VIBRANT-IBD: Brain Effects of Non-Invasive Vagus Nerve Stimulation in IBD Remission

Official title

VIBRANT-IBD: Pilot fMRI Study on Neural Correlates of Non-Invasive Vagus Nerve Stimulation in Patients With Inflammatory Bowel Disease in Remission

Overview

The VIBRANT-IBD study is a pilot, prospective, single-arm feasibility study investigating the effects of non-invasive vagus nerve stimulation (nVNS) in adults with inflammatory bowel disease (IBD) in clinical remission. Approximately 15 participants with Crohn's disease or ulcerative colitis will use the Nurosym auricular vagus nerve stimulation device daily for 28 days. Participants will undergo two magnetic resonance imaging (MRI) sessions, one before and one after the intervention. The MRI protocol will include structural imaging, diffusion-weighted imaging, MR angiography, and resting-state functional MRI (rs-fMRI) to assess brain structure and functional connectivity. Before and after the intervention, participants will complete standardised psychological and study-specific questionnaires assessing stress, anxiety, depression, fatigue, emotional functioning, body awareness (interoception), quality of life, gastrointestinal symptom-related experiences, and perceived effects of the intervention. Optional qualitative interviews will additionally explore participants' experiences of living with IBD and using vagus nerve stimulation. The study aims to evaluate the feasibility and preliminary neuropsychological and neurofunctional effects of non-invasive vagus nerve stimulation in individuals with IBD.

Detailed description

The VIBRANT-IBD study is a pilot, prospective, single-arm feasibility study designed to investigate the neuropsychological and neurofunctional effects of non-invasive vagus nerve stimulation (nVNS) in adults with inflammatory bowel disease (IBD) who are in clinical remission.

The study focuses on individuals diagnosed with Crohn's disease or ulcerative colitis and aims to explore the relationship between vagal neuromodulation, brain functional connectivity, emotional functioning, stress regulation, fatigue, and quality of life. Approximately 15 adult participants will be recruited from a gastroenterology outpatient clinic and hospital department.

Participants will undergo a 28-day intervention using the Nurosym device, a non-invasive auricular vagus nerve stimulation system. The stimulation will be self-administered daily following standardised instructions after participant training. The intervention involves stimulation of the auricular branch of the vagus nerve at the tragus area of the ear using mild electrical impulses. Stimulation will deliver at a frequency of 25 Hz with a pulse width of 250 µs. Stimulation intensity will be individually adjusted to a comfortable, clearly perceptible, non-painful level following standardized participant training. The total stimulation time will be 1.5 hours per day. The study aims to evaluate preliminary effects of this intervention, the feasibility, and acceptability in individuals with IBD in remission. Each participant will complete two magnetic resonance imaging sessions: one before the intervention and one after the 28-day stimulation period. MRI examinations will be performed using a 3T Magnetom Vida scanner equipped with a 64-channel head coil. The imaging protocol will include structural and functional neuroimaging assessments. Structural MRI will include standard anatomical imaging, high-resolution three-dimensional T1-weighted magnetisation-prepared rapid acquisition gradient echo (3D MPRAGE), diffusion-weighted imaging (DWI), and non-contrast MR angiography using the time-of-flight (TOF) technique. Functional magnetic resonance imaging (rs-fMRI) will be performed during resting-state conditions using T2-weighted Gradient Echo Echo-Planar Imaging (EPI) sequences to assess functional brain connectivity and neural networks.

Participants will also complete a set of standardised psychological questionnaires before and after the intervention. These measures will assess anxiety (DASS-21), depression (DASS-21), stress (DASS-21), fatigue (IBD-F), resilience (RS14), interoceptive awareness (Brief MAIA-2), and quality of life (WHOQoL BREF). In addition, study-specific questionnaires developed for the project will evaluate, e.g., disease-related concerns, fear of relapse, stress-related gastrointestinal symptoms, and daily functioning. Post-intervention assessments will additionally examine treatment adherence, usability, and acceptability of the stimulation device, perceived therapeutic effects, and potential side effects. Optional qualitative interviews will also be conducted with interested participants to explore personal experiences related to living with IBD and using vagus nerve stimulation therapy.

The primary objective of the study is to explore changes in brain functional connectivity following non-invasive vagus nerve stimulation in adults with IBD in remission. Secondary objectives are to evaluate the feasibility and safety of the intervention and to assess psychological outcomes, including associations between neuroimaging findings and psychological measures.

The study may contribute to a better understanding of brain-gut interactions and the potential role of neuromodulation as a supportive non-pharmacological intervention in IBD.

