FMT for Patients With IBS With Fecal and Mucosal Microbiota Assessment

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomised, Placebo-controlled Study on Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome With Fecal and Mucosal Microbiota Assessment

Conditions
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Irritable Bowel Syndrome, Fecal Microbiota Transplantation

Intervention / Treatment
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* Procedure: Fecal Microbiota Transplantation
* Procedure: Sham
* Procedure: Fecal and Mucosal Microbiota Assessment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fecal Microbiota Transplantation<br>FMT infusion and Fecal and Mucosal Microbiota Assessment | Procedure: Fecal Microbiota Transplantation<br>* Fecal microbiota transplantation<br>Procedure: Fecal and Mucosal Microbiota Assessment<br>* To assess the fecal and mucosal microbiota before and after Fecal Microbiota Transplantation<br>|
| Sham Comparator: Sham infusion<br>Infusion with sham and Fecal and Mucosal Microbiota Assessment | Procedure: Sham<br>* Infusion of sham<br>Procedure: Fecal and Mucosal Microbiota Assessment<br>* To assess the fecal and mucosal microbiota before and after Fecal Microbiota Transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the proportion of responders | Response means a symptom relief of more than 50 points assessed by IBS-SSS. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients who had adequate relief of general IBS symptoms | Adequate relief of general IBS symptoms | 12 weeks | 
| Assess the onset and duration of relief of general IBS symptoms | The onset and duration of relief of general IBS symptoms | 12 weeks | 
| The proportion of patients who had improvement on abdominal bloating | Proportion of patients who had improvement on abdominal bloating between the treatment arms. | 12 weeks | 
| Assess the onset and duration of abdominal bloating relief | The onset and duration of abdominal bloating relief were assessed by phone interview and follow-up visits. | 12 weeks | 
| Assess the Abdominal pain between two groups | 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 | 12 weeks | 
| Assess the Stool consistency between two groups | Assess stool consistency by Bristol Stool Scale between treatment and placebo arms. The Bristol Stool Scale ranges from 1 to 7. | 12 weeks | 
| Health-related quality of life in patients with irritable bowel syndrome | 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. | 12 weeks | 
| Assess the level of anxiety between two groups | 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. | 12 weeks | 
| Assess the change of abdominal pain scores in patients who undergo open-label FMT | 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 | 12 weeks | 
| The proportion of patients who undergo open-label FMT and have abdominal bloating relief | 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. | 12 weeks | 
| The IBS quality of life change in patients who undergo open-label FMT | 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. | 12 weeks | 
| The level of anxiety change in patients who undergo open-label FMT | 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. | 12 weeks | 
| The changes in diversity and richness of gut microbiota | Evaluating the changes in the diversity (shannon index) and richness (number of observed species) of gut microbiota of patients receiving FMT or placebo | 12 weeks | 
| The changes in gut microbiota at species and functional levels | Assessing changes in gut microbiota at species and functional levels in patients receiving FMT or placebo | 12 weeks | 
| The similarity of gut microbiota to donors | Assessing the similarity of gut microbiota to donors in patients following FMT | 12 weeks |