Mitochondrial DAMPs as Mechanistic Biomarkers of Mucosal Inflammation in Crohn's Disease and Ulcerative Colitis (MUSIC)
The MUSIC study is a multi-centre, longitudinal study set in the real world IBD clinical setting to investigate and develop a new biomarker approach that aims to inform both patients and clinicians of the current state of the affected gut lining (how inflamed or whether the bowel wall has completely healed). This new biomarker approach will study a panel of molecular signs in IBD patients' blood, stools and biopsies that will be correlated to the current gold standard of direct gut visual examination using ileo-colonoscopy and flexible sigmoidoscopy tests (a fibre-optic examination of the lower small bowel and large bowel). Here, the state and appearances of IBD patients' gut lining will be assessed over one year in response to treatment given to them by their NHS IBD consultant. This approach will focus on the role of damage associated molecular patterns (DAMPs), also known as 'danger signals'. DAMPs are found in our own cells and are released during tissue stress or injury. Like signals from bacteria, they can trigger inflammation. In the MUSIC study, blood, stool, saliva and gut samples obtained from participants during active IBD and in clinical remission will be used in order to understand how DAMPs contribute to the development of gut inflammation.
• All patients must be able to give consent and aged 16 years old and over.
• All patients must have a diagnosis of IBD (CD or UC)
• 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
• 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
• 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.
• 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.