Vagal Nerve Stimulation in Irritable Bowel Syndrome

Study Overview
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Brief Summary
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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.

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

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Device: Vagal Nerve Stimulation
* Device: Sham stimulation


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vagal nerve stimulation