Optimizing Patient Treatment Involving Microbiome Integration for Specialized Therapeutics
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- 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.
Study Overview
Brief 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:
- Can microbiome signatures across different sample types (fecal, intestinal washings, and intestinal epithelial biopsies) predict response to therapy in CD?
- 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:
- Provide fecal and blood samples.
- Undergo intestinal washings and intestinal epithelial biopsy specimens taken during routine colonoscopy.
- Participate in a longitudinal follow-up over 12 months to monitor clinical, biochemical, and endoscopic responses to therapy.
Detailed 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:
- Determine microbiome signatures, across different sample types, in quiescent and active disease for patients with CD living in BC, Canada.
- Evaluate whether fecal, mucosal, and/or intestinal epithelial biopsy microbiome signatures can predict response to therapy.
Methods
Study Design:
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 19 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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).
- •Quiescent disease is defined as an SES-CD <
- •Mild active disease will be defined as a SES-CD of 3-6, or 3 with isolated ileal CD.
- •Moderate/severe active disease will be defined as a simple endoscopic score for CD (SES-CD) ≥ 7 or ≥ 4 for isolated ileal CD.
- •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.
- •Colectomy or Proctocolectomy.
- •Pouch, J-Pouch or Reversed pouch surgery.
- •Short Bowel Syndrome (SBS) diagnosis.
- •Antibiotics in the last 2 months for any indication.
- •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 2 months.
- •Gastroenteritis or travel outside of Canada and the United States in the last month.
- •Pregnant or breastfeeding.
- •Previous bowel surgeries.
Outcomes
Primary Outcomes
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.
Time Frame: 24 months
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
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).
Time Frame: 24 months
* 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).
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).
Time Frame: 24 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).
Secondary Outcomes
- Investigate the correlations between the microbial analyses across different sample types and disease activity in CD.(24 months)
- Compare the difference in microbial analyses within each sample type between active and quiescent CD as well as non-IBD patients.(24 months)
- 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.(24 months)
- Compare the sensitivity of the microbial analyses from each sample type in their prediction of response to therapy.(24 months)
- Compare the specificity of the microbial analyses from each sample type in their prediction of response to therapy.(24 months)
Investigators
Genelle Lunken
Assistant Professor
University of British Columbia