Predicting IBD Treatment Outcomes With Gut Microbiome Analysis

Official title

Optimizing Patient Treatment Involving Microbiome Integration for Specialized Therapeutics

Overview

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.

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:

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.

Interventions

• 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.

Primary outcome measures

• 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]
• 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]
• 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]

Secondary outcome measures (7)

• Investigate the correlations between the microbial analyses across different sample types and disease activity in CD. [Time frame: 24 months]
• Compare the difference in microbial analyses within each sample type between active and quiescent CD as well as non-IBD patients. [Time frame: 24 months]
• Compare the difference in microbial analyses within each sample type between active and quiescent CD as well as non-IBD patients. [Time frame: 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. [Time frame: 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. [Time frame: 24 months]
• Compare the sensitivity of the microbial analyses from each sample type in their prediction of response to therapy. [Time frame: 24 months]
• Compare the specificity of the microbial analyses from each sample type in their prediction of response to therapy. [Time frame: 24 months]

Eligibility criteria

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 <3.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

Canada · 1 center

• GI Research Institute — Vancouver

Publications

• Massaro CA, Meade S, Lemarie FL, Kaur G, Bressler B, Rosenfeld G, Leung Y, Williams AJ, Lunken G. Gut microbiome predictors of advanced therapy response in Crohn's disease: protocol for the OPTIMIST prospective, longitudinal, observational pilot study in Canada. BMJ Open. 2025 Mar 13;15(3):e094280. doi: 10.1136/bmjopen-2024-094280. PMID 40082000

Identifiers

NCT: NCT06453720 · H23-02927

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