Clinical trial NCT06453720: Predicting IBD Treatment Outcomes With Gut Microbiome Analysis
Official title: Optimizing Patient Treatment Involving Microbiome Integration for Specialized Therapeutics
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Inflammatory Bowel Diseases
Crohn Disease
Keywords: IBD
Crohn Disease
Biologic Therapy
Immunology
Gastrointestinal Tract
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: IBD Centre of BC
name: GI Research Institute
name: Pacific Gastroenterology Associates
First posted: 2024-06-12
Enrollment: 100
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The investigators aim to have 75 CD patients complete phase 1 and 2, and 25 non-IBD controls to complete phase 1 only.

Patient grouping for recruitment is as follows:

Group 1: 25 CD in endoscopic remission (SES-CD score \<3) Group 2: 25 CD with moderate to severe endoscopically active disease (SES-CD score ≥7 or ≥4 for isolated ileal CD and at least one large ulcer (≥5mm)) Group 3: 25 CD with mildly endoscopically active disease (SES-CD of 3-6, or 3 with isolated ileal CD, with no large ulcers (≥5mm)) Group 4: 25 age, sex-matched non-IBD controls.

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:

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.

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) ≥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.

Primary outcomes:
measure: 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.
timeFrame: 24 months
measure: 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).
timeFrame: 24 months
measure: 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).
timeFrame: 24 months
Secondary outcomes:
measure: Investigate the correlations between the microbial analyses across different sample types and disease activity in CD.
timeFrame: 24 months
measure: Compare the difference in microbial analyses within each sample type between active and quiescent CD as well as non-IBD patients.
timeFrame: 24 months
measure: Compare the difference in microbial analyses within each sample type between active and quiescent CD as well as non-IBD patients.
timeFrame: 24 months
measure: 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.
timeFrame: 24 months
measure: 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.
timeFrame: 24 months
measure: Compare the sensitivity of the microbial analyses from each sample type in their prediction of response to therapy.
timeFrame: 24 months
measure: Compare the specificity of the microbial analyses from each sample type in their prediction of response to therapy.
timeFrame: 24 months
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: GI Research Institute
state: British Columbia
Study officials:
References: