Faecal Microbiota Transplantation in the Treatment of Chronic Pouchitis (MicroPouch)
The Effect of Faecal Microbiota Transplantation in the Treatment of Chronic Pouchitis: A Multicentre, Placebo-controlled, Randomized, Double Blinded Trial
Patients with the chronic bowel disease pouchitis is disabled by bloody diarrhoea and abdominal pain often followed by fever. Pouchitis is an inflammation in a pouch, a reservoir formed by the small intestine in the management of the chronic inflammatory bowel disease, ulcerative colitis. Chronic pouchitis is a rare disease with a prevalence in Denmark of <1.8 per 10,000 people, mostly younger people (<50 years). The standard treatment for pouchitis is intensive broad-spectrum antibiotics for a longer period. However, the treatment often fails after repeated treatments. Recent studies show that patients with pouchitis have an altered composition of the gut flora, called microbiota, compared to healthy individuals. As shown by several studies, faecal microbiota transplantation (FMT) with administration of faeces from healthy donors can alter the microbiota. Treatment with faecal microbiota transplantation is today known to be the ultimate treatment for antibiotic resistant recurrent bowel infection with the bacteria Clostridium difficile. It is however still uncertain if faecal microbiota transplantation can be used to the treatment of chronic pouchitis.
The study primary aims to investigate if transplantation of faeces from healthy donors administrated as enemas to patients with chronic pouchitis is superior to placebo for the treatment of pouchitis.
The project is designed as a multi-center, double-blinded, randomized, placebo-controlled treatment study. A positive result from the project will result in an improved treatment to pouchitis patients. Moreover, repeated long-lasting broad-spectrum treatments with antibiotic, which carry a high risk of antibiotic resistance in the society, will be avoided.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Réel)
Phase
- N'est pas applicable
Contacts et emplacements
Lieux d'étude
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-
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Aalborg, Danemark, 9000
- Department of Gastrointestinal Surgery, Aalborg University Hospital
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Hvidovre, Danemark, 2650
- Department of Medical Gastroenterology, Copenhagen University Hospital Hvidovre
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Double
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Comparateur actif: FMT
Faecal microbiota transplantation
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FMT par lavement quotidien avec les fèces du donneur
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Comparateur placebo: Placebo
Placebo mixture
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Placebo by daily enema with placebo mixture
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Nombre de patients obtenant une rémission clinique évalué par le PDAI
Délai: 4 semaines
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La rémission clinique est définie comme PDAI<7
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4 semaines
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Nombre de patients obtenant une réponse clinique évaluée par PDAI
Délai: 4 semaines
|
La réponse clinique est définie comme une réduction du score PDAI> 2
|
4 semaines
|
|
Number of patients experience improvement in quality of life assessed by the patient-reported questionnaire SIBDQ
Délai: 4 weeks
|
4 weeks
|
|
|
Number of patients relapsing
Délai: 12 months
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Relapse is defined as need for antibiotic treatment for pouchitis
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12 months
|
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Number of patients with treatment-related adverse events in the FMT group compared to the placebo group
Délai: 12 months
|
12 months
|
|
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Increase of the faecal microbiota biodiversity assessed by alpha-diversity
Délai: 12 months
|
12 months
|
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Engraftment of the donor microbiota in the patients assessed by beta-diversity
Délai: 12 months
|
12 months
|
Collaborateurs et enquêteurs
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- MicroPouch
Plan pour les données individuelles des participants (IPD)
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Informations sur les médicaments et les dispositifs, documents d'étude
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