The Effect of Transcutaneous Vagal Nerve Stimulation on Reducing Oesophageal Pain Hypersensitivity

November 28, 2015 updated by: Adam Farmer, Wingate Institute of Neurogastroenterology

The Effect of Transcutaneous Vagal Nerve Stimulation on Reducing Oesophageal Pain Hypersensitivity in Healthy Volunteers

We are evaluating the role of transcutaneous electrical vagal nerve stimulation in the prevention of oesophageal pain hypersensitivity using a validated human model in healthy volunteers.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Chronic oesophageal pain is a symptomatic feature of disorders such as erosive oesophagitis, non-erosive reflux disease and non-cardiac chest pain. Patients often display heightened sensitivity to intra-oesophageal stimuli, which is referred to as oesophageal pain hypersensitivity. However, the experience of oesophageal pain is highly individual with a multitude of factors proposed to account for this variability. Amongst the physiological factors is the autonomic nervous system (ANS). The ANS has been postulated to play a pivotal role in the modulation of pain through its multiple interactions with pain processing. The ANS has two broadly antithetic branches, the parasympathetic nervous system (PNS) and the sympathetic nervous system (SNS). The primary neural substrate of the PNS is the vagus nerve. The vagus nerve is increasingly considered to play an integral role in modulating oesophageal pain. Electrical vagal nerve stimulation (VNS) was first used in humans in 1988 and is an efficacious treatment for drug resistant epilepsy. Traditional VNS is undertaken in a procedure where a bipolar helical electrode is placed around the cervical vagal nerve, which is connected to a pulse generator placed in subcutaneous pocket in the chest, not dissimilar to a cardiac pacemaker. However, this method of VNS necessitates surgical implantation with its attendant risks and complications. Recently, an external transcutaneous VNS (t-VNS) system, consisting of an earplug-like electrode to interface with the concha of the outer ear and a handheld battery-powered electrical stimulator, has become commercially available (NEMOS system). The auricular branch of the vagus nerve innervates the concha of the ear and is located directly under the skin, making it a suitable target for transcutaneous stimulation. t-VNS has been demonstrated to be safe, well tolerated and have a high degree of user-friendliness. A preliminary study has reported that t-VNS reduces sensitivity to heat pain in healthy volunteers. Furthermore, recent studies have demonstrated that t-VNS patterns of cerebral activation, as determined by functional magnetic resonance imaging, were similar to those evoked by traditional VNS. Thus, VNS per se represents an attractive proposition for investigating the role of the PNS in oesophageal pain and t-VNS specifically, a viable, safe and acceptable technology for achieving this. The pivotal experiments evaluating the analgesic role of VNS in the development of acid induced oesophageal pain hypersensitivity have not been conducted. Using the aforementioned model of oesophageal pain hypersensitivity, we seek to determine the analgesic effect of t-VNS.

Study Type

Interventional

Enrollment (Anticipated)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, E1 @AJ
        • Recruiting
        • Wingate Institute of Neurogastroenterology
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Ability to provide Informed written consent
  • Healthy volunteers aged 18-65, who have no medical history

Exclusion Criteria:

  • Any inclusion criteria not met
  • Subjects unable to provide informed consent.
  • Subjects with any systemic disease or medications that may influence the autonomic nervous system (e.g. beta-agonists or Parkinson's disease).
  • Pregnant females to prevent any confounding effects on pregnancy related nausea.
  • Subjects who suffer from reflux disease
  • Subject who take any medication, including over the counter preparations

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Transcutaneous vagal nerve stimulation
Active vagal nerve stimulation to the left auricular branch of the vagus nerve.
Device: Transcutaneous vagal nerve stimulation
Trans-auricular vagal nerve stimulation
Other Names:
  • NEMOS
Placebo Comparator: Sham vagal nerve stimulation
Placebo vagal nerve stimulation stimulation. The stimulator is attached to the left ear, but rotated 180 degrees, so that it is not stimulating the auricular branch of the vagal nerve.
Device: Transcutaneous vagal nerve stimulation
Trans-auricular vagal nerve stimulation
Other Names:
  • NEMOS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitisation to electrical stimuli in the proximal oesophagus following a distal oesophageal acid infusion in comparison to baseline
Time Frame: 90 minutes post acid infusion
Pain tolerance thresholds to electrical stimulation in the proximal oesophagus decrease following a distal oesophageal acid infusion due to central sensitisation and are defined as a reduction of >6mA in thresholds. Prevention of sensitisation will be defined as this threshold not being met.
90 minutes post acid infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitisation to electrical stimuli in the proximal oesophagus following a distal oesophageal acid infusion in comparison to baseline
Time Frame: 30 minutes post acid infusion
Pain tolerance thresholds to electrical stimulation in the proximal oesophagus decrease following a distal oesophageal acid infusion due to central sensitisation and are defined as a reduction of >6mA in thresholds. Prevention of sensitisation will be defined as this threshold not being met.
30 minutes post acid infusion
Sensitisation to electrical stimuli in the proximal oesophagus following a distal oesophageal acid infusion in comparison to baseline
Time Frame: 60 minutes post acid infusion
Pain tolerance thresholds to electrical stimulation in the proximal oesophagus decrease following a distal oesophageal acid infusion due to central sensitisation and are defined as a reduction of >6mA in thresholds. Prevention of sensitisation will be defined as this threshold not being met.
60 minutes post acid infusion
Effect of vagal nerve stimulation on cardiac vagal tone during stimulation in comparison to baseline
Time Frame: 30 minutes
The effect of vagal stimulation on the validated parameter of cardiac vagal tone
30 minutes
Effect of vagal nerve stimulation on cardiac sympathetic index during stimulation in comparison to baseline
Time Frame: 30 minutes
The effect of vagal stimulation on the validated parameter of cardiac sympathetic index.
30 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wingate Institute of Neurogastroenterology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2014

Primary Completion (Anticipated)

February 1, 2016

Study Completion (Anticipated)

February 1, 2016

Study Registration Dates

First Submitted

December 15, 2014

First Submitted That Met QC Criteria

November 28, 2015

First Posted (Estimate)

December 2, 2015

Study Record Updates

Last Update Posted (Estimate)

December 2, 2015

Last Update Submitted That Met QC Criteria

November 28, 2015

Last Verified

November 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Farmer-2

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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