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

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ClinicalTrials.gov Identifier: NCT04760964
Recruitment Status : Recruiting
First Posted : February 18, 2021
Last Update Posted : February 26, 2021
Sponsor:
Information provided by (Responsible Party):
University of Edinburgh

Brief Summary:

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.


Condition or disease
Inflammatory Bowel Diseases

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Study Type : Observational
Estimated Enrollment : 250 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Mitochondrial DAMPs as Mechanistic Biomarkers of Mucosal Inflammation in Crohn's Disease and Ulcerative Colitis (MUSIC)
Actual Study Start Date : January 27, 2021
Estimated Primary Completion Date : February 28, 2023
Estimated Study Completion Date : February 28, 2023

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. The role of mitochondrial DAMPs as an indicator of gut inflammation and mucosal healing [ Time Frame: 12 months ]
    To investigate the role of mitochondrial DAMPs in the clinic as an indicator of gut inflammation and subsequent mucosal healing in response to medical treatment in IBD.


Biospecimen Retention:   Samples With DNA

SALIVA: 1 sample for DNA sampling. BLOOD: At each time point, ~40mls of blood will be taken. Serum for normal IBD care and Mediators/Biomarkers, Serum proteins and LC-MS EDTA tubes for normal IBD care and Mediators/metabolites/biomarkers RNA tube (PAXgene®) for RNA sequencing of host transcriptome ILEO-COLONOSCOPY SAMPLES: Standard research sampling involves: 4 biopsies (2 for formalin fixation and 2 for RNA-later) from ileum (the small bowel), caecum, transverse colon and rectum respectively. Total of 16 biopsies.

STOOL SAMPLES: For Microbiome Next Generation Sequencing/Calprotectin/Stool biomarkers and faecal immunochemical test (FIT)

In selected patients:

BLOOD SAMPLES: 10-20 participants with anticipated high DAMP release. ~10-20 IBD patients with inactive, quiescent disease.

SURGICAL SAMPLES: Surplus tissue may be obtained from specimens of the colon and ileum that have been surgically removed either at the time of operation or during histopathological evaluation.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

All participants will have active IBD at the time of recruitment.

The aim is to capture a wide spectrum of IBD patients with active disease, hence strict criteria for IBD disease severity/extent/activity is not applied.

However, suitable potential participants must have active IBD based on clinical evaluation of referring clinician and any one of the below from investigations which have been carried out within 6 weeks of screening:

  1. FC level of >100ug/g
  2. Blood CRP >5mg/l
  3. Endoscopic, radiological or histological evidence of active IBD

There will be 2 main groups:

  1. IBD patients with acute flare requiring medical treatment (corticosteroids, immunomodulator or biologics)
  2. IBD patients on established medical treatments (biologics or immunomodulators) that require a change due to poor control of disease activity
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04760964


Contacts
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Contact: Gwo-Tzer Ho 01312426653 G.Ho@ed.ac.uk
Contact: Emma Ward e.ward@ed.ac.uk

Locations
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United Kingdom
Ninewells Hospital Not yet recruiting
Dundee, United Kingdom
Contact: Craig Mowat       c.mowat@dundee.ac.uk   
Principal Investigator: Craig Mowat         
Western General Hospital Recruiting
Edinburgh, United Kingdom
Contact: Gwo-Tzer Ho       G.Ho@ed.ac.uk   
Principal Investigator: Gwo-Tzer Ho         
NHS Greater Glasgow & Clyde Not yet recruiting
Glasgow, United Kingdom
Contact: John Paul Seenan       johnpaul.seenan@ggc.scot.nhs.uk   
Principal Investigator: John Paul Seenan         
Sponsors and Collaborators
University of Edinburgh
Investigators
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Principal Investigator: Gwo-Tzer Ho University of Edinburgh
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Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT04760964    
Other Study ID Numbers: AC19037
First Posted: February 18, 2021    Key Record Dates
Last Update Posted: February 26, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Edinburgh:
Crohn's Disease
Ulcerative Colitis
Additional relevant MeSH terms:
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Crohn Disease
Colitis
Colitis, Ulcerative
Inflammatory Bowel Diseases
Mucositis
Inflammation
Ulcer
Pathologic Processes
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Colonic Diseases
Mouth Diseases
Stomatognathic Diseases