Back to resultsModulation of Intestinal Barrier Function and Inflammation Via Butyrate-promoting Dietary Fibre
Primary Purpose
Microscopic Colitis
Status
Recruiting
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
Dietary fibre
Placebo compound
Sponsored by
About this trial
This is an interventional basic science trial for Microscopic Colitis
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent
- Diagnosis of microscopic colitis (collagenous or lymphocytic colitis)
- Active disease with no medication (e.g. budesonide) or stable budesonide treatment with or without symptoms
- Age between 18-75
Exclusion Criteria:
- Previous diagnosis of other organic gastrointestinal disease that interferes with the outcome parameters used in this study (e.g. ulcerative colitis)
- Previous abdominal surgery which might influence gastrointestinal function, except appendectomy and cholecystectomy
- History of or present gastrointestinal malignancy or polyposis
- Diagnosis of gastrointestinal infection within the last 6 months
- Current diagnosis of dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation
- Chronic neurological/neurodegenerative disease (e.g. Parkinson's disease)
- Autoimmune disease (e.g. rheumatoid arthritis)
- Chronic pain syndromes (e.g. fibromyalgia)
- Chronic fatigue syndrome
- Severe endometriosis
- Coeliac disease
- Diagnosis of lactose intolerance within the last 3 months
- Pregnancy or breast-feeding
- Regular intake of anti-inflammatory and/or other immunosuppressive medication than budesonide within the last 3 months
- Intake of proton pump inhibitors (e.g. omeprazol) within the last 4 weeks
- Use of anti-depressants within the last 3 months
- Regular intake of mast cell stabilizing drugs (e.g. sodium cromoglycate) within the last 3 months
- Antimicrobial treatment within the last 12 weeks before baseline sampling
- Antimicrobial prophylaxis (e.g. urinary tract infection)
- 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
- Inability to maintain current diet and lifestyle during the study period
- Alcohol or drug abuse
- Any clinically significant present or past disease/condition which the investigator considers to possibly interfere with the study outcome
Sites / Locations
- Örebro UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Dietary fibre
Placebo compound
Arm Description
Butyrate-promoting dietary fibre
Placebo compound
Outcomes
Primary Outcome Measures
Colonic permeability in vivo
Difference in urinary sucralose/erythritol excretion ratio between the study arms
Secondary Outcome Measures
Small intestinal permeability in vivo
Difference in urinary lactulose/rhamnose excretion ratio between the study arms
Colonic permeability ex vivo in Ussing chambers
Difference in the translocation of FITC-labeled dextran and horseradish peroxidase between the study arms
Concentrations of intestinal fatty-acid binding protein
Difference in plasma concentrations of intestinal fatty-acid binding protein between the study arms
Concentrations of lipopolysaccharide-binding protein
Difference in plasma levels of lipopolysaccharide-binding protein between the study arms
Concentratios of faecal calprotectin
Difference in faecal levels of calprotectin between the study arms
Concentrations of faecal myeloperoxidase
Difference in faecal levels of myeloperoxidase between the study arms
Concentrations of high-sensitive C-reactive protein
Difference in plasma levels of high-sensitive C-reactive protein between the study arms
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
Composition of intestinal microbiota
Difference in the composition of intestinal microbiota between the study arms
Functionality of intestinal microbiota
Difference in the levels of intestinal microbiota -derived metabolites in the serum and faeces between the study arms
Full Information
NCT ID
NCT05058131
First Posted
September 9, 2021
Last Updated
April 20, 2022
Sponsor
Örebro University, Sweden
1. Study Identification
Unique Protocol Identification Number
NCT05058131
Brief Title
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
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 3, 2021 (Actual)
Primary Completion Date
December 30, 2022 (Anticipated)
Study Completion Date
December 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Örebro University, Sweden
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Microscopic Colitis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dietary fibre
Arm Type
Active Comparator
Arm Description
Butyrate-promoting dietary fibre
Arm Title
Placebo compound
Arm Type
Placebo Comparator
Arm Description
Placebo compound
Intervention Type
Dietary Supplement
Intervention Name(s)
Dietary fibre
Intervention Description
Dietary fibre as a powder, 24 g per day for 6 weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo compound
Intervention Description
Maltodextrin powder, 24 g per day for 6 weeks
Primary Outcome Measure Information:
Title
Colonic permeability in vivo
Description
Difference in urinary sucralose/erythritol excretion ratio between the study arms
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Small intestinal permeability in vivo
Description
Difference in urinary lactulose/rhamnose excretion ratio between the study arms
Time Frame
6 weeks
Title
