Predicting IBD Treatment Outcomes With Gut Microbiome Analysis

Crohn Disease Clinical Trial

— OPTIMIST  

Official title:

Optimizing Patient Treatment Involving Microbiome Integration for Specialized Therapeutics

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06453720
• Other study ID #: H23-02927
• Status: Not yet recruiting
• Start date: June 7, 2024
• Est. completion date: December 7, 2025

Study information

• Verified date: June 2024
• Source: University of British Columbia
• Contact: Fanny LeMarié, PhD
• Phone: 6044414992
• Email: flemarie[@]ibdcentrebc.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this prospective observational study is to determine if specific microbiome signatures can predict therapeutic responses in adult patients with Crohn's disease (CD), a form of inflammatory bowel disease (IBD), living in British Columbia, Canada. The main questions this study seeks to answer are:

1. Can microbiome signatures across different sample types (fecal, intestinal washings, and intestinal epithelial biopsies) predict response to therapy in CD?

2. How do microbiome profiles differ between active and quiescent CD and non-IBD controls?

Researchers will compare microbiome signatures in patients with active and inactive CD as well as non-IBD controls to see if there are any microbial signatures that predict response to therapy.

Participants will:

1. Provide fecal and blood samples.

2. Undergo intestinal washings and intestinal epithelial biopsy specimens taken during routine colonoscopy.

3. Participate in a longitudinal follow-up over 12 months to monitor clinical, biochemical, and endoscopic responses to therapy.

Description:

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory condition affecting the gastrointestinal (GI) tract. The study aims to evaluate microbiome profiles (bacteriome, and mycobiome) across three different sample types (fecal, intestinal washings, and intestinal epithelial biopsies) in a cohort of adult patients with Crohn's disease (CD) living in British Columbia, Canada, and investigate whether a microbial signature may predict response to IBD therapy.

Aims:

1. Determine microbiome signatures, across different sample types, in quiescent and active disease for patients with CD living in BC, Canada.

2. Evaluate whether fecal, mucosal, and/or intestinal epithelial biopsy microbiome signatures can predict response to therapy.

Methods

Study Design:

Phase 1: A cross-sectional pilot study to evaluate the microbiome in patients with IBD (with active and quiescent disease) and in non-IBD controls.

Primary Outcome: Compare results of microbial analyses (including bacteriome and mycobiome) across three different sample types: intestinal washings and intestinal epithelial biopsy specimens taken during colonoscopy, as well as fecal samples.

Secondary Outcomes: Investigate correlations between the microbial analyses across different sample types and disease activity in CD. Compare the difference in microbial analyses within each sample type between active and quiescent CD as well as non-IBD patients. Investigate if fecal microbiome composition and function 2 weeks after bowel preparation is comparable to pre-bowel preparation fecal microbiome in a subset of patients with CD.

Phase 2: A longitudinal observational study with a 12-month follow-up.

Primary Outcome: Identify if there are any microbial signatures that predict response to therapy in patients with active disease requiring escalated therapy, assessed clinically and biochemically after induction (12-16 weeks) and at 12 months (+/- 3 months).

Secondary Outcomes: Compare the sensitivity and specificity of microbial analyses from each sample type in predicting response to therapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 7, 2025
• Est. primary completion date: December 7, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 80 Years

Eligibility

Inclusion Criteria:

CD patients

• Adult patients =19 years old and = 80 years old.

• CD with distal small bowel and/or colonic involvement that is endoscopically assessable with colonoscopy

• Undergoing colonoscopy as part of routine clinical care

• Active or quiescent disease

• Active disease will be defined as a simple endoscopic score for CD (SES-CD) =7 or =4 for isolated ileal CD and at least one large ulcer (=5mm)

• Quiescent disease is defined as an SES-CD <3.

Non-IBD controls

• Adult patients = 19 years old and = 80 years old.

• Undergoing colonoscopy as part of colorectal screening

Exclusion Criteria:

CD patients

• Active perianal CD - defined as collection on MRI or clinically active fistula (i.e., draining fistula)

• Proximal small bowel (defined as not endoscopically assessable by colonoscopy) or isolated upper GI CD

• Antibiotics in the last 3 months for any indication

• Prebiotic, probiotic or postbiotic supplements in the last month

• Gastroenteritis or travel outside of Canada and the United States in the last month

• Colorectal cancer, high-grade dysplasia or a polyp =2cm diagnosed at baseline endoscopy

• Pregnant or breastfeeding

• Bowel resection within the preceding 4 months

• Primary sclerosing cholangitis

Non-IBD controls

• Found to have inflammation (deemed by endoscopist) at colonoscopy.

• History of IBD in 1st degree relative.

• Antibiotics in the last 3 months.

• Prebiotic, probiotic or postbiotic supplements in the last month.

• Gastroenteritis or travel outside of Canada and the United States in the last month.

• Pregnant or breastfeeding.

• Previous bowel surgeries.

Related Conditions & MeSH terms

• Crohn Disease
• Inflammatory Bowel Diseases

Intervention

Procedure:
• Colonoscopy
A colonoscopy will be performed as part of routine clinical care for all participants, with the study not requiring any additional scheduling commitments outside of routine care.

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
University of British Columbia	GI Research Institute, IBD Centre of BC, Pacific Gastroenterology Associates

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare results of microbial analyses (including bacteriome and mycobiome) across three different sample types: intestinal washings and intestinal epithelial biopsy specimens taken during colonoscopy as well as fecal samples.	Microbial analyses that will be undertaken for each sample type are as follows: Stool: Metagenomics (Shotgun sequencing, ITS sequencing for fungal analysis); Metaproteomics and metabolomics (Host, microbial, and dietary protein analysis, microbial metabolite analysis); Anaerobic culturing (Simulate gut environment, use dietary substrates to target key microbes); Biopsy specimens: Organoid culturing (In vitro gut model analysis, epithelial-microbiome analysis, mucin production analysis); RNA-seq, transcriptomics (Gene expression profiling analysis, disease marker identification); Metagenomics; Metaproteomics and metabolomics; Intestinal washings: Mucin analysis (Glycoprotein analysis); Metagenomics; Metaproteomics and metabolomics	24 months
Primary	In patients with active Crohn's disease, where a decision is made to escalate therapy after the index endoscopy, identify if there are any microbial signatures that predict response to therapy after induction (12 - 16 weeks).	Clinical Response: Defined based on changes in clinical symptoms as per standardized clinical scoring systems (SES-CD).; Biochemical Response: Assessed through C-reactive protein (CRP) levels and fecal calprotectin, two biomarkers that indicate inflammation or disease activity.; The Simple Endoscopy Score for Crohn's Disease (SES-CD) is an objective clinical assessment of the severity of a patient's Crohn's disease. A higher score means more severe disease activity. The three severity classes of SES-CD scoring are as follows: Endoscopic remission (SES-CD <3).; Moderate to severe endoscopically active disease (SES-CD =7 or =4 for isolated ileal CD and at least one large ulcer (=5mm)).; Mild endoscopically active disease (SES-CD of 3-6, or 3 with isolated ileal CD, with no large ulcers).	24 months
Primary	In patients with active Crohn's disease, where a decision is made to escalate therapy after the index endoscopy, identify if there are any microbial signatures that predict sustained response to therapy at 12 Months (+/- 3 months).	Clinical Response: Continuation or improvement in clinical symptoms as measured by standardized clinical scoring systems (SES-CD).; Biochemical Response: Persistent normalization or improvement in CRP levels and fecal calprotectin.; Endoscopic Response: Improvement or healing of mucosal lesions as observed during endoscopic examination, assessed by validated clinical scoring systems (SES-CD).	24 months
Secondary	Investigate the correlations between the microbial analyses across different sample types and disease activity in CD.	Correlation Analysis: Statistical measures will be used to assess the strength and direction of the relationship between microbial composition in different sample types (intestine washings, intestinal biopsy, fecal samples) and disease activity in CD.; Disease Activity Measures: Disease activity will be assessed using the modified Harvey-Bradshaw Index, biochemical markers (CRP, fecal calprotectin), and endoscopic findings (SES-CD).	24 months
Secondary	Compare the difference in microbial analyses within each sample type between active and quiescent CD as well as non-IBD patients.	Assessments: 1. Microbial Diversity Metrics: Alpha-diversity Metrics: Shannon index; Inverse Simpson diversity index; Chao1; These metrics will be used to compare microbial diversity within each sample type between active and quiescent CD patients, as well as non-IBD patients.	24 months
Secondary	Compare the difference in microbial analyses within each sample type between active and quiescent CD as well as non-IBD patients.	Assessments: Differential Abundance Analysis: Differential abundance analysis will be performed using generalized linear models to identify specific microbial taxa that are significantly different between active and quiescent CD patients, and non-IBD patients within each sample type.	24 months
Secondary	Investigate, in a subset of patients with CD, if fecal microbiome composition and function 2 weeks after bowel preparation is comparable to pre-bowel preparation fecal microbiome.	Assessments: Comparison of Microbial Composition: Beta-diversity metrics (Bray-Curtis dissimilarity, Jaccard index) and phylogenetic-dependent distance metrics (weighted and unweighted UniFrac) will be calculated, and subsequent clustering will be applied using a principal coordinate analysis (PCoA). To test for overall microbiome differences, a PERMANOVA test will be applied. The Benjamini-Hochberg method will be applied to control for the false discovery rate.	24 months
Secondary	Investigate, in a subset of patients with CD, if fecal microbiome composition and function 2 weeks after bowel preparation is comparable to pre-bowel preparation fecal microbiome.	Assessments: Functional Analysis: Functional profiling of the microbiome will be conducted to assess if there are any changes in the metabolic pathways and functions of the microbiome between pre- and post-bowel preparation samples in the subset of CD patients.	24 months
Secondary	Compare the sensitivity and specificity of the microbial analyses from each sample type in their prediction of response to therapy.	Assessments: 1. Sensitivity of Microbial Analyses: Using predictive models developed from microbial and statistical analyses, the sensitivity of microbial analyses from each sample type will be evaluated.; Sensitivity will be reported as the proportion of true positives correctly identified by the analysis.	24 months
Secondary	Compare the sensitivity and specificity of the microbial analyses from each sample type in their prediction of response to therapy.	Specificity of Microbial Analyses: Predictive models will also be used to evaluate the specificity of microbial analyses from each sample type.; Specificity will be reported as the proportion of true negatives correctly identified by the analysis.	24 months