Microscopic Colitis
Conditions
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.
Interventions
OTHERFaecal microbiota transfer (FMT)
Suspended stool from a healthy donor
Sponsors
Region Örebro County
Örebro University, Sweden
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
for patients: 1. Signed informed consent 2. Active MC diagnosis, defined as \>3 stools a day from which at least one should be watery 3. Willingness to stop budesonide treatment during participation in the trial 4. Age: 18-70 years
Exclusion criteria
for patients 1. Previous complicated gastrointestinal surgery 2. Malignant disease except non-melanoma skin cancer 3. Dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation 4. C. difficile or other current gastroenteritis 5. Females who are pregnant or breast-feeding 6. Severe endometriosis 7. Antimicrobial treatment 4 weeks prior to first screening visit 8. Antimicrobial prophylaxis (eg. acne, urinary tract infection) 9. Regular consumption of probiotic products 4 weeks prior to randomization 10. Recently diagnosed lactose intolerance (less than 6 months prior to first screening visit) 11. Recently diagnosed coeliac disease (less than 6 months prior to first screening visit) 12. Regular intake of NSAIDs (non steroidal anti-inflammatory drugs) 13. Abuse of alcohol or drugs 14. Any clinically significant disease/condition which in the investigator's opinion could interfere with the results of the trial Inclusion criteria for donors 1. Signed informed consent 2. High-butyrate producing microbiota in faecal samples 3. Age: 18-65 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of MC patients in remission six weeks after the first FMT. | 6 weeks | Remission is defined as \<3 stools per day and a mean of less than one watery stool per day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in gastrointestinal symptom questionnaire scores | 6 weeks, 8 weeks, 12 weeks, 6 months | GSRS |
| Changes in hospital and anxiety depression scores | 6 weeks, 8 weeks, 12 weeks, 6 months | HADS |
| Changes in number and form of bowel movements | 6 weeks, 8 weeks, 12 weeks, 6 months | 1-week-diaries |
| Changes in general health and symptom questionnaire scores | 6 weeks, 8 weeks, 12 weeks, 6 months | SHS |
| Changes in faecal and mucosal microbiota composition | faecal: 6 weeks, 8 weeks, 12 weeks, 6 months; mucosal: 6 weeks | 16S rRNA-based next generation sequencing |
| Changes in lymphocyte infiltration | 6 weeks | Immunohistochemistry and flow cytometry |
| Changes in subepithelial collagen layer | 6 weeks | Immunohistochemistry |
| Changes in immune cell composition of colonic biopsies | 6 weeks | Immunohistochemistry and flow cytometry |
| Changes in general health questionnaire scores | 6 weeks, 8 weeks, 12 weeks, 6 months | SF-36 |
| Changes in quality of life questionnaire scores | 6 weeks, 8 weeks, 12 weeks, 6 months | EG-5D-5L |
Other
| Measure | Time frame |
|---|---|
| Changes in gene expression in mucosal biopsies | 6 weeks |
| Changes in barrier function markers in colonic biopsies | 6 weeks |
| Changes in gene expression of butyrate transporters in colonic biopsies | 6 weeks |
| Changes in markers of inflammation and intestinal barrier function in blood | 6 weeks |
| Changes in plasma levels of cardiovascular disease markers and platelet responsiveness and aggregation | 6 weeks |
| Changes in inflammation markers in faecal samples such as faecal calprotectin | 6 weeks, 8 weeks, 12 weeks, 6 months |
| Changes in metabolite profile in faecal samples and blood | faecal: 6 weeks, 8 weeks, 12 weeks, 6 months; blood: 6 weeks |
Countries
Sweden
Outcome results
None listed