Colonic permeability ex vivo in Ussing chambers
Description
Difference in the translocation of FITC-labeled dextran and horseradish peroxidase between the study arms
Time Frame
6 weeks
Title
Concentrations of intestinal fatty-acid binding protein
Description
Difference in plasma concentrations of intestinal fatty-acid binding protein between the study arms
Time Frame
6 weeks
Title
Concentrations of lipopolysaccharide-binding protein
Description
Difference in plasma levels of lipopolysaccharide-binding protein between the study arms
Time Frame
6 weeks
Title
Concentratios of faecal calprotectin
Description
Difference in faecal levels of calprotectin between the study arms
Time Frame
6 weeks
Title
Concentrations of faecal myeloperoxidase
Description
Difference in faecal levels of myeloperoxidase between the study arms
Time Frame
6 weeks
Title
Concentrations of high-sensitive C-reactive protein
Description
Difference in plasma levels of high-sensitive C-reactive protein between the study arms
Time Frame
6 weeks
Title
Concentrations of inflammatory cytokines
Description
Difference in TNF-a, IFN-y, IL-1B, IL-4, IL-6, IL-8, IL-10 levels in serum between the study arms
Time Frame
6 weeks
Title
Composition of intestinal microbiota
Description
Difference in the composition of intestinal microbiota between the study arms
Time Frame
6 weeks
Title
Functionality of intestinal microbiota
Description
Difference in the levels of intestinal microbiota -derived metabolites in the serum and faeces between the study arms
Time Frame
6 weeks
Other Pre-specified Outcome Measures:
Title
Faecal output measured by a daily diary
Description
Difference in the number of diarrhoeal stools per day between the study arms
Time Frame
6 weeks
Title
Gastrointestinal symptoms measured by Gastrointestinal Symptom Rating Scale
Description
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)
Time Frame
6 weeks
Title
Quality of life measured by EQ-5D-5L questionnaire
Description
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)
Time Frame
6 weeks
Title
Anxiety and depression measured by Hospital Anxiety and Depression Scale
Description
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)
Time Frame
6 weeks
Title
General well-being measured by Short Health Scale
Description
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)
Time Frame
6 weeks
Title
Concentrations of systemic and faecal markers of oxidative stress
Description
Difference in blood and faecal markers of oxidative stress (e.g. glutathione) between the study arms
Time Frame
6 weeks
Title
Concentrations of faecal chromogranins
Description
Difference in faecal levels of chromogranins between the study arms
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent
Diagnosis of microscopic colitis (collagenous or lymphocytic colitis)
Active disease with no medication (e.g. budesonide) or stable budesonide treatment with or without symptoms
Age between 18-75
Exclusion Criteria:
Previous diagnosis of other organic gastrointestinal disease that interferes with the outcome parameters used in this study (e.g. ulcerative colitis)
Previous abdominal surgery which might influence gastrointestinal function, except appendectomy and cholecystectomy
History of or present gastrointestinal malignancy or polyposis
Diagnosis of gastrointestinal infection within the last 6 months
Current diagnosis of dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation
Chronic neurological/neurodegenerative disease (e.g. Parkinson's disease)
Autoimmune disease (e.g. rheumatoid arthritis)
Chronic pain syndromes (e.g. fibromyalgia)
Chronic fatigue syndrome
Severe endometriosis
Coeliac disease
Diagnosis of lactose intolerance within the last 3 months
Pregnancy or breast-feeding
Regular intake of anti-inflammatory and/or other immunosuppressive medication than budesonide within the last 3 months
Intake of proton pump inhibitors (e.g. omeprazol) within the last 4 weeks
Use of anti-depressants within the last 3 months
Regular intake of mast cell stabilizing drugs (e.g. sodium cromoglycate) within the last 3 months
Antimicrobial treatment within the last 12 weeks before baseline sampling
Antimicrobial prophylaxis (e.g. urinary tract infection)
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
Inability to maintain current diet and lifestyle during the study period
Alcohol or drug abuse
Any clinically significant present or past disease/condition which the investigator considers to possibly interfere with the study outcome
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Richard A Forsgård, PhD
Phone
0790614037
Ext
+46
Email
richard.forsgard@oru.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert J Brummer, MD, PhD
Organizational Affiliation
Örebro University, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Örebro University
City
Örebro
State/Province
Örebro Län
ZIP/Postal Code
703 62
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richard A Forsgård, PhD
Phone
0790614037
Ext
+46
Email
richard.forsgard@oru.se
First Name & Middle Initial & Last Name & Degree
Robert J Brummer, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Modulation of Intestinal Barrier Function and Inflammation Via Butyrate-promoting Dietary Fibre
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