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

• Conditions: Crohn Disease; Inflammatory Bowel Diseases; Ulcerative Colitis

• Registration Number: NCT04079335
• Lead Sponsor: Chinese University of Hong Kong

Brief Summary

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

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.

Study Timeline

• Study Start: 2019-01-28
• Status Verified: 2019-09
• Study First Submitted: 2019-09-03
• Study First Submitted QC: 2019-09-03
• Last Update Submitted: 2019-09-03
• Study First Posted: 2019-09-06
• Last Update Posted: 2019-09-06
• Primary Completion: 2021-01-28
• Study Completion: 2021-01-28

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Patient with Crohn's Disease

1. Aged ≥18 years old
2. Confirmed diagnosis of ileo-colonic Crohn's disease according to established clinical, endoscopic and histologic criteria
3. History of at least one flare with symptoms that required intervention within 24 months before screening
4. Stable doses of immunosuppressive agents for at least 3 months if these agents are required
5. In clinical remission for at least 3 months, defined as Harvey Bradshaw Index (HBI) score < 4
6. Written informed consent obtained

Patient with Ulcerative Colitis

1. Aged ≥18 years old
2. Have a confirmed diagnosis of ulcerative colitis according to established clinical, endoscopic and histologic criteria
3. History of at least one flare with symptoms that required intervention within 24 months before screening
4. On stable regimen of 5-ASA for at least 3 months
5. In clinical remission for at least 3 months defined as partial Mayo score ≤ 1
6. Written informed consent obtained

Exclusion Criteria

1. Previous bowel surgery /stoma
2. On anti-TNF therapy
3. Malignant disease within 5 years
4. Use of probiotics, prebiotics or antibiotics in past 3 months
5. Terminal illness

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Trial Locations

Locations (1)

Chinese University of Hong Kong; 🇭🇰 Hong Kong, Hong Kong