A Prospective Longitudinal Study of Fecal Microbiome and Calprotectin to Predict Relapse in Patients With IBD

Study Overview
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Brief Summary
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Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory condition of the intestine, which results in diarrhea, rectal bleeding, urgency, weight loss and abdominal pain. The natural course of IBD is characterized by activity outbreaks and periods of remission. In most cases, relapses in Crohn's disease (CD) and in ulcerative colitis (UC) are unpredictable and despite effective medical treatment, a degree of subclinical inflammation may persist in the bowel wall, contributing to a significant risk of relapse. In IBD, altered fecal microbiota signatures have been consistently reported which included a reduction in biodiversity with lower proportions of Firmicutes and increases in Proteobacteria and Bacteroidetes phylum members. It is however unclear whether changes in microbial profile including diversity and composition can predict disease relapse in IBD. We hypothesize that fecal microbial signatures in conjunction with fecal calprotectin may play a role in predicting relapse in IBD patients.

Detailed Description
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Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory condition of the intestine, which results in diarrhea, rectal bleeding, urgency, weight loss and abdominal pain. The natural course of IBD is characterized by activity outbreaks and periods of remission. In most cases, relapses in Crohn's disease (CD) and in ulcerative colitis (UC) are unpredictable and despite effective medical treatment, a degree of subclinical inflammation may persist in the bowel wall, contributing to a significant risk of relapse. Endoscopy has been used to monitor a disease but it is time-consuming, costly, invasive, and associated with certain risks of morbidity. Many patients are reluctant to undergo repeated endoscopic examinations, particularly when their disease is quiescent. Acute phase reactants have been used but their sensitivity and specificity in correlating to intestinal inflammatory activity are very low, and their capacity to predict disease relapse is poor and controversial. A number of fecal biomarkers have been evaluated for their utility for monitoring and predicting relapse in IBD but some of these biomarkers are also not specific. In IBD, altered fecal microbiota signatures have been consistently reported which included a reduction in biodiversity with lower proportions of Firmicutes and increases in Proteobacteria and Bacteroidetes phylum members. In addition, disease remission and relapse are associated with microbial changes in both mucosal and fecal samples. In particular, a loss of species richness in Crohn's disease has been widely observed. Recently microbial biomarkers may differentiate between CD and UC. Furthermore, different microbial groups are associated with smoking habit and localization of the disease in CD and UC. It is however unclear whether changes in microbial profile including diversity and composition can predict disease relapse in IBD. We hypothesize that fecal microbial signatures in conjunction with fecal calprotectin may play a role in predicting relapse in IBD patients.

Official Title
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A Prospective Longitudinal Study of Fecal Microbiome and Calprotectin to Predict Relapse in Patients With Inflammatory Bowel Disease

Conditions
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Inflammatory Bowel Diseases, Ulcerative Colitis, Crohn Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with Crohn's Disease Aged ≥18 years old Confirmed diagnosis of ileo-colonic Crohn's disease according to established clinical, endoscopic and histologic criteria History of at least one flare with symptoms that required intervention within 24 months before screening Stable doses of immunosuppressive agents for at least 3 months if these agents are required In clinical remission for at least 3 months, defined as Harvey Bradshaw Index (HBI) score < 4 Written informed consent obtained Patient with Ulcerative Colitis Aged ≥18 years old Have a confirmed diagnosis of ulcerative colitis according to established clinical, endoscopic and histologic criteria History of at least one flare with symptoms that required intervention within 24 months before screening On stable regimen of 5-ASA for at least 3 months In clinical remission for at least 3 months defined as partial Mayo score ≤ 1 Written informed consent obtained Exclusion Criteria: Previous bowel surgery /stoma On anti-TNF therapy Malignant disease within 5 years Use of probiotics, prebiotics or antibiotics in past 3 months Terminal illness

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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical relapse for CD patients | Defined as worsening of the symptoms, accompanied by HBI score of ≥ 8 points for CD and require a change in therapy. | 2 years | 
| Clinical relapse for UC patients | Defined as partial Mayo score of ≥ 5 points for UC and require a change in therapy. | 2 years |