Microscopic Colitis
Conditions
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.
Interventions
DIETARY_SUPPLEMENTDietary fibre
Dietary fibre as a powder, 24 g per day for 6 weeks
DIETARY_SUPPLEMENTPlacebo compound
Maltodextrin powder, 24 g per day for 6 weeks
Sponsors
Örebro University, Sweden
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Colonic permeability in vivo | 6 weeks | Difference in urinary sucralose/erythritol excretion ratio between the study arms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of intestinal fatty-acid binding protein | 6 weeks | Difference in plasma concentrations of intestinal fatty-acid binding protein between the study arms |
| Concentrations of lipopolysaccharide-binding protein | 6 weeks | Difference in plasma levels of lipopolysaccharide-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 |
| Composition of intestinal microbiota | 6 weeks | Difference in the composition of intestinal microbiota 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 |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quality of life measured by EQ-5D-5L questionnaire | 6 weeks | Difference in the scores of the quality of life between the study arms (Visual Analog Scale 0-100, lower value corresponds to a worse outcome) |
| Anxiety and depression measured by Hospital Anxiety and Depression Scale | 6 weeks | Difference in the scores of anxiety and depression between the study arms (depression and anxiety scores separately, 7 questions each with a scale of 0-3, minimum score 0, maximum score 21 in both, higher value corresponds to a worse outcome) |
| General well-being measured by Short Health Scale | 6 weeks | Difference in the scores of general well-being between the study arms (4 questions with a scale of 1-7, higher scores correspond to a worse outcome) |
| Concentrations of systemic and faecal markers of oxidative stress | 6 weeks | Difference in blood and faecal markers of oxidative stress (e.g. glutathione) between the study arms |
| Concentrations of faecal chromogranins | 6 weeks | Difference in faecal levels of chromogranins between the study arms |
| Faecal output measured by a daily diary | 6 weeks | Difference in the number of diarrhoeal stools per day between the study arms |
| Gastrointestinal symptoms measured by Gastrointestinal Symptom Rating Scale | 6 weeks | Difference in the frequency and severity of gastrointestinal symptoms between the study arms (15 questions with a scale of 1-7, minimum value 1, maximum 7, higher score correspond to a worse outcome) |
Countries
Sweden
Contacts
Primary ContactRichard A Forsgård, PhD
Outcome results
None listed