Brain Effect of Vagal Nerve Stimulation at Rest and Pain

NCT04282226 | Withdrawn

• 1 other identifier: QMERC2017/59
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Pain is a ubiquitous distressing sensory experience and is the most frequent symptom in numerous gastrointestinal disorders including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Visceral pain is especially difficult to treat with conventional medications and new treatments are needed. Recently, the relationship between autonomic nerve system (ANS) and pain has gathered attention because it could represent an effective treatment target for visceral pain. The parasympathetic nervous system (PNS), one of the two main branches of the ANS, is considered to play an important role for analgesia possibly due to vagal nerve-mediated activation of key brain areas implicated in descending analgesia of pain. Transcutaneous vagal nerve stimulation (tVNS) can non-invasively modulate vagal nerve and be expected as a new method to treat visceral pain. For example, the preliminary study showed that vagal nerve stimulation experimentally modulated cardiac vagal tone (CVT) and prevented the development of acid-induced oesophageal hyperalgesia. Disturbances in ANS function have been reported not only in IBS patients but also in fibromyalgia and chronic pelvic pain syndrome. Many of these disorders have been associated with differences in brain structure and/or function as demonstrated by the use of structural and functional magnetic resonance imaging (fMRI). Of note, the investigators have recently shown that these differences in brain structure and function may be in part attributable to the aforementioned disturbance in ANS function, adding weight to the proposition that autonomic neuromodulation may be efficacious in pain disorders. For instance, in healthy participants the investigators have recently shown, using functional connectivity analysis, that higher resting parasympathetic CVT predicts the engagement of a subcortical functional network that is implicated in descending analgesia, thereby supporting the notion that vagal-mediated analgesia is achieved via descending inhibitory pathways1,4. Thus, tVNS seems a reasonable method to treat pain. However, to date, the precise real-time effect of tVNS on brain function, including during the processing of visceral pain is unknown. Hence, the aims of this study are to investigate the real-time effect of tVNS compared to sham stimulus on brain activity whilst experiencing acute oesophageal pain, using fMRI in double-blind, randomised crossover study of tVNS vs sham stimulation in healthy subjects.

Conditions

Healthy Volunteer

Keywords

transcutaneous vagal nerve stimulation; functional magnetic resonance imaging; visceral pain; oesophageal stimulation

Outcome Measures

Primary Outcomes (1)

• The effect of tVNS compared to sham stimulus on brain activity whilst experiencing oesophageal pain

  Comparison of fMRI results between sham and active tVNS.

  2 weeks

Secondary Outcomes (6)

• The effect of tVNS on functional brain activity at baseline and following painful oesophageal stimulation

  2 weeks

• The effect of tVNS on participant pain ratings to acute oesophageal pain

  2 weeks

• The effect of baseline autonomic tone on structural brain morphology (both gray and white matter)

  2 weeks

• The effect of tVNS on resting brain function coupled to resting parasympathetic tone, compared to sham stimulus

  2 weeks

• The correlation of structural MR, DTI and resting fMRI data on the efficacy of tVNS for use in visceral pain

  2 weeks

Study Arms (2)

active tVNS

ACTIVE COMPARATOR

The tVNS device will be attached to the left aspect of the neck to stimulate the cervical branch of the vagal nerve and connected to an MR safe electrical

Device: active transcutaneous Vagal Nerve Stimulation (tVNS)

sham tVNS

PLACEBO COMPARATOR

The tVNS device will be attached to anatomically distinct from the cervical branch of the vagal nerve.

Device: sham transcutaneous Vagal Nerve Stimulation (tVNS)

Interventions

active transcutaneous Vagal Nerve Stimulation (tVNS) DEVICE

The tVNS device will be attached to the left aspect of the neck to stimulate the cervical branch of the vagal nerve and connected to an MR safe electrical stimulator.

active tVNS

sham transcutaneous Vagal Nerve Stimulation (tVNS) DEVICE

The tVNS device will be attached to anatomically distinct from the cervical branch of the vagal nerve.

sham tVNS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy participants (defined as those without pre-existing medical comorbidity) from staff, students and the local population of Queen Mary, University of London and/or King's College London
• Women should be studied in the follicular phase of their menstrual cycle or taking oral contraceptives.

You may not qualify if:

• Participants unable to provide informed consent
• Participants with any systemic disease or medications that may influence the autonomic nervous system (e.g. beta-agonists or Parkinson's disease)
• Pregnant or breastfeeding females
• Participants unable to lie flat in the MRI scanner, suffer from claustrophobia or are unsuitable for MRI scanning due to contraindications, comorbidity or in situ metalwork
• Current smokers
• History of anxiety or depression, or hospital anxiety or depression score \>8
• History of drug or alcohol abuse
• Patients who have cardiovascular condition problems
• Patient with cochlear implants
• Recent nasal trauma, base of skull fracture and/or facial surgery that would contraindicate insertion of a nasogastric tube
• A positive urinary drugs screen
• Head circumference exceeding the limits of the scanner

Sponsors & Collaborators

• Queen Mary University of London: lead
• King's College London: collaborator

Study Sites (1)

Queen Mary University of London

London, UK, E1 2AJ, United Kingdom

Location

MeSH Terms

Conditions

Visceral Pain

Condition Hierarchy (Ancestors)

Nociceptive Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Qasim Aziz

  Queen Mary University of London

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and outcomes assessors will be masked.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised, cross-over design with placebo control

Study Record Dates

• First Submitted: February 14, 2020
• First Posted: February 24, 2020
• Study Start: March 16, 2020
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: January 13, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)