Crohn's Disease - Inflammation and Microbial Proteolytic Activity

Recruiting

• Conditions: Crohn's Disease of Both Small and Large Intestine
• Interventions: Procedure: Colonoscopy

• Registration Number: NCT06503081
• Lead Sponsor: McMaster University

Brief Summary

This study postulates that altered microbiota associated with areas of mucosal inflammation in CD, can be characterized by an increased proteolytic profile. This is clinically important as it may be possible to modulate the proteolytic activity of the CD-associated bacteria by using other bacteria that produce protease inhibitors, such as serpins.

Detailed Description

Crohn's disease (CD), characterized by discontinuous intestinal injury and inflammation, has been associated with changes in the luminal microbiota and impaired barrier function. Previously, the investigators have shown that in patients with CD, the mucosa-associated microbiota is altered. Additionally, it has been shown that in patients with active CD, areas of intestinal injury are associated with impaired barrier function, but the mechanisms remain unclear. Increased host proteolytic activity has been reported in both CD and ulcerative colitis (UC). The microbiota is an important source of proteases with potential inflammatory and barrier disrupting capacity. Indeed, preliminary data indicate that in UC patients the gut microbiota contributes to proteolytic imbalance. It is unknown whether this is also the case in CD. Specifically, this study postulates that the altered microbiota associated with areas of mucosal inflammation in CD, is characterized by an increased proteolytic profile. This is clinically important as it may be possible to modulate the proteolytic activity of the CD-associated bacteria by using other bacteria that produce protease inhibitors such as serpins.

In this prospective observational study, patients booked for routine white light colonoscopy under the care of the Division of Gastroenterology, Hamilton Health Sciences at the McMaster University Medical Centre and Juravinski Hospital Endoscopy Units will be invited to participate. Patients previously diagnosed with Crohn's disease who have a clinical indication for undergoing a standard white light colonoscopy, as determined by the gastroenterologist, will be invited to participate; biopsy samples and mucosal brushings will be taken from inflamed and non-inflamed areas in the ileum or colon.

Study Timeline

• Study Start: 2019-12-01
• Status Verified: 2024-07
• Study First Submitted: 2024-07-09
• Study First Submitted QC: 2024-07-09
• Study First Posted: 2024-07-16
• Primary Completion: 2025-01-01
• Last Update Submitted: 2025-01-08
• Study Completion: 2025-01-10
• Last Update Posted: 2025-01-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Be aged between 18 - 70 years old
• Have a confirmed diagnosis of Crohn's disease
• Have a clinical indication for standard, white light colonoscopy to assess disease activity and extent

Exclusion Criteria

• Inability to provide written informed consent
• Presence of serious life-threatening co-morbidities
• Evidence of toxic megacolon, jaundice, cirrhosis, renal dysfunction, acute GI bleeding
• History of difficult colonoscopy, strictures or extensive diverticulosis
• Antibiotics in the last month
• Probiotics in the last week

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Crohn's disease	Colonoscopy	Patients previously diagnosed with Crohn's disease who have a clinical indication for undergoing a standard white light colonoscopy, as determined by their gastroenterologist, will be invited to participate. Patients undergoing colonoscopy for other indications (for example, for the investigation of possible malignancy, polyps, gastrointestinal bleeding or diarrhea, without colonic inflammation), will not be included in this study.

Primary Outcome Measures

Name	Time	Method
Altered microbiota associated with areas of mucosal inflammation in CD, is characterized by an increased proteolytic profile	December 2019 - January 2025	Increase proteolytic activity profile influenced by microbiota composition in inflamed areas comprared with non-inflamed areas in a context of Crohn's disease

Trial Locations

Locations (1)

McMaster University; 🇨🇦 Hamilton, Ontario, Canada