Faecal Microbiota Transplantation in the Treatment of Chronic Pouchitis
Klíčová slova
Abstraktní
Popis
Hypothesis:
Gut dysbiosis plays a significant causal role in chronic pouchitis. Modulating the gut microbiota using FMT has a clinical effect by inducing clinical remission in patients with chronic pouchitis.
Objective of the study:
The aim of the MicroPouch-trial is to investigate if transplantation (FMT) of faeces from healthy donors to patients with chronic pouchitis is clinical significant to placebo for the treatment of pouchitis.
Study design:
The project is designed as a multi-center, double-blinded, randomized, placebo-controlled treatment study.
Methods:
Faecal microbiota transplantation is performed with faeces from healthy donors. Potential donors are recruited from the Danish Blood Bank. They are screened for a various of infectious diseases by serum analysis (haematology, inflammation, liver and kidney function, HIV, Hepatitis, Cytomegalovirus, Epstein Barr virus and HbA1c) and faeces analysis (calprotectin, Clostridium difficile (PCR), enteric pathogenic bacteria and antibiotic-resistant bacteria, parasites, cysts, and viruses). Furthermore, the potential donors will complete an extensive questionnaire regarding general health, risk factors and medical history, before they can be included as faecal donors in the project. The screening procedure is based on recommendation from the European FMT Working Group.
The transplantation is performed by enemas, which contain either faeces from the faecal donors or placebo.
Initial before the treatment with either donor faeces or placebo, the patient will be invited for serum analysis (CRP, leukocytes) and faecal analysis (calprotectin, Clostridium difficile, enteric pathogenic bacteria), followed by a pouchoscopy with collection of biopsies. Materials from serum- and faecal analysis and biopsies will be stored for later analysis purpose. The patient will further complete questionnaires concerning symptoms and quality of life. The stage of disease will be evaluated based on the acknowledged questionnaire for pouchitis called Pouchitis Disease Activity Index (PDAI) score.
The treatment begins after all the initial examinations, and the patient will be treated during one month. The treatment consists of daily enema infusion, which either contain faeces from the faecal donors or placebo. During the treatment, the patient will daily record symptoms related to pouchitis (diarrhea, abdominal pain, bleeding per rectum, fever, general discomfort) and possible adverse effects to the treatment.
At the end of treatment, the patient will meet to a follow-up examination including serum analysis (CRP, leukocytes) and faecal analysis (calprotectin), pouchoscopy incl. biopsies, and the questionnaires applied before the treatment. Materials from serum- and faecal analysis and biopsies will be stored for later analysis.
The patient will be followed up with serum- and faecal analysis and pouchoscopy after additional 6 and 12 months to evaluate the long term effect of the transplantation. The consumption of antibiotics during the first year will be recorded. In case of lacking effect of faecal microbiota transplantation, the patient is offered standard antibiotic treatment for pouchitis, and will leave the study.
Faecal samples and biopsies collected in the study will be analyzed for the composition of the microbiota.
Termíny
| Poslední ověření: | 11/30/2019 |
| První předloženo: | 09/11/2019 |
| Odhadovaná registrace vložena: | 09/19/2019 |
| První zveřejnění: | 09/23/2019 |
| Poslední aktualizace byla odeslána: | 12/08/2019 |
| Poslední aktualizace zveřejněna: | 12/09/2019 |
| Aktuální datum zahájení studie: | 06/30/2019 |
| Odhadované datum dokončení primární: | 12/29/2020 |
| Odhadované datum dokončení studie: | 06/29/2021 |
Stav nebo nemoc
Intervence / léčba
Other: FMT
Other: Placebo
Fáze
Skupiny zbraní
| Paže | Intervence / léčba |
|---|---|
| Active Comparator: FMT Faecal microbiota transplantation | Other: FMT FMT by daily enema with donor faeces |
| Placebo Comparator: Placebo Placebo mixture | Other: Placebo Placebo by daily enema with placebo mixture |
Kritéria způsobilosti
| Věky způsobilé ke studiu | 18 Years Na 18 Years |
| Pohlaví způsobilá ke studiu | All |
| Přijímá zdravé dobrovolníky | Ano |
| Kritéria | Inclusion Criteria: - Patients ≥ 18 years of age with a J-pouch - PDAI ≥ 7 - Established diagnosis of chronic pouchitis (≥3 times of pouchitis within the last year, symptoms more than 4 weeks despite antibiotic treatment) - Antibiotic treatment for pouchitis (ciprofloxacin and/or metronidazole) within the last year - Not pregnant or breastfeeding Exclusion Criteria: - Immunosuppression - Pregnancy - Evidence of intestinal pathogen bacteria in the stool at inclusion visit - Any severe or newly diagnosed concomitant cardiovascular, hepatic, intestinal, renal, endocrine, pulmonary, dental disease with inflammation or psychiatric disorder, which, in the opinion of the investigator, might have an influence on the patient's compliance or the interpretation of the results - Probiotic intake within the last 2 weeks prior to study intervention - Participation in another clinical trial within the previous 30 days before baseline - Serious food allergies with earlier anaphylactic reactions |
Výsledek
Primární výsledná opatření
1. Number of patients achieving clinical remission assessed by PDAI [4 weeks]
Měření sekundárních výsledků
1. Number of patients achieving clinical response assessed by PDAI [4 weeks]
2. Number of patients experience improvement in quality of life assessed by the patient-reported questionnaire SIBDQ [4 weeks]
3. Number of patients relapsing [12 months]
4. Number of patients with treatment-related adverse events in the FMT group compared to the placebo group [12 months]
5. Increase of the faecal microbiota biodiversity assessed by alpha-diversity [12 months]
6. Engraftment of the donor microbiota in the patients assessed by beta-diversity [12 months]
