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

Microscopic Colitis Clinical Trial

Official title:

The Effects of Fermentable Dietary Fibre Supplementation on Intestinal Permeability and Inflammation in Microscopic Colitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05058131
• Other study ID #: MC-DF
• Status: Recruiting
• Phase: N/A
• Start date: November 3, 2021
• Est. completion date: December 30, 2022

Study information

• Verified date: April 2022
• Source: Örebro University, Sweden
• Contact: Richard A Forsgård, PhD
• Phone: 0790614037
• Email: richard.forsgard[@]oru.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 30, 2022
• Est. primary completion date: December 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Microscopic
• Inflammation
• Microscopic Colitis

Intervention

Dietary Supplement:
• Dietary fibre
Dietary fibre as a powder, 24 g per day for 6 weeks
• Placebo compound
Maltodextrin powder, 24 g per day for 6 weeks

Locations

Country	Name	City	State
Sweden	Örebro University	Örebro	Örebro Län

Sponsors (1)

Lead Sponsor	Collaborator
Örebro University, Sweden

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Faecal output measured by a daily diary	Difference in the number of diarrhoeal stools per day between the study arms	6 weeks
Other	Gastrointestinal symptoms measured by Gastrointestinal Symptom Rating Scale	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)	6 weeks
Other	Quality of life measured by EQ-5D-5L questionnaire	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)	6 weeks
Other	Anxiety and depression measured by Hospital Anxiety and Depression Scale	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)	6 weeks
Other	General well-being measured by Short Health Scale	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)	6 weeks
Other	Concentrations of systemic and faecal markers of oxidative stress	Difference in blood and faecal markers of oxidative stress (e.g. glutathione) between the study arms	6 weeks
Other	Concentrations of faecal chromogranins	Difference in faecal levels of chromogranins between the study arms	6 weeks
Primary	Colonic permeability in vivo	Difference in urinary sucralose/erythritol excretion ratio between the study arms	6 weeks
Secondary	Small intestinal permeability in vivo	Difference in urinary lactulose/rhamnose excretion ratio between the study arms	6 weeks
Secondary	Colonic permeability ex vivo in Ussing chambers	Difference in the translocation of FITC-labeled dextran and horseradish peroxidase between the study arms	6 weeks
Secondary	Concentrations of intestinal fatty-acid binding protein	Difference in plasma concentrations of intestinal fatty-acid binding protein between the study arms	6 weeks
Secondary	Concentrations of lipopolysaccharide-binding protein	Difference in plasma levels of lipopolysaccharide-binding protein between the study arms	6 weeks
Secondary	Concentratios of faecal calprotectin	Difference in faecal levels of calprotectin between the study arms	6 weeks
Secondary	Concentrations of faecal myeloperoxidase	Difference in faecal levels of myeloperoxidase between the study arms	6 weeks
Secondary	Concentrations of high-sensitive C-reactive protein	Difference in plasma levels of high-sensitive C-reactive protein between the study arms	6 weeks
Secondary	Concentrations of inflammatory cytokines	Difference in TNF-a, IFN-y, IL-1B, IL-4, IL-6, IL-8, IL-10 levels in serum between the study arms	6 weeks
Secondary	Composition of intestinal microbiota	Difference in the composition of intestinal microbiota between the study arms	6 weeks
Secondary	Functionality of intestinal microbiota	Difference in the levels of intestinal microbiota -derived metabolites in the serum and faeces between the study arms	6 weeks