Esophageal DiseasesNCT02620176
The Effect of Transcutaneous Vagal Nerve Stimulation on Reducing Oesophageal Pain Hypersensitivity
A study testing Transcutaneous vagal nerve stimulation in people with Esophageal Diseases, run by Wingate Institute of Neurogastroenterology at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Esophageal Diseases
- What is being tested?
- Transcutaneous vagal nerve stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2014to Feb 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Ability to provide Informed written consent
- Healthy volunteers aged 18-65, who have no medical history
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Wingate Institute of Neurogastroenterology
London, London, E1 @AJ
ADam Farmer, PhD MRCP, +442078822640, a.farmer@qmul.ac.uk
Susan Surguy, PhD, +442078822645, s.surguy@qmul.ac.uk
About this study
Official title: 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.
Read the 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.
- Conditions
- Esophageal Diseases
- Being tested
- Transcutaneous vagal nerve stimulation
- Medical subject headings
- Esophageal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous vagal nerve stimulationDevice
Also called NEMOS
Trans-auricular vagal nerve stimulation
| Study group | Role | What they receive |
|---|---|---|
| Transcutaneous vagal nerve stimulation | Experimental | Active vagal nerve stimulation to the left auricular branch of the vagus nerve. Receives: Device: Transcutaneous vagal nerve stimulation |
| Sham vagal nerve stimulation | Placebo comparator | 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. Receives: Device: Transcutaneous vagal nerve stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitisation to electrical stimuli in the proximal oesophagus following a distal oesophageal acid infusion in comparison to baseline
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.
Measured: 90 minutes post acid infusion
Secondary outcomes (4)
Sensitisation to electrical stimuli in the proximal oesophagus following a distal oesophageal acid infusion in comparison to baseline
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.
Measured: 30 minutes post acid infusion
Sensitisation to electrical stimuli in the proximal oesophagus following a distal oesophageal acid infusion in comparison to baseline
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.
Measured: 60 minutes post acid infusion
Effect of vagal nerve stimulation on cardiac vagal tone during stimulation in comparison to baseline
The effect of vagal stimulation on the validated parameter of cardiac vagal tone
Measured: 30 minutes
Effect of vagal nerve stimulation on cardiac sympathetic index during stimulation in comparison to baseline
The effect of vagal stimulation on the validated parameter of cardiac sympathetic index.
Measured: 30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2015 (estimated)
- Study startDec 2014
- Primary completionFeb 2016 (estimated)
- Study completionFeb 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Esophageal DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wingate Institute of Neurogastroenterology
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Adam Farmer, Wingate Institute of Neurogastroenterology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02620176
- Sponsor's protocol ID
- Farmer-2
- Status last verified
- Nov 2015
- First submitted
- 15 Dec 2014
- Last updated
- 2 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Botha C, Farmer AD, Nilsson M, Brock C, Gavrila AD, Drewes AM, Knowles CH, Aziz Q. Preliminary report: modulation of parasympathetic nervous system tone influences oesophageal pain hypersensitivity. Gut. 2015 Apr;64(4):611-7. doi: 10.1136/gutjnl-2013-306698. Epub 2014 May 28.
PubMed 24870622
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Transcutaneous Vagal Nerve Stimulation on Reducing Oesophageal Pain Hypersensitivity in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02620176
- Acronym / sponsor ID
- Farmer-2
- Conditions
- Esophageal Diseases
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Wingate Institute of NeurogastroenterologyUniversity, hospital or other
- Study start
- Dec 2014
- Primary completion
- Feb 2016 (estimated)
- Study completion
- Feb 2016 (estimated)
- First posted
- 2 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transcutaneous vagal nerve stimulation | Experimental | Device: Transcutaneous vagal nerve stimulationActive vagal nerve stimulation to the left auricular branch of the vagus nerve. |
| Sham vagal nerve stimulation | Placebo comparator | Device: Transcutaneous vagal nerve stimulationPlacebo 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Ability to provide Informed written consent
- Healthy volunteers aged 18-65, who have no medical history
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcutaneous vagal nerve stimulationAlso: NEMOSTrans-auricular vagal nerve stimulation | Device | Sham vagal nerve stimulation, Transcutaneous vagal nerve stimulation |
Primary outcome
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.
4 secondary outcomes
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
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
Effect of vagal nerve stimulation on cardiac vagal tone during stimulation in comparison to baseline
Time frame: 30 minutes
Effect of vagal nerve stimulation on cardiac sympathetic index during stimulation in comparison to baseline
Time frame: 30 minutes
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2015.
- Background: PubMed 24870622Botha C, Farmer AD, Nilsson M, Brock C, Gavrila AD, Drewes AM, Knowles CH, Aziz Q. Preliminary report: modulation of parasympathetic nervous system tone influences oesophageal pain hypersensitivity. Gut. 2015 Apr;64(4):611-7. doi: 10.1136/gutjnl-2013-306698. Epub 2014 May 28.
- Description: Vagal nerve stimulator informationLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous vagal nerve stimulation in people with Esophageal Diseases, run by Wingate Institute of Neurogastroenterology at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Adam D Farmer, PhD MRCP (02088822640, a.farmer@qmul.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02620176, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2015.