Clinical trial NCT03822299: Effects of Faecal Microbiota Transplantation in Patients With IBS
Official title: Effects of Faecal Microbiota Transplantation in Patients With Irritable Bowel Syndrome: A Randomised, Double-blind Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Lead sponsor: Helse Fonna
Sponsor class: OTHER
Collaborators: name: Helse Vest
First posted: 2019-01-30
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Intervention. Dietary supplement: fecal suspension. Healthy donor or own faeces (placebo) administrated through working canal of a gastroscope.
Primary purpose: TREATMENT

Brief 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).

Eligibility criteria: Inclusion criteria:

1. Patients between who fulfill Rome IV criteria for the diagnosis of IBS.
2. Patients with moderate to severe IBS symptoms (IBS-SSS ≥ 175).

Exclusion criteria:

1. Pregnant, planning pregnancy or lactating women.
2. The use of antibiotics or probiotics within 1 month prior to FMT.
3. Patients who had undergone any abdominal surgery, with the exception of appendectomy, cholecystectomy, Caesarean section or hysterectomy.

Primary outcomes:
measure: Global improvement in IBS symptoms as assessed by IBS Symptom Severity Scale (IBS-SSS)
timeFrame: 3 months.
measure: Global improvement in IBS symptoms as assessed by Birmingham Symptom scale questionnaire
timeFrame: 3 months.
measure: Quality of life as assessed by IBS quality of life (IBSQoL) questionnaire
timeFrame: 3 months
measure: Quality of life as assessed by Short form of Nepean Dyspepsia Index (SF-NDI) questionnaires
timeFrame: 3 months
measure: Fatigue as assessed by: Fatigue Assessment Scale (FAS) questionnaire
timeFrame: 3 months
Secondary outcomes:
measure: Stool microbiota changes as assessed by the Dysbiosis index (DI)
timeFrame: 3 months.
Other outcomes:
measure: Adverse events
timeFrame: up to the end point (3 months)
Locations:
city: Haugesund
country: Norway
facility: Helse Fonna
Study officials:
affiliation: Head of Research Department at Helse Finna HF
name: Haldis Lier, MD, PhD
role: STUDY_DIRECTOR
References:
citation: El-Salhy M, Winkel R, Casen C, Hausken T, Gilja OH, Hatlebakk JG. Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. Gastroenterology. 2022 Oct;163(4):982-994.e14. doi: 10.1053/j.gastro.2022.06.020. Epub 2022 Jun 14.
citation: El-Salhy M, Mazzawi T, Hausken T, Hatlebakk JG. The fecal microbiota transplantation response differs between patients with severe and moderate irritable bowel symptoms. Scand J Gastroenterol. 2022 Sep;57(9):1036-1045. doi: 10.1080/00365521.2022.2064725. Epub 2022 Apr 29.
citation: El-Salhy M, Mazzawi T, Hausken T, Hatlebakk JG. Irritable bowel syndrome patients who are not likely to respond to fecal microbiota transplantation. Neurogastroenterol Motil. 2022 Sep;34(9):e14353. doi: 10.1111/nmo.14353. Epub 2022 Mar 18.
citation: El-Salhy M, Kristoffersen AB, Valeur J, Casen C, Hatlebakk JG, Gilja OH, Hausken T. Long-term effects of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome. Neurogastroenterol Motil. 2022 Jan;34(1):e14200. doi: 10.1111/nmo.14200. Epub 2021 Jun 18.
citation: El-Salhy M, Valeur J, Hausken T, Gunnar Hatlebakk J. Changes in fecal short-chain fatty acids following fecal microbiota transplantation in patients with irritable bowel syndrome. Neurogastroenterol Motil. 2021 Feb;33(2):e13983. doi: 10.1111/nmo.13983. Epub 2020 Sep 17.
citation: El-Salhy M, Hatlebakk JG, Gilja OH, Brathen Kristoffersen A, Hausken T. Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut. 2020 May;69(5):859-867. doi: 10.1136/gutjnl-2019-319630. Epub 2019 Dec 18.