Investigating biomarkers for inflammation in Crohn's Disease and Ulcerative Colitis

Mitochondrial DAMPs as Mechanistic Biomarkers of Mucosal Inflammation in Crohn's Disease and Ulcerative Colitis (MUSIC)

This study is trying to find new signs of gut inflammation in people with Crohn's Disease and Ulcerative Colitis by looking at blood, stool, and tissue samples to see how they relate to standard tests over a year.

Quick facts

• Study type: Observational
• Enrollment: 250 (estimated)
• Sex: All
• Sponsor: University of Edinburgh (Academic / other)
• Locations: 3 sites (Dundee and 2 other locations)
• Trial ID: NCT04760964 on ClinicalTrials.gov

What this trial studies

This observational study aims to develop a new biomarker approach to assess mucosal inflammation in patients with inflammatory bowel diseases (IBD) such as Crohn's Disease and Ulcerative Colitis. It will analyze molecular signs found in blood, stool, and biopsies, correlating these with the results from standard ileo-colonoscopy and flexible sigmoidoscopy examinations. The study will focus on mitochondrial damage-associated molecular patterns (DAMPs) as potential indicators of gut inflammation and healing over a one-year period in response to treatment. By improving the understanding of mucosal healing, the study seeks to enhance patient management and treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates for this study are patients aged 16 and older with a diagnosis of active inflammatory bowel disease.

Not a fit: Patients with inactive IBD or those unable to provide consent may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more accurate method for assessing mucosal healing in IBD patients, leading to better treatment decisions.

How similar studies have performed: While the approach of using DAMPs as biomarkers is innovative, similar studies have shown promise in improving the understanding of inflammation in other contexts.

Eligibility criteria

Inclusion Criteria:

1. All patients must be able to give consent and aged 16 years old and over.
2. All patients must have a diagnosis of IBD (CD or UC)
3. All patients must have active IBD at the time of screening:

   • Active IBD symptoms by referring clinician's judgement in addition to one of the below criteria (within 6 weeks of screening):
   * FC level of \>100ug/g
   * Blood CRP \>5mg/l
   * Endoscopic, radiological or histological evidence of active IBD
4. All IBD patients with disease involvement that is amenable for endoscopic assessment of mucosal healing. This includes:

   * CD patients with previous ileal or colonic surgical resection
   * CD patients with perianal disease where ileo-colonoscopy or sigmoidoscopy are not contraindicated
   * CD patients with ileal involvement only where endoscopic disease activity can be recorded
5. All IBD patients will require a recent ileo-colonoscopy or flexible sigmoidoscopy within 6 weeks of recruitment that has:

   * Clear documentation of endoscopic disease activity and extent (SES-CD and Rutgeert's score for CD; Mayo Score or UCEIS for UC)
   * Photographs of endoscopic mucosal IBD disease activity
   * If there is not a recent ileo-colonoscopy or flexible sigmoidoscopy, the participant will be asked to undergo an ileo-colonoscopy or flexible sigmoidoscopy at baseline.
6. If patients have undergone an ileo-colonoscopy or flexible sigmoidoscopy within 6 weeks but with an endoscopic report that is insufficient in endoscopic disease activity data as per (5), potential participant can still be considered providing there is:

   * Supporting objective evidence of IBD disease activity (FC, CRP) within 2 weeks of index ileo-colonoscopy or flexible sigmoidoscopy.

Exclusion Criteria:

1. IBD patients with severe/fulminant disease at screening:

   * Subjects with colitis fulfilling the Truelove and Witts' criteria (stool frequency \>6/24 hours with all of the features of fever \>38C, pulse rate \>100 beats per minute, blood haemoglobin \<105 g/l, albumin \<30g/l)
   * Subjects displaying evidence of toxic megacolon (transverse colon diameter \>6m on plain abdominal X-ray with accompanying full radiological report). Note - abdominal X-ray will be carried out if clinically indicated by referring clinician
   * Evidence of significant bowel obstruction, abdominal sepsis, abscess formation and fistula formation (bowel or perianal) as documented by referring clinician that is supported by clinical, radiological and blood laboratory investigations
2. Referring clinician's judgement where surgical intervention (colectomy or resection) is deemed likely within 3 months of screening
3. Evidence of intestinal dyplasia or malignancy (histologic, endoscopic or radiologic)
4. UC patients with limited involvement of the rectum (\<15cm - proctitis)
5. UC patients who have had a colectomy (total and subtotal)
6. UC patients with an ileo-anal pouch
7. IBD (UC, CD or IBD-U) with an intestinal stoma
8. Patients where ileo-colonoscopy or flexible sigmoidoscopy are contra-indicated (e.g. significant co-morbidities e.g. cardiovascular, respiratory, cancer, renal failure; and pregnancy)
9. Participants where there are limitations to language communication where there is a potential issue where information sheet cannot be reliably understood and/or the subject cannot provide full informed consent.

Where this trial is running

Dundee and 2 other locations

• Ninewells Hospital — Dundee, United Kingdom (Not_yet_recruiting)
• Western General Hospital — Edinburgh, United Kingdom (Recruiting)
• NHS Greater Glasgow & Clyde — Glasgow, United Kingdom (Not_yet_recruiting)

Study contacts

• Principal investigator: Gwo-Tzer Ho — University of Edinburgh
• Study coordinator: Gwo-Tzer Ho

Conditions Inflammatory Bowel Diseases; Crohn's Disease; Ulcerative Colitis