Clinical trial NCT03125564: FMT for Patients With IBS With Fecal and Mucosal Microbiota Assessment
Official title: A Randomised, Placebo-controlled Study on Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome With Fecal and Mucosal Microbiota Assessment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Fecal Microbiota Transplantation
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2017-04-24
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Irritable bowel syndrome (IBS) is a common functional bowel disorder of the gastrointestinal tract affecting up to 20 percent of the adolescent and adult populations. It is characterised by abdominal pain, irregular bowel habits, altered stool consistencies and bloating, and is associated with impaired quality of life. IBS can be categorised into diarrhoea predominant type (IBS-D), constipation predominant type (IBS-C), and mixed type (IBS-M). Fecal microbiota transplantation (FMT) defined as infusion of feces from healthy donors to affected subjects has shown impressive results with high cure rates in patients with recurrent clostridium difficile infections. The investigators propose a randomised, placebo-controlled trial of FMT in patients with IBS.

Detailed description: Irritable bowel syndrome (IBS) is a common functional bowel disorder of the gastrointestinal tract affecting up to 20 percent of the adolescent and adult populations. It is characterised by abdominal pain, irregular bowel habits, altered stool consistencies and bloating, and is associated with impaired quality of life. IBS can be categorised into diarrhoea predominant type (IBS-D), constipation predominant type (IBS-C), and mixed type (IBS-M). Until recently, the development of an effective therapy for this condition has been hampered by a poor understanding of the etiology of the disease. Traditionally the underlying pathogenesis of IBS has been centered on the brain-gut axis whereby stress and psychological conditions alter the perception of IBS symptoms. Emerging evidence however supports the observation that at least in a subgroup of patients with IBS, peripheral mechanisms within the intestine including low grade mucosal inflammation, abnormal immune activation and altered visceral sensitivity may be the main drivers of the manifestations in IBS.

Accumulating data suggest that the intestinal microbiota play an important role in the pathophysiology of IBS. This is derived from early observation that post-infectious IBS developed in a subgroup of patients following a bout of gastroenteritis. Several studies have shown that the fecal microbiota was altered in IBS and IBS symptoms can be improved by therapeutic interventions that target the microbiota including antibiotics, probiotics and prebiotics. Rifaximin, an oral, non-systemic broad spectrum antibiotics has also been shown to provide significant relief in IBS symptoms in a randomized controlled trial.

Fecal microbiota transplantation (FMT) defined as infusion of feces from healthy donors to affected subjects has shown impressive results with high cure rates in patients with recurrent clostridium difficile infections.The mechanism of FMT in IBS is not completely clear.

The investigators propose a randomised, placebo-controlled trial of FMT in patients with IBS.

Eligibility criteria: Inclusion Criteria:

* Patients are aged 18 or above
* Patients have a diagnosis of IBS consistent with the Rome III criteria (13)
* Patients did not have adequate relief of global IBS symptoms and of IBS-related bloating at both the time of screening and the time of randomization
* Patients had undergone clinical investigations with colonoscopy within five years of recruitment
* Patients with written informed consent form provided

Exclusion Criteria:

* Patients have constipation predominant IBS (according to the definition of Rome III criteria)
* Patients have a history of inflammatory bowel disease or gastrointestinal malignancy
* Patients have previous abdominal surgery (other than cholecystectomy or appendectomy)
* Patients have human immunodeficiency virus infection
* Patients have renal disease manifested by 1.5 times the ULN of serum creatinine or blood urea nitrogen level
* Patients have hepatic disease manifested by twice the upper limit of normal (ULN) for any of the following liver function tests: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or total bilirubin (except in isolated elevation of unconjugated bilirubin
* Patients have diabetes mellitus manifested by HbA1C \> 6.5%
* Patients have abnormal thyroid function manifested by values of serum Sensitive Thyroid Stimulating Hormone and serum free T4 fall outside the reference range which is not controlled by thyroid medications
* Patients have a history of psychiatric illness (mania and schizophrenia)
* Patients have depression defined by having a Patient Health Questionnaire-9 (PHQ-9) score \> 15
* Patients have anxiety defined by having a Generalized Anxiety Disorder 7 (GAD7) score \> 10
* Patients have active infection at the time of inclusion
* Patients have used antibiotic therapy or anti-inflammatory drugs within the past 7 days
* Patients have any other organic causes that can explain the symptoms of IBS
* Current pregnancy

Primary outcomes:
measure: the proportion of responders
timeFrame: 12 weeks
Secondary outcomes:
measure: The proportion of patients who had adequate relief of general IBS symptoms
timeFrame: 12 weeks
measure: Assess the onset and duration of relief of general IBS symptoms
timeFrame: 12 weeks
measure: The proportion of patients who had improvement on abdominal bloating
timeFrame: 12 weeks
measure: Assess the onset and duration of abdominal bloating relief
timeFrame: 12 weeks
measure: Assess the Abdominal pain between two groups
timeFrame: 12 weeks
measure: Assess the Stool consistency between two groups
timeFrame: 12 weeks
measure: Health-related quality of life in patients with irritable bowel syndrome
timeFrame: 12 weeks
measure: Assess the level of anxiety between two groups
timeFrame: 12 weeks
measure: Assess the change of abdominal pain scores in patients who undergo open-label FMT
timeFrame: 12 weeks
measure: The proportion of patients who undergo open-label FMT and have abdominal bloating relief
timeFrame: 12 weeks
measure: The IBS quality of life change in patients who undergo open-label FMT
timeFrame: 12 weeks
measure: The level of anxiety change in patients who undergo open-label FMT
timeFrame: 12 weeks
measure: The changes in diversity and richness of gut microbiota
timeFrame: 12 weeks
measure: The changes in gut microbiota at species and functional levels
timeFrame: 12 weeks
measure: The similarity of gut microbiota to donors
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Sha Tin
country: Hong Kong
facility: The Chinese University of Hong Kong
Study officials:
affiliation: Chinese University of Hong Kong
name: Siew Ng, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Gwee KA, Graham JC, McKendrick MW, Collins SM, Marshall JS, Walters SJ, Read NW. Psychometric scores and persistence of irritable bowel after infectious diarrhoea. Lancet. 1996 Jan 20;347(8995):150-3. doi: 10.1016/s0140-6736(96)90341-4.
citation: Spiller R, Campbell E. Post-infectious irritable bowel syndrome. Curr Opin Gastroenterol. 2006 Jan;22(1):13-7. doi: 10.1097/01.mog.0000194792.36466.5c.
citation: Parkes GC, Sanderson JD, Whelan K. Treating irritable bowel syndrome with probiotics: the evidence. Proc Nutr Soc. 2010 May;69(2):187-94. doi: 10.1017/S002966511000011X. Epub 2010 Mar 18.
citation: Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP; TARGET Study Group. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011 Jan 6;364(1):22-32. doi: 10.1056/NEJMoa1004409.
citation: van Nood E, Dijkgraaf MG, Keller JJ. Duodenal infusion of feces for recurrent Clostridium difficile. N Engl J Med. 2013 May 30;368(22):2145. doi: 10.1056/NEJMc1303919. No abstract available.