Clinical Efficacy of Transcutaneous Auricular Vagal Nerve Stimulation in Irritable Bowel Syndrome and the potential predictive role for the Vagal-Autonomic Neurosignature

The prevalence of irritable bowel syndrome (IBS) in the general population is
5%. IBS affects all age groups across the life span, generally appearing in
late adolescence/early adulthood. Despite the known prevalence and impact of
IBS, its pathophysiology remains unclear. Current consensus, as per the Rome IV
criteria, considers IBS a disorder of the gut-brain interaction, reflecting the
unique bidirectional communication between these two organ systems. In this
study we aim to study the efficacy of a new treatment strategy, namely
transcutaneous auricular vagus nerve stimulation (tVNS). tVNS consisting of
small electrodes that interface with the concha of the outer ear. This area
corresponds to the only place on the surface of the human body where there is
afferent vagal innervation. tVNS is safe, well-tolerated and user-friendly.
Studies have pointed towards beneficial effects of tVNS in depression, epilepsy
and tinnitus, among others, but firmly establishing its therapeutic efficacy
remains warranted. In addition, mechanistic evidence supporting the therapeutic
potential of tVNS is still lacking. Therefore, tVNS is not yet ready for
application in routine clinical practice for any of these conditions. Restoring
the sympathico-vagal disbalance through tVNS can perhaps decrease sensitivity
to pain in IBS. With this study, new results of this potential novel
therapeutic target could fundamentally change the therapeutic landscape of IBS
and other pain disorders.

Primary objective: To study the clinical efficacy of tVNS for the improvement
of abdominal pain in patients with IBS, as measured by the responder rates
based on IBS symptom severity score (IBS-SSS) over an 8-week time period.

Secondary objectives:
To ascertain whether the autonomic-vagal neurosignature, derived from
pre-treatment registration of symptom profiles, autonomic responses and imaging
of neuronal activity as a reaction to stress is able to accurately predict
therapeutic response to tVNS.
To evaluate the effect of treatment on quality of life
To evaluate the effect of treatment on depression
To evaluate the effect of treatment on anxiety
To evaluate the effect of treatment on microbiota composition

This is a single centre, prospective, randomized, double-blind, two-group (1:1)
parallel intervention study for 9 weeks with 6 month follow up.

Group 1 will receive tVNS treatment during 8 weeks, group 2 will be a sham
group with a non-conducting electrode.

This study does not involve any incapacitated or minority groups and is
considered a low-risk study. The patients in the comparator group will continue
with their treatment as usual, without receiving any additional treatment. As
such, this group of patients is not expected to benefit directly from
participation during the treatment period. Patients in the intervention group
are expected to benefit from the treatment in terms of a reduction of IBS
complaints. Serious adverse events have not been reported in studies examining
the efficacy of the tVNS device. Subjects need to visit the university three
times. In the first week they need to complete the ESM and use the Fitbit
during their daily life. During the tVNS treatment, they need to fill in an
electronic questionnaire once a week. Participants will be asked to fill in
electronic questionnaires again after 3 and 6 months after completing the tVNS
treatment.