Clinical trial NCT05058131: Modulation of Intestinal Barrier Function and Inflammation Via Butyrate-promoting Dietary Fibre
Official title: The Effects of Fermentable Dietary Fibre Supplementation on Intestinal Permeability and Inflammation in Microscopic Colitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Microscopic Colitis
Lead sponsor: Örebro University, Sweden
Sponsor class: OTHER
First posted: 2021-09-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Colonic permeability in vivo
timeFrame: 6 weeks
Secondary outcomes:
measure: Small intestinal permeability in vivo
timeFrame: 6 weeks
measure: Colonic permeability ex vivo in Ussing chambers
timeFrame: 6 weeks
measure: Concentrations of intestinal fatty-acid binding protein
timeFrame: 6 weeks
measure: Concentrations of lipopolysaccharide-binding protein
timeFrame: 6 weeks
measure: Concentratios of faecal calprotectin
timeFrame: 6 weeks
measure: Concentrations of faecal myeloperoxidase
timeFrame: 6 weeks
measure: Concentrations of high-sensitive C-reactive protein
timeFrame: 6 weeks
measure: Concentrations of inflammatory cytokines
timeFrame: 6 weeks
measure: Composition of intestinal microbiota
timeFrame: 6 weeks
measure: Functionality of intestinal microbiota
timeFrame: 6 weeks
Other outcomes:
measure: Faecal output measured by a daily diary
timeFrame: 6 weeks
measure: Gastrointestinal symptoms measured by Gastrointestinal Symptom Rating Scale
timeFrame: 6 weeks
measure: Quality of life measured by EQ-5D-5L questionnaire
timeFrame: 6 weeks
measure: Anxiety and depression measured by Hospital Anxiety and Depression Scale
timeFrame: 6 weeks
measure: General well-being measured by Short Health Scale
timeFrame: 6 weeks
measure: Concentrations of systemic and faecal markers of oxidative stress
timeFrame: 6 weeks
measure: Concentrations of faecal chromogranins
timeFrame: 6 weeks
Locations:
city: Örebro
country: Sweden
facility: Örebro University
state: Örebro Län
Study officials:
affiliation: Örebro University, Sweden
name: Robert J Brummer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: