Faecal Microbiota Transplantation in Patients With Microscopic Colitis
Primary Purpose
Microscopic Colitis
Status
Completed
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
Faecal microbiota transfer (FMT)
Sponsored by
About this trial
This is an interventional treatment trial for Microscopic Colitis
Eligibility Criteria
Inclusion criteria for patients:
- Signed informed consent
- Active MC diagnosis, defined as >3 stools a day from which at least one should be watery
- Willingness to stop budesonide treatment during participation in the trial
- Age: 18-70 years
Exclusion criteria for patients
- Previous complicated gastrointestinal surgery
- Malignant disease except non-melanoma skin cancer
- Dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation
- C. difficile or other current gastroenteritis
- Females who are pregnant or breast-feeding
- Severe endometriosis
- Antimicrobial treatment 4 weeks prior to first screening visit
- Antimicrobial prophylaxis (eg. acne, urinary tract infection)
- Regular consumption of probiotic products 4 weeks prior to randomization
- Recently diagnosed lactose intolerance (less than 6 months prior to first screening visit)
- Recently diagnosed coeliac disease (less than 6 months prior to first screening visit)
- Regular intake of NSAIDs (non steroidal anti-inflammatory drugs)
- Abuse of alcohol or drugs
- Any clinically significant disease/condition which in the investigator's opinion could interfere with the results of the trial
Inclusion criteria for donors
- Signed informed consent
- High-butyrate producing microbiota in faecal samples
- Age: 18-65 years
Exclusion criteria for donors
- Known organic gastrointestinal disease (e.g. IBD, IBS, chronic diarrhoea or constipation)
- First degree relative with IBD
- History of or present gastrointestinal malignancy or polyposis
- Recent (gastrointestinal) infection (within last 6 months)
- History of major gastrointestinal surgery (e.g. gastric bypass)
- Eosinophilic disorders of the gastrointestinal tract
- Current communicable disease (e.g. upper respiratory tract infection)
- Malignant disease and/or patients who are receiving systemic anti-neoplastic agents
- Psychiatric diseases (e.g. dementia, depression, schizophrenia, autism, Asperger Syndrome) or other incapacity for adequate cooperation
- Chronic neurological/neurodegenerative diseases (e.g. Parkinson's disease, multiple sclerosis)
- Autoimmune disease and/or patients receiving immunosuppressive medications
- Major relevant allergies (e.g. food allergy, multiple allergies)
- Chronic pain syndromes (e.g. fibromyalgia)
- Chronic fatigue syndrome
- HIV, hepatitis A, B, C or known exposure within the recent 12 months
- Obesity (BMI>30) or metabolic syndrome
- Antimicrobial treatment or prophylaxis within the last 3 months
- Other chronic use of drugs that may affect the microbiome, e.g. proton pump inhibitors
- First degree relative with cardiovascular thrombosis before 50 years of age
- Females who are pregnant or breast-feeding
- Known clinically significant abnormal laboratory values
- Participation in high-risk sexual behaviours
- Abuse of alcohol or drugs
- Tattoo or body piercing within the last 6 months
- Travelling in countries with low hygiene or high infection risk for endemic diarrhoea within the last 6 months
- Positive stool testing for C. difficile, ova and parasites (e.g. Cyclospora, Isospora, Cryptosporidium), enteric pathogens (e.g. enterohaemorrhagic E. coli, Salmonella, Shigella, Yersinia, Campylobacter, Giarda antigen, amoebas)
- Positive stool testing for multiresistant bacteria (e.g. extended-spectrum beta- lactamase (ESBL) producing organisms, multi-resistant Gram-negative bacilli (MRGN) 3 and 4, vancomycin-resistant enterococci (VRE) or methicillin-resistant Staphylococcus aureus (MRSA))
- Calprotectin > 50 μg/g of faeces
- Positive blood testing for HIV, Hepatitis A, B, C, syphilis, Human T-lymphotropic virus (HTLV), cytomegalovirus (CMV) and Epstein Barr Virus (EBV)
- Any clinically significant disease/condition which in the investigator's opinion could interfere with the results of the trial
Sites / Locations
- University Hospital Örebro
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Faecal microbiota transfer (FMT)
Arm Description
Suspended stool from a healthy donor
Outcomes
Primary Outcome Measures
Proportion of MC patients in remission six weeks after the first FMT.
Remission is defined as <3 stools per day and a mean of less than one watery stool per day.
Secondary Outcome Measures
Changes in general health and symptom questionnaire scores
SHS
Changes in general health questionnaire scores
SF-36
Changes in quality of life questionnaire scores
EG-5D-5L
Changes in gastrointestinal symptom questionnaire scores
GSRS
Changes in hospital and anxiety depression scores
HADS
Changes in number and form of bowel movements
1-week-diaries
Changes in faecal and mucosal microbiota composition
16S rRNA-based next generation sequencing
Changes in lymphocyte infiltration
Immunohistochemistry and flow cytometry
Changes in subepithelial collagen layer
Immunohistochemistry
Changes in immune cell composition of colonic biopsies
Immunohistochemistry and flow cytometry
Full Information
NCT ID
NCT03275467
First Posted
August 28, 2017
Last Updated
February 20, 2020
Sponsor
Örebro University, Sweden
Collaborators
Region Örebro County
1. Study Identification
Unique Protocol Identification Number
NCT03275467
Brief Title
Faecal Microbiota Transplantation in Patients With Microscopic Colitis
Official Title
Faecal Microbiota Transplantation in Patients With Microscopic Colitis
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
June 1, 2017 (Actual)
Primary Completion Date
June 5, 2019 (Actual)
Study Completion Date
October 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Örebro University, Sweden
Collaborators
Region Örebro County
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Microscopic colitis (MC) is a disease with chronic inflammation of the colon that is mostly diagnosed in middle-aged or elderly women. Patients suffer from chronic watery diarrhoea, abdominal pain and weight loss. The aetiology of MC is still unknown but it is hypothesized that MC is caused by a deregulated immune response to a luminal agent in predisposed individuals, and an important role of the intestinal microbiota is suggested.
In the current proof-of-concept study, the effect of faecal microbiota transfer (FMT) in 10 MC patients will be evaluated. FMT consists in the infusion of suspended stool from a healthy donor into the intestine of a patient with the aim to restore a disturbed intestinal microbiota.
Detailed Description
This will be an intervention pilot study with a 12-week and an optional 6-months follow-up period. It will be investigated if the infusion of suspended stool from healthy donors improves the symptoms of MC patients by restoring their disturbed intestinal microbiota. This procedure is known as faecal microbiota transplantation (FMT).
MC patients (n=10) will be randomised to receive FMT using stool from one of two healthy donors.
At baseline, blood samples and mucosal biopsies will be obtained from the descending colon. In addition, faecal samples will be collected and patients will complete symptom questionnaires. The first FMT will be administered by colonoscopy, FMT 2-3 by enemas. Faecal samples will be collected and questionnaires will be completed at different time points during the study. The patients will be followed-up at 6 weeks, 8 weeks, 12 weeks and 6 months after receiving FMT 1, however, the follow-up after 6 months will be optional. Additional biopsies from the descending colon and blood samples will be collected 6 weeks after the first FMT.
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
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Faecal microbiota transfer (FMT)
Arm Type
Experimental
Arm Description
Suspended stool from a healthy donor
Intervention Type
Other
Intervention Name(s)
Faecal microbiota transfer (FMT)
Intervention Description
Suspended stool from a healthy donor
Primary Outcome Measure Information:
Title
Proportion of MC patients in remission six weeks after the first FMT.
Description
Remission is defined as <3 stools per day and a mean of less than one watery stool per day.
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Changes in general health and symptom questionnaire scores
Description
SHS
Time Frame
6 weeks, 8 weeks, 12 weeks, 6 months
Title
Changes in general health questionnaire scores
Description
SF-36
Time Frame
6 weeks, 8 weeks, 12 weeks, 6 months
Title
Changes in quality of life questionnaire scores
Description
EG-5D-5L
Time Frame
6 weeks, 8 weeks, 12 weeks, 6 months
Title
Changes in gastrointestinal symptom questionnaire scores
Description
GSRS
Time Frame
6 weeks, 8 weeks, 12 weeks, 6 months
Title
Changes in hospital and anxiety depression scores
Description
HADS
Time Frame
6 weeks, 8 weeks, 12 weeks, 6 months
Title
Changes in number and form of bowel movements
Description
1-week-diaries
Time Frame
6 weeks, 8 weeks, 12 weeks, 6 months
Title
Changes in faecal and mucosal microbiota composition
Description
16S rRNA-based next generation sequencing
Time Frame
faecal: 6 weeks, 8 weeks, 12 weeks, 6 months; mucosal: 6 weeks
Title
Changes in lymphocyte infiltration
Description
Immunohistochemistry and flow cytometry
Time Frame
6 weeks
Title
Changes in subepithelial collagen layer
Description
Immunohistochemistry
Time Frame
6 weeks
Title
Changes in immune cell composition of colonic biopsies
Description
Immunohistochemistry and flow cytometry
Time Frame
6 weeks
Other Pre-specified Outcome Measures:
Title
Changes in inflammation markers in faecal samples such as faecal calprotectin
Time Frame
6 weeks, 8 weeks, 12 weeks, 6 months
Title
Changes in metabolite profile in faecal samples and blood
Time Frame
faecal: 6 weeks, 8 weeks, 12 weeks, 6 months; blood: 6 weeks
Title
Changes in gene expression in mucosal biopsies
Time Frame
6 weeks
Title
Changes in barrier function markers in colonic biopsies
Time Frame
6 weeks
Title
Changes in gene expression of butyrate transporters in colonic biopsies
Time Frame
6 weeks
Title
Changes in markers of inflammation and intestinal barrier function in blood
Time Frame
6 weeks
Title
Changes in plasma levels of cardiovascular disease markers and platelet responsiveness and aggregation
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria for patients:
Signed informed consent
Active MC diagnosis, defined as >3 stools a day from which at least one should be watery
Willingness to stop budesonide treatment during participation in the trial
Age: 18-70 years
Exclusion criteria for patients
Previous complicated gastrointestinal surgery
Malignant disease except non-melanoma skin cancer
Dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation
C. difficile or other current gastroenteritis
Females who are pregnant or breast-feeding
Severe endometriosis
Antimicrobial treatment 4 weeks prior to first screening visit
Antimicrobial prophylaxis (eg. acne, urinary tract infection)
Regular consumption of probiotic products 4 weeks prior to randomization
Recently diagnosed lactose intolerance (less than 6 months prior to first screening visit)
Recently diagnosed coeliac disease (less than 6 months prior to first screening visit)
Regular intake of NSAIDs (non steroidal anti-inflammatory drugs)
Abuse of alcohol or drugs
Any clinically significant disease/condition which in the investigator's opinion could interfere with the results of the trial
Inclusion criteria for donors
Signed informed consent
High-butyrate producing microbiota in faecal samples
Age: 18-65 years
Exclusion criteria for donors
Known organic gastrointestinal disease (e.g. IBD, IBS, chronic diarrhoea or constipation)
First degree relative with IBD
History of or present gastrointestinal malignancy or polyposis
Recent (gastrointestinal) infection (within last 6 months)
History of major gastrointestinal surgery (e.g. gastric bypass)
Eosinophilic disorders of the gastrointestinal tract
Current communicable disease (e.g. upper respiratory tract infection)
Malignant disease and/or patients who are receiving systemic anti-neoplastic agents
Psychiatric diseases (e.g. dementia, depression, schizophrenia, autism, Asperger Syndrome) or other incapacity for adequate cooperation
Chronic neurological/neurodegenerative diseases (e.g. Parkinson's disease, multiple sclerosis)
Autoimmune disease and/or patients receiving immunosuppressive medications
Major relevant allergies (e.g. food allergy, multiple allergies)
Chronic pain syndromes (e.g. fibromyalgia)
Chronic fatigue syndrome
HIV, hepatitis A, B, C or known exposure within the recent 12 months
Obesity (BMI>30) or metabolic syndrome
Antimicrobial treatment or prophylaxis within the last 3 months
Other chronic use of drugs that may affect the microbiome, e.g. proton pump inhibitors
First degree relative with cardiovascular thrombosis before 50 years of age
Females who are pregnant or breast-feeding
Known clinically significant abnormal laboratory values
Participation in high-risk sexual behaviours
Abuse of alcohol or drugs
Tattoo or body piercing within the last 6 months
Travelling in countries with low hygiene or high infection risk for endemic diarrhoea within the last 6 months
Positive stool testing for C. difficile, ova and parasites (e.g. Cyclospora, Isospora, Cryptosporidium), enteric pathogens (e.g. enterohaemorrhagic E. coli, Salmonella, Shigella, Yersinia, Campylobacter, Giarda antigen, amoebas)
Positive stool testing for multiresistant bacteria (e.g. extended-spectrum beta- lactamase (ESBL) producing organisms, multi-resistant Gram-negative bacilli (MRGN) 3 and 4, vancomycin-resistant enterococci (VRE) or methicillin-resistant Staphylococcus aureus (MRSA))
Calprotectin > 50 μg/g of faeces
Positive blood testing for HIV, Hepatitis A, B, C, syphilis, Human T-lymphotropic virus (HTLV), cytomegalovirus (CMV) and Epstein Barr Virus (EBV)
Any clinically significant disease/condition which in the investigator's opinion could interfere with the results of the trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert J Brummer, Professor, MD
Organizational Affiliation
Örebro University, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Örebro
City
Örebro
State/Province
Örebro County
ZIP/Postal Code
70185
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
No
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Faecal Microbiota Transplantation in Patients With Microscopic Colitis
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