FMT for Patients With IBS With Fecal and Mucosal Microbiota Assessment

Not Applicable

Completed

• Conditions: Fecal Microbiota Transplantation; Irritable Bowel Syndrome
• Interventions: Procedure: Sham; Procedure: Fecal Microbiota Transplantation; Procedure: Fecal and Mucosal Microbiota Assessment

• Registration Number: NCT03125564
• Lead Sponsor: Chinese University of Hong Kong

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.

Study Timeline

• Study First Submitted: 2017-04-07
• Study Start: 2017-04-12
• Study First Submitted QC: 2017-04-19
• Study First Posted: 2017-04-24
• Primary Completion: 2022-09-16
• Study Completion: 2023-12-16
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-21
• Last Update Posted: 2024-08-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham infusion	Sham	Infusion with sham and Fecal and Mucosal Microbiota Assessment
Sham infusion	Fecal and Mucosal Microbiota Assessment	Infusion with sham and Fecal and Mucosal Microbiota Assessment
Fecal Microbiota Transplantation	Fecal Microbiota Transplantation	FMT infusion and Fecal and Mucosal Microbiota Assessment
Fecal Microbiota Transplantation	Fecal and Mucosal Microbiota Assessment	FMT infusion and Fecal and Mucosal Microbiota Assessment

Primary Outcome Measures

Name	Time	Method
the proportion of responders	12 weeks	Response means a symptom relief of more than 50 points assessed by IBS-SSS.

Secondary Outcome Measures

Name	Time	Method
Assess the change of abdominal pain scores in patients who undergo open-label FMT	12 weeks	After unblinding, patients in the placebo group will be given a choice to receive open-label FMT and follow up under the same schedule as the blinded phase. The abdominal pain scores will be assessed by symptoms diary on a scale of 0-10 and higher scores mean severe abdominal pain
The proportion of patients who had improvement on abdominal bloating	12 weeks	Proportion of patients who had improvement on abdominal bloating between the treatment arms.
Assess the Stool consistency between two groups	12 weeks	Assess stool consistency by Bristol Stool Scale between treatment and placebo arms. The Bristol Stool Scale ranges from 1 to 7.
Health-related quality of life in patients with irritable bowel syndrome	12 weeks	Assess quality of life by Irritable Bowel Syndrome Quality of Life (IBS-QOL) scale between treatment and placebo arms. The IBS-QOL scale ranges from 0 to 100 scores with higher scores indicating better quality of life.
Assess the onset and duration of relief of general IBS symptoms	12 weeks	The onset and duration of relief of general IBS symptoms
The similarity of gut microbiota to donors	12 weeks	Assessing the similarity of gut microbiota to donors in patients following FMT
Assess the onset and duration of abdominal bloating relief	12 weeks	The onset and duration of abdominal bloating relief were assessed by phone interview and follow-up visits.
Assess the Abdominal pain between two groups	12 weeks	Assess abdominal pain by symptoms diary between treatment and placebo arms. The symptoms diary assesses abdominal pain on a scale of 0-10 and higher scores mean severe abdominal pain
Assess the level of anxiety between two groups	12 weeks	Assess the Anxiety scale by General Anxiety Disorder-7 (GAD-7) between treatment and placebo arms. The total scores of GAD-7 range from 0 to 21 with higher scores indicating more severe level of anxiety.
The proportion of patients who undergo open-label FMT and have abdominal bloating relief	12 weeks	After unblinding, patients in the placebo group will be given a choice to receive open-label FMT and follow up under the same schedule as the blinded phase. The abdominal bloating relief was assessed by phone interview and follow-up visits.
The IBS quality of life change in patients who undergo open-label FMT	12 weeks	After unblinding, patients in the placebo group will be given a choice to receive open-label FMT and follow up under the same schedule as the blinded phase. Quality of life was assessed by Irritable Bowel Syndrome Quality of Life (IBS-QOL) scale which ranges from 0 to 100 scores with higher scores indicating better quality of life.
The changes in gut microbiota at species and functional levels	12 weeks	Assessing changes in gut microbiota at species and functional levels in patients receiving FMT or placebo
The proportion of patients who had adequate relief of general IBS symptoms	12 weeks	Adequate relief of general IBS symptoms
The level of anxiety change in patients who undergo open-label FMT	12 weeks	After unblinding, patients in the placebo group will be given a choice to receive open-label FMT and follow up under the same schedule as the blinded phase. Anxiety was assessed by General Anxiety Disorder-7 (GAD-7). The total scores of GAD-7 range from 0 to 21 with higher scores indicating more severe level of anxiety.
The changes in diversity and richness of gut microbiota	12 weeks	Evaluating the changes in the diversity (shannon index) and richness (number of observed species) of gut microbiota of patients receiving FMT or placebo

Trial Locations

Locations (1)

The Chinese University of Hong Kong; 🇭🇰 Sha Tin, Hong Kong