Vagal Nerve Stimulation in Irritable Bowel Syndrome (RESILIENCE)

Clinical Efficacy of Transcutaneous Auricular Vagal Nerve Stimulation in Irritable Bowel Syndrome and the Potential Predictive Role for the Vagal-Autonomic Neurosignature

This randomized control trial aims to evaluate the effect of transcutaneous auricular vagal nerve stimulation in patients with irritable bowel syndrome. The intervention will be 8 weeks of treatment with a vagal nerve stimulator. The main objectives are:

• To evaluate the clinical response, defined as a decrease of at least 50 points on the IBS-SSS questionnaire, of the treatment.
• 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 predict therapeutic response to tVNS accurately.
• 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 Participants will be asked to wear a wearable (Fitbit) and fill out a daily questionnaire for one week. Thereafter, a functional brain MRI will be performed.

In the intervention group patients will receive transcutaneous nerve stimulation for 8-weeks at home. The comparison group will receive the same device but with a non-conducting electrode.

Patients fill out weekly questionnaires during the treatment period and at follow-up moments 3 and 6 months after finishing the treatment period.

Study Overview

• Status: Recruiting
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Device: Vagal Nerve Stimulation; Device: Sham stimulation

• Study Type: Interventional
• Enrollment (Estimated): 166
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kimberly Hawinkels; Phone Number: 0883887808; Email: kimberly.hawinkels@maastrichtuniversity.nl

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229ER
      • Recruiting
      • Maastricht University
      • Contact: Kimberly Hawinkels; Email: kimberly.hawinkels@maastrichtuniversity.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A diagnosis of IBS according to Rome IV criteria (3), as follows:
• Recurrent abdominal pain, on average, at least 1 day per week in the last 3 months, associated with 2 or more of the following criteria:
• Related to defecation.
• Associated with a change in stool frequency.
• Associated with a change in stool from (appearance).
• Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis.
• Age between 18 and 75 years;
• Ability to understand and speak the Dutch language.
• Ability to understand how to utilize the ESM application.

Exclusion Criteria:

• A history of abdominal surgery, except for uncomplicated appendectomy, laparoscopic cholecystectomy and hysterectomy is present or otherwise based on the principal investigator's judgement.
• Presence of metallic prostheses, pacemakers, metal clips on blood vessels, metal parts in the eye, an intrauterine device (with the exception of the Mirena IUD), metal braces, facial tattoos and/or metal objects.
• History of major head trauma or head/brain surgery
• History of claustrophobia
• Pregnancy, lactation, intention to become pregnant during the study period
• Students and employees of Maastricht University are not precluded from participation, unless they have a direct personal, professional or hierarchical position with regards to any of the study team members or their department.
• If the subject has a cardiac arrhythmia, the attending physician will be consulted before participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention; transcutaneous auricular vagal nerve stimulation, for 8 weeks at least one hour a day	Device: Vagal Nerve Stimulation; Transcutaneous Auricular Vagal Nerve Stimulation
Placebo Comparator: placebo; sham stimulation with a non-conducting electrode, for 8 weeks at least one hour a day	Device: Sham stimulation; Sham stimulation with a non-conduction electrode

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical meaningful decrease in severity of GI-symptoms	Measuring IBS-SSS, defined as a decrease of at least 50 points	at the end of the 8 week treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive value of neuro-signature	The value of the multimodal neuro-signature in the prediction of clinical response to tVNS in IBS-patients.	at the end of the 8 week treatment period
adverse events	Number and severity of adverse events	at the end of the 8 week treatment period
Anxiety/depression	Symptoms of anxiety and depression measured using PHQ-9 and GAD-7	at the end of the 8 week treatment period
Cost-effectiveness	Direct and indirect costs made during the treatment period	at follow up moment 2 (6 months after 8 week treatment period)
Time the device was used	The amount of time patients used the tVNS device	at the end of the 8 week treatment period

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Daniel Keszthelyi, Maastricht University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: October 3, 2023
• First Submitted That Met QC Criteria: October 16, 2023
• First Posted (Actual): October 19, 2023

Study Record Updates

• Last Update Posted (Actual): August 2, 2024
• Last Update Submitted That Met QC Criteria: August 1, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: vagal nerve stimulation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome
• Other Study ID Numbers: NL84720.068.23

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No