FMT for Patients With IBS With Fecal and Mucosal Microbiota Assessment

• ClinicalTrials.gov Identifier: NCT03125564
• Recruitment Status: Recruiting
• First Posted: April 24, 2017
• Last Update Posted: July 18, 2018
• Sponsor: Chinese University of Hong Kong
• Information provided by (Responsible Party): Siew Chien NG, Chinese University of Hong Kong

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Irritable Bowel Syndrome; Fecal Microbiota Transplantation	Procedure: Fecal Microbiota Transplantation; Procedure: Sham; Procedure: Fecal and Mucosal Microbiota Assessment	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomised, Placebo-controlled Study on Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome With Fecal and Mucosal Microbiota Assessment
• Actual Study Start Date: April 12, 2017
• Estimated Primary Completion Date: January 2, 2019
• Estimated Study Completion Date: July 31, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fecal Microbiota Transplantation; FMT infusion and Fecal and Mucosal Microbiota Assessment	Procedure: Fecal Microbiota Transplantation; Fecal microbiota transplantation; Procedure: Fecal and Mucosal Microbiota Assessment; To assess the fecal and mucosal microbiota before and after Fecal Microbiota Transplantation
Sham Comparator: Sham infusion; Infusion with sham and Fecal and Mucosal Microbiota Assessment	Procedure: Sham; Infusion of sham; Procedure: Fecal and Mucosal Microbiota Assessment; To assess the fecal and mucosal microbiota before and after Fecal Microbiota Transplantation

Outcome Measures

Primary Outcome Measures :

1. The proportion of responder [ Time Frame: 12 weeks ]
   Record 1) worst abdominal pain and 2)stool consistency everyday

Secondary Outcome Measures :

1. The proportion of patients who had adequate relief of global IBS symptoms [ Time Frame: 12 weeks ]
   Adequate relief of global IBS symptoms
2. Assess the onset and duration of relief of IBS symptoms [ Time Frame: 12 weeks ]
   The onset and duration of relief of IBS symptoms
3. The proportion of patients who had improvement on worst abdominal bloating [ Time Frame: 12 weeks ]
   Proportion of patients who had improvement on worst abdominal bloating between the treatment arms.
4. Assess the onset and duration of worst abdominal bloating [ Time Frame: 12 weeks ]
   The onset and duration of worst abdominal bloating assessed by phone interview and on follow up visits.
5. The proportion of patients who had improvement of abdominal discomfort [ Time Frame: 12 weeks ]
   compare the difference in proportion of patients who had improvement on abdominal discomfort between the treatment arms.
6. Assess the onset and duration of abdominal discomfort [ Time Frame: 12 weeks ]
   The onset and duration of abdominal discomfort will be assessed through patient diary.
7. IBS-d global symptoms score [ Time Frame: 12 weeks ]
   The proportion of patients who had improvement on IBS-d global symptoms score

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 two 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

Contacts and Locations

Contacts

Contact: Amy Li; +852 26373225; amyli@cuhk.edu.hk

Contact: Whitney Tang; +852 35051519; whitneytang@cuhk.edu.hk

Locations

Hong Kong

The Chinese University of Hong Kong; Recruiting

Sha Tin, Hong Kong, 000000

Contact: Siew Chien Ng, PhD 35053996 siewchienng@cuhk.edu.hk

Sponsors and Collaborators

Chinese University of Hong Kong

Investigators

• Principal Investigator: Siew Ng, Prof.; Chinese University of Hong Kong

More Information

Publications:

Wilson S, Roberts L, Roalfe A, Bridge P, Singh S. Prevalence of irritable bowel syndrome: a community survey. Br J Gen Pract. 2004 Jul;54(504):495-502.

Talley NJ, Spiller R. Irritable bowel syndrome: a little understood organic bowel disease? Lancet. 2002 Aug 17;360(9332):555-64. Review.

Collins SM. A role for the gut microbiota in IBS. Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):497-505. doi: 10.1038/nrgastro.2014.40. Epub 2014 Apr 22. Review.

Kassinen A, Krogius-Kurikka L, Mäkivuokko H, Rinttilä 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. Epub 2007 Apr 14.

Ng SC, Lam EF, Lam TT, Chan Y, Law W, Tse PC, Kamm MA, Sung JJ, Chan FK, Wu JC. Effect of probiotic bacteria on the intestinal microbiota in irritable bowel syndrome. J Gastroenterol Hepatol. 2013 Oct;28(10):1624-31. doi: 10.1111/jgh.12306.

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.

Spiller R, Campbell E. Post-infectious irritable bowel syndrome. Curr Opin Gastroenterol. 2006 Jan;22(1):13-7. Review.

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. Review.

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.

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.

• Responsible Party: Siew Chien NG, Professor, Chinese University of Hong Kong
• ClinicalTrials.gov Identifier: NCT03125564 History of Changes
• Other Study ID Numbers: FMT-IBS study
• First Posted: April 24, 2017
• Last Update Posted: July 18, 2018
• Last Verified: July 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Irritable Bowel Syndrome; Syndrome; Disease; Pathologic Processes; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases