Clinical trial NCT04296552: Brain-Gut-Microbiota Interaction in IBS
Official title: Study Protocol of the Bergen Brain-gut-microbiota-axis Study: a Prospective Case-report Characterization and Dietary Intervention Study to Evaluate the Effects of Microbiota Alterations on Cognition and Anatomical and Functional Brain Connectivity in Patients With Irritable Bowel Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Irritable Bowel Syndrome
Functional Gastrointestinal Disorders
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
Collaborators: name: National Research Council, Spain
name: Genetic Analysis AS
name: Lovisenberg Diakonale Hospital
name: University of Bergen
First posted: 2020-03-05
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study is an open, single-centre, case-control characterisation study, followed by open label dietary intervention for a subgroup of subjects with IBS-D. Exploratory trial.
Primary purpose: TREATMENT

Brief summary: Are you what you eat? How can dietary components influence microbial composition of the gut and function of the peripheral and central nervous system? The gut and brain is linked through complex mechanisms of sensorimotor functions of the immune system, the hypothalamic-pituitary-adrenal-axis, the enteric nervous system and microbiota.

In this project, a multitude of factors contributing to the bidirectional neurobiological communication along the brain-but-axis will be investigated. No disease of the brain-gut axis has been elucidated, therefore our investigations involves approaching a large span of components and processes involved in the axis. This study is carried out as a case-report study (baseline, IBS n=100, healthy controls n=40) followed by a dietary intervention (IBS-D n=60). Through multivariate analyses, the investigators will identify patterns of factors contributing to patient symptomatology and pathology, followed by big data analysis leading to stratification of sub-classification of irritable bowel syndrome (IBS).

Detailed description: Data from deep phenotype characterization of 100 patients with IBS and 40 healthy age (between 18 and 65) and gender-matched controls will be collected between May 2019 and December 2021. Psychometric tests, questionnaires, biological samples (blood, faeces, saliva and GI biopsies from antrum, duodenum and sigmoid colon), assessment of gastric accommodation and emptying using transabdominal ultrasound, vagal activity, and functional and structural magnetic resonance imaging (MRI) of the brain, will be carried out. A subgroup of 60 patients with IBS-D will be further included in a 12-week low Fermentable Oligo-, Di-, Mono-saccharides And Polyols (FODMAP) dietary intervention-study to determine short and long-term effects of diet on symptoms, microbiota composition, molecular GI signatures, cognition and behavioural traits, and structural and functional brain signatures. Deep machine learning, prediction tools and big data analysis will be used for multivariate analysis allowing disease stratification and diagnostic biomarker detection.

Eligibility criteria: Inclusion Criteria:

* Subject must be between 18 and 65 years of age
* Fulfil the ROME-IV criteria for IBS

  1. Had recurrent abdominal pain on average at least 1 day per week during the previous 3 months that is associated with alterations in bowel habits.
  2. Duration at least six months.

Exclusion Criteria:

* Pharmacological treatment affecting the GI-tract, including treatment for depression
* Organic disease:

  1. coeliac disease
  2. inflammatory bowel disease
  3. neurological diseases
  4. diabetes
  5. active helicobacter pylori infection
  6. polycystic ovary syndrome
* Treated with systemic antibiotics within the last 3 months
* Use painkillers regularly, other than paracetamol
* Pregnant
* Previous intestinal surgery (appendectomy is OK)
* Claustrophobic or have metallic implants that are not MR compatible
* Vegan or vegetarian
* Been travelling outside Europe within the last three weeks (or plan to travel in the nearest future)
* Probiotics or lowFODMAP-diet within the last three weeks
* Participation in any other simultaneous clinical study
* Inability to comprehend and respond to questionnaires or follow dietary guidance

Primary outcomes:
measure: Short-term dietary lowFODMAP responder will be measured using IBS-symptom severity score
timeFrame: At 4 weeks
measure: Long-term dietary lowFODMAP responder will be measured using the IBS-symptom severity score
timeFrame: At 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland University Hospital
state: Vestlandet
Study officials:
References:
citation: Berentsen B, Nagaraja BH, Teige EP, Lied GA, Lundervold AJ, Lundervold K, Steinsvik EK, Hillestad ER, Valeur J, Bronstad I, Gilja OH, Osnes B, Hatlebakk JG, Haasz J, Labus J, Gupta A, Mayer EA, Benitez-Paez A, Sanz Y, Lundervold A, Hausken T. Study protocol of the Bergen brain-gut-microbiota-axis study: A prospective case-report characterization and dietary intervention study to evaluate the effects of microbiota alterations on cognition and anatomical and functional brain connectivity in patients with irritable bowel syndrome. Medicine (Baltimore). 2020 Sep 11;99(37):e21950. doi: 10.1097/MD.0000000000021950.