Clinical trial NCT02299973: Fecal Microbiota Transplantation in Irritable Bowel Syndrome With Bloating
Official title: Fecal Microbiota Transplantation in Irritable Bowel Syndrome With Bloating: a Double Blind, Placebo Controlled Randomised Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Keywords: irritable bowel syndrome
fecal microbiota transplantation
bloating
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2014-11-24
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Intestinal microbiota dysbiosis is thought to play an important role in the complex pathophysiology of irritable bowel syndrome (IBS), especially in diarrhoea-predominant IBS and possibly in IBS with severe bloating. Fecal microbiota transplantation or FMT has been shown to be an effective means of correcting this imbalance in the gut microbiota, especially in patients with recurrent Clostridium difficile infections where it has become a preferred treatment strategy.

In a preliminary pilot study in 12 patients we found that FMT was a safe and accepted therapy in IBS patients. In 75% of patients an amelioration of IBS symptoms in general and abdominal bloating was seen three months after transplantation.

In this study the effects of FMT on patients with IBS without constipation and bloating will be investigated in a double blind, placebo controlled RCT.

Detailed description: Intestinal microbiota dysbiosis is thought to play an important role in the complex pathophysiology of irritable bowel syndrome (IBS), especially in diarrhoea-predominant IBS and possibly in IBS with severe bloating. Fecal microbiota transplantation or FMT has been shown to be an effective means of correcting this imbalance in the gut microbiota, especially in patients with recurrent Clostridium difficile infections where it has become a preferred treatment strategy.

In a preliminary pilot study in 12 patients we found that FMT was a safe and accepted therapy in IBS patients. In 75% of patients an amelioration of IBS symptoms in general and abdominal bloating was seen three months after transplantation.

In this study the effects of FMT on patients with IBS without constipation and bloating will be investigated in a double blind, placebo controlled RCT. Donors for this study will be recruited from a healthy donor pool who will donate stool after clearance of a strict inclusion protocol which will assess the presence of any infectious diseases. Stool will be frozen following the protocol described in Hamilton et al 2012. Patients will deliver a stool portion that will be frozen as well.

At time of FMT, patients will be randomised in a double blinded fashion to the treatment arm (healthy donor stool) or placebo arm (own stool). Transplantation will be preformed by means of a colonoscopy with deliverance in the right colon and ileum.

Following FMT patients will be followed clinically with questionnaires and regular visits to the clinic. Stool samples will be collected on a regular basis for microbiome analysis.

At the end of the study, patients from the placebo-group will be given the opportunity to be transplanted with healthy donor stool if necessary. Follow-up will continu for a total duration of one year.

Eligibility criteria: 1. Inclusion Criteria for patients:

   * signed informed consent
   * Irritable bowel syndrome with predominant diarrhoea as defined by the ROME III criteria and with symptoms of abdominal bloating
   * IBS symptom score \> 3 on at least 2 subscores (abdominal discomfort, abdominal bloating, abdominal pain, urgency, stool frequency, stool consistency)
2. Exclusion Criteria for patients:

   * predominant constipation as defined by Rome III criteria
   * pregnancy or inadequate anti conception for the duration of the trial
   * celiac disease
   * any contra-indications for colonoscopy
   * structural abnormalities of the colon (e.g. ileocecal resection, gastric bypass)
   * severe gastro-intestinal comorbidities (e.g. IBD, coloncarcinoma)
   * non gastro-intestinal malignancy
   * severe psychiatric comorbidity which had important effects on the quality of life
   * antimicrobial treatment 4 weeks prior to screening visit
   * treatment with probiotics 2 weeks prior to screening visit
   * recent diagnosis of lactose intolerance (\< 3 months before screening visit)
   * any severe comorbidity that might interfere with the study course as determined by the treating physician
3. Inclusion criteria for donors

   * age 18 - 75 years
   * signed informed consent
   * normal screening protocol which includes screening for infectious diseases (eg. blood HIV, Syphilis, Hepatitis B or C; stool: enteropathogens, clostridium, ESBL, CPE)
4. Exclusion criteria for donors

   * presence of gastrointestinal symptoms
   * gastro-intestinal or other important comorbidity
   * obesity or metabolic syndrome
   * history of malignancy both gastrointestinal or systemic
   * presence of known colon polyps
   * recent placing of piercings/tattoos
   * sexual risk behaviour
   * antimicrobial therapy 3 months prior to donation

Primary outcomes:
measure: Reduction of overall IBS symptoms (Key question 1)
timeFrame: 3 months after FMT
measure: Reduction of abdominal bloating (Key question 2)
timeFrame: 3 months after FMT
Secondary outcomes:
measure: Changes in fecal microbiome composition (Illumina sequencing)
timeFrame: 3 months after FMT
measure: Changes in IBS symptom scores at three months after FMT
timeFrame: 3 months after FMT
measure: Changes in IBS symptom scores at six months post FMT
timeFrame: 6 months
measure: Changes in IBS symtom scores at 9 months post FMT
timeFrame: 9 months
measure: Changes in IBS symptom scores at 1 year post FMT
timeFrame: 1 year
measure: Composition of mucosal-adherent microbiota (Illumina sequencing)
timeFrame: 3 months
measure: Changes of IBS symptom scores in patients who undergo an off-trial FMT
timeFrame: 3 months
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Ghent University Hospital
Study officials:
affiliation: University Hospital, Ghent
name: Danny De Looze, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dupont HL. Review article: evidence for the role of gut microbiota in irritable bowel syndrome and its potential influence on therapeutic targets. Aliment Pharmacol Ther. 2014 May;39(10):1033-42. doi: 10.1111/apt.12728. Epub 2014 Mar 25.
citation: Kassinen A, Krogius-Kurikka L, Makivuokko H, Rinttila T, Paulin L, Corander J, Malinen E, Apajalahti J, Palva A. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology. 2007 Jul;133(1):24-33. doi: 10.1053/j.gastro.2007.04.005. Epub 2007 Apr 14.
citation: van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15. doi: 10.1056/NEJMoa1205037. Epub 2013 Jan 16.
citation: Borody TJ, Paramsothy S, Agrawal G. Fecal microbiota transplantation: indications, methods, evidence, and future directions. Curr Gastroenterol Rep. 2013 Aug;15(8):337. doi: 10.1007/s11894-013-0337-1.
citation: Holvoet T, Joossens M, Vazquez-Castellanos JF, Christiaens E, Heyerick L, Boelens J, Verhasselt B, van Vlierberghe H, De Vos M, Raes J, De Looze D. Fecal Microbiota Transplantation Reduces Symptoms in Some Patients With Irritable Bowel Syndrome With Predominant Abdominal Bloating: Short- and Long-term Results From a Placebo-Controlled Randomized Trial. Gastroenterology. 2021 Jan;160(1):145-157.e8. doi: 10.1053/j.gastro.2020.07.013. Epub 2020 Jul 15.