Predicting IBD Treatment Outcomes With Gut Microbiome Analysis

NCT06453720 | Recruiting

• 1 other identifier: H23-02927
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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. 1.Can microbiome signatures across different sample types (fecal, intestinal washings, and intestinal epithelial biopsies) predict response to therapy in CD?
2. 2.How do microbiome profiles differ between active and quiescent CD and non-IBD controls?
3. 3.Provide fecal and blood samples.
4. 4.Undergo intestinal washings and intestinal epithelial biopsy specimens taken during routine colonoscopy.
5. 5.Participate in a longitudinal follow-up over 12 months to monitor clinical, biochemical, and endoscopic responses to therapy.

Conditions

Inflammatory Bowel Diseases; Crohn Disease

Keywords

IBD; Crohn Disease; Biologic Therapy; Immunology; Gastrointestinal Tract

Outcome Measures

Primary Outcomes (3)

• 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

• 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). * Mild endoscopically active disease (SES-CD of 3-6, or 3 with isolated ileal CD).

  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).

  * 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 Outcomes (7)

• 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

• 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

• 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

Study Arms (2)

Patients with Crohn's disease

The study will include 75 consenting patients with Crohn's disease, varying in levels of severity depending on assigned SES-CD scoring from their gastroenterologist. These patients will be undergoing routine colonoscopy as per their normal care routine, with this study not requiring additional scheduling commitments. Blood, mucosal washing, and intestinal biopsy samples will be collected during routine colonoscopy procedure. The patient will have the option to collect a stool sample the day before their colonoscopy and bring it to their appointment. They will also receive a sample collection kit during their appointment to collect their next required stool sample in two weeks after their scope.

Procedure: Colonoscopy

Patients without inflammatory bowel disease

The study will include 25 non-IBD age and sex-matched controls to compare data alongside the CD patients. These patients will be undergoing routine colonoscopy as per their normal colon screening routine, with this study not requiring additional scheduling commitments. Blood, mucosal washing, and intestinal biopsy samples will be collected during routine colonoscopy procedure. The patient will have the option to collect a stool sample the day before their colonoscopy and bring it to their appointment. They will also receive a sample collection kit during their appointment to collect their next required stool sample in two weeks after their scope.

Procedure: Colonoscopy

Interventions

Colonoscopy PROCEDURE

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.

Patients with Crohn's disease; Patients without inflammatory bowel disease

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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 ≥ 7 or ≥ 4 for isolated ileal CD). * Group 3: 25 CD with mildly endoscopically active disease (SES-CD of 3-6, or 3 with isolated ileal CD). * Group 4: 25 age, sex-matched non-IBD controls.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of British Columbia: lead
• IBD Centre of BC: collaborator
• GI Research Institute: collaborator
• Pacific Gastroenterology Associates: collaborator

Study Sites (1)

GI Research Institute

Vancouver, British Columbia, V6Z 2K5, Canada

RECRUITING

Related Publications (1)

• 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 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Mucosal washings, intestinal biopsies, whole blood, serum, plasma, stool

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Crohn Disease

Interventions

Colonoscopy

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Central Study Contacts

Fanny LeMarié, PhD

CONTACT

6044414992; flemarie@ibdcentrebc.ca

Mackenzie Melvin, MSc

CONTACT

7788072068; mackenzie.melvin@ubc.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 22, 2024
• First Posted: June 12, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: January 20, 2026

Record last verified: 2026-01

Locations

CA (1)