Effects of Faecal Microbiota Transplantation in Patients With IBS
Condition: Irritable Bowel Syndrome
MeSH terms: Irritable Bowel Syndrome; Syndrome
Study type: Interventional

Summary: 
      Irritable bowel syndrom (IBS) is a common chronic gastrointestinal disorder that affects
      10-20% of the world population. The prevalence of IBS in Norway is between 8% and 25%. The
      pathophysiology of IBS is incompletely understood, and there is no effective treatment for
      this condition. Imbalance (dysbiosis) of the gut microbiome has been found in patients with
      IBS. In the absence of effective method to restore the dysbiosis, transplantation of a
      microbiome from healthy individuals with well-functioning gut (FMT) to those with IBS has
      been performed. Two randomized double blind placebo-controlled (RCT) studies have been
      published recently. Whereas it was reported in one study that FMT reduced symptom and
      improved quality of life in patients with IBS, FMT had no effect in the other study. In order
      to clarify these contradictory results, a new RCT study that enrolled larger number of
      patients is required. In this study, the investigators intend to recruit 170 IBS patients
      from those attending outdoor clinic at Stord hospital in a randomized, double blind placebo
      trial. A single healthy donor with well-characterized microbiome is going to be used. The
      effects on symptoms, quality of life, fatigue as well as dysbiosis before and after FMT are
      going to be investigated. The possible mechanisms behind the effects if any of FMT such as
      changes in intestinal stem cells, enteroendocrine cells and local immune defense shall be
      also investigated. The patients are going to be randomized either to placebo (own faces), 30
      g or 60 g of the donor faces in ratio 1:1:1.
    

Detailed description: 
      Study design Patients One hundred and seventy patients who fulfill the following inclusion
      criteria and lack the exclusion criteria shall be included. In addition, the patients are
      examined physically, and blood tests are taken to exclude inflammation, and liver, kidney and
      thyroid diseases. They undergo further gastroscopy with duodenal biopsies to exclude coeliac
      disease. They undergo also colonoscopy to exclude malignity, or inflammatory bowel disease
      (IBD). Microscopic colitis is excluded by examining tissue obtained by colonoscopy with
      segmental biopsy sampling.

      Donor selection and screening:

      A single donor shall be selected and screened according to the European and international
      guidelines. The donor should not be a first-degree relative to any of the patients, as the
      intestinal microbiota is affected by the genetic composition, and similarity between the
      donor and recipient in the fecal microbiota may occur.

      Protocol

      Feces collection, preparation and administration:

      Feces from both the donors and recipients were collected and stored at - 80•. Frozen feces
      (30 or 60g) from the donor or patients (placebo), thawed at 5° C and were dissolved in 50 mL
      of 0.9% sterile saline per 30 g feces. The dissolved stool is administrated to the patients,
      after overnight fast, through working channel of gastroduodeno-scope in pars descendent
      duodenum distal to the papilla of Vater.

      Sigmoidoscopy: After administration of faeces, a sigmoidoscopy is performed during which 4
      biopsies from the sigmoid colon about 30 cm from anus, and 4 biopsies from the rectum about
      15 cm from anus are taken. Sigmoidoscopy is repeated in the same way 1 month after FMT.

      Methods Questionnaires

        1. IBS symptom severity Scale (IBS-SSS) questionnaire.

        2. Birmingham Symptom scale questionnaires.

        3. IBSQoL questionnaire.

        4. Short form of Nepean Dyspepsia Index (SF-NDI) questionnaire.

        5. Fatigue Assessment Scale (FAS).

      Microbiome analysis Gut microbiota analysis was performed using the GA-mapTM Dysbiosis test
      (Genetic Analysis AS, Oslo, Norway) by algorithmically assessing fecal bacterial abundance
      and profile (dysbiosis index, DI), and potential deviation in the microbiome from
      normobiosis. GA-map test is based on fecal homogenization, mechanical bacterial cell
      disruption and automated total bacterial genomic DNA extraction using magnetic beads. DI is
      based on 54 DNA probes targeting more than 300 bacterial strains based on their 16S rRNA
      sequence in seven variable regions (V3-V9). Twenty-six bacteria probes are species specific,
      19 detect bacteria on genus level, and 9 probes detect bacteria at higher taxonomic levels.
      Probe labeling is by single nucleotide extension and hybridization to complementary probes
      coupled to magnetic beads, and signal detection by using Bio Code 1000A 128-Plex Analyzer
      (Applied Bio Code, Santa Fe Springs, CA, USA). A DI above 2 shows a microbiota profile that
      differs from that of the normobiotic reference collection (DI 1-2: non-dysbiosis, DI:
      moderate, DI 4-5: severe dysbiosis).
    

Intervention name(s): healthy feces microbiota
Intervention type(s): Dietary Supplement
Intervention description(s): Suspension of healthy feces microbiota in sterile saline solution
Other intervention name(s): placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Intervention. Dietary supplement: fecal suspension. Healthy donor or own faeces (placebo) administrated through working canal of a gastroscope.
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment