Modulation of Intestinal Barrier Function and Inflammation Via Butyrate-promoting Dietary Fibre

Not Applicable

• Conditions: Microscopic Colitis

• Registration Number: NCT05058131
• Lead Sponsor: Örebro University, Sweden

Brief Summary

This study examines how a fermentable dietary fibre known to promote butyrate production impacts intestinal barrier function, intestinal microbiota, intestinal inflammation, and gastrointestinal symptoms in patients with microscopic colitis.

Detailed Description

The study examines the effects of a 6-week supplementation period with a dietary fibre product (type of wheat bran) on intestinal barrier function, intestinal inflammation, intestinal microbiota, and gastrointestinal symptoms in patients with MC. The study subjects will consume the study products (placebo-fibre, butyrate-promoting fibre) as a powder supplemented to their daily habitual diet. A maltodextrin-based product is used as placebo. After giving their informed consent, the study subjects fill out a background questionnaire to assess their eligibility for the study (Visit 1). Participants deemed suitable for the study will be randomised into two study arms (placebo-fibre, butyrate-promoting fibre) before undergoing a baseline visit (Visit 2) before the start of the intervention period. After the 6-week intervention period, the participants will come back for a final visit (Visit 3). In vivo intestinal permeability will be measured using the standard multi-sugar test at visits 2 and 3. Blood and faecal samples will also be collected during visits 2 and 3. In addition to the visits described above, a subset of patients (max. 20) will undergo a colonoscopy before and at the end of the intervention period at Örebro University Hospital where an experienced gastroenterologist collects 16 colonic biopsies. These colonic biopsies are mounted in an Ussing chamber system to specifically study colonic permeability. During visits 2 and 3, the participants also complete questionnaires to assess their gastrointestinal symptoms, quality of life, physical activity, and dietary habits. During the study period, the participants will also keep a daily diary recording the number of diarrheal and loose stools. The participants are asked to maintain their habitual diet and lifestyle as well as not to consume probiotic or prebiotic supplements.

Study Timeline

• Study First Submitted: 2021-09-09
• Study First Submitted QC: 2021-09-16
• Study First Posted: 2021-09-27
• Study Start: 2021-11-03
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-20
• Last Update Posted: 2022-04-21
• Primary Completion: 2022-12-30
• Study Completion: 2022-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Signed informed consent
2. Diagnosis of microscopic colitis (collagenous or lymphocytic colitis)
3. Active disease with no medication (e.g. budesonide) or stable budesonide treatment with or without symptoms
4. Age between 18-75

Exclusion Criteria

1. Previous diagnosis of other organic gastrointestinal disease that interferes with the outcome parameters used in this study (e.g. ulcerative colitis)
2. Previous abdominal surgery which might influence gastrointestinal function, except appendectomy and cholecystectomy
3. History of or present gastrointestinal malignancy or polyposis
4. Diagnosis of gastrointestinal infection within the last 6 months
5. Current diagnosis of dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation
6. Chronic neurological/neurodegenerative disease (e.g. Parkinson's disease)
7. Autoimmune disease (e.g. rheumatoid arthritis)
8. Chronic pain syndromes (e.g. fibromyalgia)
9. Chronic fatigue syndrome
10. Severe endometriosis
11. Coeliac disease
12. Diagnosis of lactose intolerance within the last 3 months
13. Pregnancy or breast-feeding
14. Regular intake of anti-inflammatory and/or other immunosuppressive medication than budesonide within the last 3 months
15. Intake of proton pump inhibitors (e.g. omeprazol) within the last 4 weeks
16. Use of anti-depressants within the last 3 months
17. Regular intake of mast cell stabilizing drugs (e.g. sodium cromoglycate) within the last 3 months
18. Antimicrobial treatment within the last 12 weeks before baseline sampling
19. Antimicrobial prophylaxis (e.g. urinary tract infection)
20. Regular intake of probiotics, nutritional supplements, or herb products that might affect intestinal function within the last 4 weeks if the investigator considers that those could affect study outcome
21. Inability to maintain current diet and lifestyle during the study period
22. Alcohol or drug abuse
23. Any clinically significant present or past disease/condition which the investigator considers to possibly interfere with the study outcome

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Colonic permeability in vivo	6 weeks	Difference in urinary sucralose/erythritol excretion ratio between the study arms

Secondary Outcome Measures

Name	Time	Method
Composition of intestinal microbiota	6 weeks	Difference in the composition of intestinal microbiota between the study arms
Small intestinal permeability in vivo	6 weeks	Difference in urinary lactulose/rhamnose excretion ratio between the study arms
Colonic permeability ex vivo in Ussing chambers	6 weeks	Difference in the translocation of FITC-labeled dextran and horseradish peroxidase between the study arms
Concentrations of intestinal fatty-acid binding protein	6 weeks	Difference in plasma concentrations of intestinal fatty-acid binding protein between the study arms
Concentratios of faecal calprotectin	6 weeks	Difference in faecal levels of calprotectin between the study arms
Concentrations of faecal myeloperoxidase	6 weeks	Difference in faecal levels of myeloperoxidase between the study arms
Concentrations of high-sensitive C-reactive protein	6 weeks	Difference in plasma levels of high-sensitive C-reactive protein between the study arms
Concentrations of inflammatory cytokines	6 weeks	Difference in TNF-a, IFN-y, IL-1B, IL-4, IL-6, IL-8, IL-10 levels in serum between the study arms
Functionality of intestinal microbiota	6 weeks	Difference in the levels of intestinal microbiota -derived metabolites in the serum and faeces between the study arms
Concentrations of lipopolysaccharide-binding protein	6 weeks	Difference in plasma levels of lipopolysaccharide-binding protein between the study arms

Trial Locations

Locations (1)

Örebro University; 🇸🇪 Örebro, Örebro Län, Sweden