Periodic Reporting for period 1 - RESILIENCE (Rediscovering the Wanderer: restoration of sympathico-vagal disbalance in irritable bowel syndrome by neuromodulation – a novel therapeutic concept)
Okres sprawozdawczy: 2023-05-01 do 2025-10-31
Common colloquial phrases like ‘gut feeling’ or ‘butterflies in my belly’ are not just idioms but reflect on the unique communication between gut and brain. The principal interface for this interaction is the autonomic nervous system — a largely subconscious system that manages bodily functions through a delicate balance between its two branches: the sympathetic and parasympathetic nervous systems. The vagus nerve is the main component of the latter. Diminished vagal tone resulting in increased sensitivity to pain is characteristic for many chronic pain disorders, including irritable bowel syndrome (IBS). People with IBS have frequent and often severe abdominal pain. While its etiology remains poorly understood, IBS is now assumed to be caused by a malfunctioning of the gut–brain axis, often manifesting in sympathetico–vagal disbalance. However, no established therapies currently target this neurological disturbance. I hypothesize that restoring the sympathico–vagal disbalance through autonomic neuromodulation can be an important novel therapeutic target in IBS. To achieve this, I will use transcutaneous electrical vagus nerve stimulation via the auricular nerve. I will also develop a novel multimodal ‘vagal-autonomic neurosignature’ through combining actively and passively recorded biometrics and high-power field neuroimaging. This profile will allow identification of patients who could benefit from the new treatment approach. Simultaneously, I will investigate mechanisms of action in a comprehensive manner, using experimental models and tools I have previously developed. My project is foreseen to fundamentally change the therapeutic landscape of IBS and other pain disorders by providing high-quality clinical and mechanistic evidence for the efficacy of vagal neuromodulation. Identifying a neurological signature of patients that likely benefit from this approach would represent a major break-through in individualizing therapeutic efforts in IBS.
The entire project is organised into 4 scientific packages (WPs). The WPs address 4 separate clinical studies concerning studies in patients with irritable bowel syndrome (IBS, WP1) and healthy volunteers (WP2-4).
For all 4 human intervention studies, all necessary ethical and legal clearance has been obtained. The (digital) infrastructure needed for the execution is in place. We have purchased the necessary equipment, in particular the devices needed to deliver the transcutaneous auricular vagus nerve stimulation. Two PhD students and a postdoc have been recruited for this project. A senior statistician will join the research team in a later stage of the project.
The progress of the different work packages is as follows (as per 1st May 2025):
WP1: This WP involves the execution of a large clinical study including IBS patients. Inclusion of 166 patients is foreseen, who first undergo extensive phenotyping including functional magnetic resonance imaging at 7 Tesla and recording of autonomic parameters using wearables, whereafter they are randomised to undergo transcutaneous auricular vagus nerve stimulation (tVNS) or sham for a period of 8 weeks. 73 of 166 patients have been included. Of these individuals, 51 patients have completed the 8-week treatment period and 22 have also completed the 6-month follow-up period.
WP2: This WP involves studying pain perception and signal processing in healthy volunteers using the intraduodenal infusion of capsaicin and 7T fMRI neuroimaging. All subjects included and test days completed, analyses of data ongoing.
WP3: This WP investigates gastrointestinal motor responses to tVNS in healthy volunteers. Of the 13 participants, 6 have been included. The first test day is to commence on the 15th of July 2025.
WP4: This WP addresses the effect of vagus nerve stimulation on the acute stress respons. 24 participants have been included of the total of 60 (40%), of whom 6 have completed the test day.
Progress update as of 31st October 2025:
WP1: 109 patients included of whom 82 patients have finished the treatment period.
WP2: Preliminary data analysis has been performed. An abstract has been submitted to the 2026 Annual meeting of the International Society for Magnetic Resonance in Medicine.
WP3: 7 participants have been included, 6 test days have been completed.
WP4: 43 participants have been included of whom 37 have completed the test day.
For all 4 human intervention studies, all necessary ethical and legal clearance has been obtained. The (digital) infrastructure needed for the execution is in place. We have purchased the necessary equipment, in particular the devices needed to deliver the transcutaneous auricular vagus nerve stimulation. Two PhD students and a postdoc have been recruited for this project. A senior statistician will join the research team in a later stage of the project.
The progress of the different work packages is as follows (as per 1st May 2025):
WP1: This WP involves the execution of a large clinical study including IBS patients. Inclusion of 166 patients is foreseen, who first undergo extensive phenotyping including functional magnetic resonance imaging at 7 Tesla and recording of autonomic parameters using wearables, whereafter they are randomised to undergo transcutaneous auricular vagus nerve stimulation (tVNS) or sham for a period of 8 weeks. 73 of 166 patients have been included. Of these individuals, 51 patients have completed the 8-week treatment period and 22 have also completed the 6-month follow-up period.
WP2: This WP involves studying pain perception and signal processing in healthy volunteers using the intraduodenal infusion of capsaicin and 7T fMRI neuroimaging. All subjects included and test days completed, analyses of data ongoing.
WP3: This WP investigates gastrointestinal motor responses to tVNS in healthy volunteers. Of the 13 participants, 6 have been included. The first test day is to commence on the 15th of July 2025.
WP4: This WP addresses the effect of vagus nerve stimulation on the acute stress respons. 24 participants have been included of the total of 60 (40%), of whom 6 have completed the test day.
Progress update as of 31st October 2025:
WP1: 109 patients included of whom 82 patients have finished the treatment period.
WP2: Preliminary data analysis has been performed. An abstract has been submitted to the 2026 Annual meeting of the International Society for Magnetic Resonance in Medicine.
WP3: 7 participants have been included, 6 test days have been completed.
WP4: 43 participants have been included of whom 37 have completed the test day.
The project so far has produced an overview article and a systematic review article, in addition to a popular article and an invited lecture. Preliminary results have been presented at the Digestive Disease Week conference in 2025.
Given we are still in the beginning of the project awaiting the main results, we do not consider the current (preliminary) findings of moving significantly beyond the state-of-the-art. We anticipate achieving this once more results become available. The current results are in line with what we had anticipated.
We hope that the final results will be instrumental to revolutionising the treatment for irritable bowel syndrome and understanding potential mechanisms of action. In addition, it will generate the largest sample of neuroimaging data in IBS using high-power field MRI.
Given we are still in the beginning of the project awaiting the main results, we do not consider the current (preliminary) findings of moving significantly beyond the state-of-the-art. We anticipate achieving this once more results become available. The current results are in line with what we had anticipated.
We hope that the final results will be instrumental to revolutionising the treatment for irritable bowel syndrome and understanding potential mechanisms of action. In addition, it will generate the largest sample of neuroimaging data in IBS using high-power field MRI.