Interventions

• Device Non-invasive vagus nerve stimulation (nVNS)
  Participants will undergo non-invasive auricular vagus nerve stimulation (nVNS), also referred to as auricular vagal neuromodulation therapy (AVNT). The intervention is neuromodulatory and autonomic in nature and involves transcutaneous electrical stimulation of the auricular branch of the vagus nerve at the tragus region of the ear. The stimulation will be self-administered by participants at home after standardised training provided by the research team. The intervention period will last 28 c

Primary outcome measures

• Change in resting-state functional brain connectivity following non-invasive vagus nerve stimulation [Time frame: Baseline and Day 28 (post-intervention)]
• Change in structural brain imaging measures following non-invasive vagus nerve stimulation [Time frame: Baseline and Day 28 (post-intervention)]

Secondary outcome measures (9)

• Change in anxiety, depression, and stress levels [Time frame: Baseline and Day 28 (post-intervention)]
• Change in fatigue severity [Time frame: Baseline and Day 28 (post-intervention)]
• Change in quality of life [Time frame: Baseline and Day 28 (post-intervention)]
• Change in interoceptive awareness [Time frame: Baseline and Day 28 (post-intervention)]
• Change in psychological resilience [Time frame: Baseline and Day 28 (post-intervention)]
• Change in emotional functioning and stress-related gastrointestinal experiences [Time frame: Baseline and Day 28 (post-intervention)]
• Intervention adherence and usability [Time frame: Day 28 (post-intervention)]
• Occurrence of adverse events [Time frame: Day 28 (post-intervention)]
• Qualitative assessment of participant experiences [Time frame: Up to 1 week after Day 28 intervention completion]

Eligibility criteria

Inclusion criteria

Participants must meet all of the following criteria to be eligible for participation:

• Adults aged 18 years or older.
• Diagnosis of inflammatory bowel disease (IBD), including Crohn's disease or ulcerative colitis.
• Clinical remission of IBD confirmed by medical evaluation.
• Ability to provide informed consent.
• Ability to comply with study procedures and daily use of the stimulation device.
• No contraindications to magnetic resonance imaging (MRI).
• No contraindications to non-invasive vagus nerve stimulation (nVNS).

Exclusion criteria

Participants meeting any of the following criteria will be excluded from the study:

• Active inflammatory bowel disease flare or clinically significant gastrointestinal symptoms.
• Severe or life-threatening comorbid medical conditions (e.g., active cancer).
• Contraindications to MRI, including metallic implants, pacemaker, or severe claustrophobia.
• Contraindications to nVNS, including significant cardiac arrhythmias, severe bradycardia, active implanted electronic medical devices, recent trigeminal neuralgia, or previous vagotomy.
• Current pregnancy.
• Diagnosed with severe neurological or psychiatric disorders.
• Ongoing changes in pharmacological treatment that may affect central nervous system functioning.
• Inability to comply with study procedures or complete study assessments.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Supportive care

Study locations

Poland · 1 center

• Gastroenterology Department / Independent Public Healthcare Centre of the Ministry of Inte — Gdansk

Publications

• Lovibond PF, Lovibond SH. The structure of negative emotional states: comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories. Behav Res Ther. 1995 Mar;33(3):335-43. doi: 10.1016/0005-7967(94)00075-u. PMID 7726811
• Mehling WE, Acree M, Stewart A, Silas J, Jones A. The Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2). PLoS One. 2018 Dec 4;13(12):e0208034. doi: 10.1371/journal.pone.0208034. eCollection 2018. PMID 30513087
• Rogowska AM, Tataruch R, Klimowska K. Validation of the shortened 24-item multidimensional assessment of interoceptive awareness, version 2 (Brief MAIA-2). Sci Rep. 2023 Dec 2;13(1):21270. doi: 10.1038/s41598-023-48536-0. PMID 38042880
• Makara-Studzinska M, Tyburski E, Zaluski M, Adamczyk K, Mesterhazy J, Mesterhazy A. Confirmatory Factor Analysis of Three Versions of the Depression Anxiety Stress Scale (DASS-42, DASS-21, and DASS-12) in Polish Adults. Front Psychiatry. 2022 Jan 4;12:770532. doi: 10.3389/fpsyt.2021.770532. eCollection 2021. PMID 35058818
• Jaracz K, Kalfoss M, Gorna K, Baczyk G. Quality of life in Polish respondents: psychometric properties of the Polish WHOQOL-Bref. Scand J Caring Sci. 2006 Sep;20(3):251-60. doi: 10.1111/j.1471-6712.2006.00401.x. PMID 16922978
• Czuber-Dochan W, Norton C, Bassett P, Berliner S, Bredin F, Darvell M, Forbes A, Gay M, Nathan I, Ream E, Terry H. Development and psychometric testing of inflammatory bowel disease fatigue (IBD-F) patient self-assessment scale. J Crohns Colitis. 2014 Nov;8(11):1398-406. doi: 10.1016/j.crohns.2014.04.013. Epub 2014 May 22. PMID 24856864
• Surzykiewicz J, Konaszewski K, Wagnild G. Polish Version of the Resilience Scale (RS-14): A Validity and Reliability Study in Three Samples. Front Psychol. 2019 Jan 17;9:2762. doi: 10.3389/fpsyg.2018.02762. eCollection 2018. PMID 30705657
• Skrobisz K, Piotrowicz G, Naumczyk P, Sabisz A, Markiet K, Rydzewska G, Szurowska E. Imaging of Morphological Background in Selected Functional and Inflammatory Gastrointestinal Diseases in fMRI. Front Psychiatry. 2020 May 20;11:461. doi: 10.3389/fpsyt.2020.00461. eCollection 2020. PMID 32508692

Identifiers

NCT: NCT07636304 · KB 17/26 · 2025/09/X/HS6/01840 · 2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