole blood after 4 hours of incubation will be measured.	4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipopolysaccharide stimulated levels of cytokines such as IL-1, IL-6, IL-8, IL-10 and HMGB1 in whole blood.	Whole blood will be taken from patients and stimulated by lipopolysaccharide. Levels of cytokines such as IL-1, IL-6, IL-8, IL-10 and HMGB1 that are produced by the cells in the whole blood after 4 hours of incubation will be measured.	4 hours
Percentage of subjects with treatment emergent adverse events	The percentage of participants with treatment emergent adverse events will be assessed using the NCI-CTAEversion4.	1 hour

Collaborators and Investigators

• Sponsor: Northwell Health
• Investigators: Principal Investigator: Cynthia Aranow, MD, Northwell Health

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): December 13, 2023
• Study Completion (Actual): December 13, 2023

Study Registration Dates

• First Submitted: September 20, 2016
• First Submitted That Met QC Criteria: September 20, 2016
• First Posted (Estimated): September 22, 2016

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation, Vagus Nerve Stimulation
• Other Study ID Numbers: HS16-0530

Plan for Individual participant data (IPD)

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