Brain-Gut-Microbiota Interaction in IBS

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

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).

Study Overview

• Status: Recruiting
• Conditions: Irritable Bowel Syndrome; Functional Gastrointestinal Disorders
• Intervention / Treatment: Other: Dietary lowFODMAP intervention

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.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Birgitte Berentsen, PhD; Phone Number: +4791545159; Email: birgitte.berentsen1@helse-bergen.no
• Study Contact Backup: Name: Gülen A Lied, MD., PhD; Phone Number: +4793411359; Email: gulen.arslan.lied@helse-bergen.no

Study Locations

• Norway
  • Vestlandet
    • Bergen, Vestlandet, Norway, 5021
      • Recruiting
      • Haukeland University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 12 week lowFODMAP dietary intervention; Patients with IBS-D are enrolled in a 12 week strict lowFODMAP dietary intervention study.	Other: Dietary lowFODMAP intervention; Twelve week strict lowFODMAP dietary intervention, involving restricted intake of fermentable carbohydrates (FODMAPs).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short-term dietary lowFODMAP responder will be measured using IBS-symptom severity score	A minimum of 50 point reduction in IBS-symptom severity score (range 0-500: mild (75-175), moderate (175-300) and severe (>300), below 75 (remission))	At 4 weeks
Long-term dietary lowFODMAP responder will be measured using the IBS-symptom severity score	A minimum 50 point reduction in IBS-symptom severity score (range 0-500: mild (75-175), moderate (175-300) and severe (>300), below 75 (remission))	At 12 weeks

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Collaborators: University of Bergen; National Research Council, Spain; Lovisenberg Diakonale Hospital; Genetic Analysis AS

Publications and helpful links

General Publications

• 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.

Helpful Links

• Website for project description, participant information and contact details.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2019
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: March 4, 2020
• First Submitted That Met QC Criteria: March 4, 2020
• First Posted (Actual): March 5, 2020

Study Record Updates

• Last Update Posted (Actual): June 30, 2020
• Last Update Submitted That Met QC Criteria: June 28, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Gastrointestinal Diseases; Digestive System Diseases
• Other Study ID Numbers: 2015-01621

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified stool samples, blood chemistry and symptom severity scores will be shared with collaborators.
• IPD Sharing Time Frame: The data will become available post microbiota-analysis until the end of the study period.
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

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