Clinical trial NCT05598489: Development of Novel Fecal Microbial Biomarkers for Inflammatory Bowel Disease
Official title: Development of Novel Fecal Microbial Biomarkers for Inflammatory Bowel Disease
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Inflammatory Bowel Diseases
Ulcerative Colitis
Crohn Disease
Microbiome
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
Collaborators: name: National Taiwan University
name: Hanoi Medical University
name: Mahidol University
name: Indonesia University
name: National University of Malaysia
name: Kiang Wu Hospital
name: National Academy of Medical Sciences, Nepal
name: Duke-NUS Graduate Medical School
name: National University Hospital, Singapore
name: Heidelberg University
name: University of Chicago
name: Ruijin Hospital
First posted: 2022-10-28
Enrollment: 3300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Cases (Crohn's disease or Ulcerative colitis) and healthy controls

Brief summary: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative colitis (UC), is a chronic idiopathic inflammatory condition of the intestine. Endoscopy has been used to monitor the 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 to monitor disease including C-reactive protein and stool leucocyte markers including fecal calprotectin, but their sensitivity and specificity in correlating to intestinal inflammation activity are low. Clinical challenge of patient heterogeneity in disease phenotype and response to therapy has compounded discovery of disease-related biomarkers. 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. Moreover, overall bacterial diversity is consistently decreased in IBD patients compared to controls. Even though a number of fecal biomarkers have been evaluated for their utility for disease diagnosis in IBD, to date none has been accurate enough for clinical application. Therefore, identification and validation of a non-invasive biomarker which can be easily applied in disease diagnosis and prognosis is warranted to provide an earlier opportunity to intervene. In this study, it aims to develop a metagenomics-based model using fecal microbial biomarkers for differentiating IBD patients from healthy controls, and then validate these fecal microbial biomarkers in different populations.

Detailed description: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative colitis (UC), 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.

Endoscopy has been used to monitor the 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 to monitor disease including C-reactive protein and stool leucocyte markers including fecal calprotectin, but their sensitivity and specificity in correlating to intestinal inflammation activity are low. Clinical challenge of patient heterogeneity in disease phenotype and response to therapy has compounded discovery of disease-related biomarkers. 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. Moreover, overall bacterial diversity is consistently decreased in IBD patients compared to controls. Even though a number of fecal biomarkers have been evaluated for their utility for disease diagnosis in IBD, to date none has been accurate enough for clinical application. Therefore, identification and validation of a non-invasive biomarker which can be easily applied in disease diagnosis and prognosis is warranted to provide an earlier opportunity to intervene.

In this study, it aims to develop a metagenomics-based model using fecal microbial biomarkers for differentiating IBD patients from healthy controls, and then validate these fecal microbial biomarkers in different populations.

This is a cross-sectional multi-centre study. Two groups of subjects, IBD patients (cases) and healthy subjects (controls), will be recruited from each centre. Each center will provide fecal samples from 80-100 Crohn's disease, 80-100 ulcerative colitis, and 80-100 controls. We will collect clinical data and stool sample from each subject. Fecal microbiota composition will be compared between cases and controls. The abundance of bacterial biomarkers will be assessed, and the efficacy of a diagnostic model will be validated.

Eligibility criteria: Cases (Crohn's disease or Ulcerative colitis)

Inclusion Criteria:

* Aged ≥18 years old
* Confirmed diagnosis of Crohn's disease or Ulcerative colitis defined by endoscopy, radiology, and histology
* Competent to provide informed consent

Exclusion Criteria:

* Use of antibiotics in the last 1 month
* Known current sepsis (excluding uncomplicated infections such as influenza)
* Known history of severe organ failure (including decompensated cirrhosis, malignant disease, kidney failure, epilepsy, active serious infection, acquired immunodeficiency syndrome)
* Major bowel surgery in the last 6 months (excluding colonoscopy/ procedure related to perianal disease)
* Presence of an ileostomy / stoma
* Current pregnancy

Controls Inclusion Criteria

* Aged ≥18 years old
* No known medical history including inflammatory bowel disease, irritable bowel syndrome or GI malignancy
* Competent to provide informed consent

Exclusion Criteria

* Use of antibiotics in the last 1 month
* Known current sepsis (excluding uncomplicated infections such as influenza)
* Known history of severe organ failure (including decompensated cirrhosis, malignant disease, kidney failure, epilepsy, active serious infection, acquired immunodeficiency syndrome)
* Bowel surgery in the last 6 months (excluding colonoscopy/ procedure related to perianal disease)
* Presence of an ileos

Primary outcomes:
measure: Fecal microbial biomarkers for IBD
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
Study officials:
affiliation: Chinese University of Hong Kong
name: Siew Chien Ng, PhD
role: PRINCIPAL_INVESTIGATOR
References: