Exploring biomarkers of mucosal inflammation in paediatric Crohn’s disease (Mini-MUSIC)
| ISRCTN | ISRCTN14273559 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14273559 |
| IRAS number | 321507 |
| Secondary identifying numbers | AC23012, CPMS 59890 |
- Submission date
- 28/06/2023
- Registration date
- 24/03/2025
- Last edited
- 07/04/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Digestive System
Plain English summary of protocol
Background and study aims
Inflammatory bowel disease (IBD) comprising of Crohn’s disease (CD), ulcerative colitis (UC) and IBD-unclassified (IBD-U) are chronic, incurable immune-mediated conditions affecting the gastrointestinal tract. Despite recent progress in identifying factors that increase one’s likelihood to develop IBD (e.g. genetics), or that can trigger (e.g. drugs, stress) a flare, we do not understand why gut inflammation seen in IBD does not resolve. Paediatric IBD (PIBD) tends to be more aggressive with patients typically presenting with more extensive areas of the bowel affected while having higher hospitalisation and colectomy rates. The current gold standard for monitoring is endoscopy however, this carries issues of poor patient tolerance, associated complications and usage of finite NHS resources. These are compounded in paediatrics due to the need for patients to receive general anaesthesia for the procedure.
The Mini-MUSIC study is a multi-centre, longitudinal, translational research study set in the real-world PIBD clinical setting to investigate and develop a new biomarker (a biological signal of a normal or abnormal process, condition or disease) 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 PIBD patients’ blood, stools and biopsies that will be correlated to clinical status, disease activity, systemic inflammatory activity and mucosal state (by non-invasive faecal calprotectin) - and in some cases, the direct appearances (via endoscopy and histopathology) of PIBD patients’ gut lining will be assessed over 1 year in response to current standard nutritional and drug treatment given to them by their NHS PIBD consultant.
Who can participate?
Patients aged 6-17 years old with inflammatory bowel disease in Scotland
What does the study involve?
Patients will be followed longitudinally at three time points over the course of one year. Each visit will include a detailed clinical assessment and biological sampling (blood, stool, saliva). If patients are receiving an endoscopy as part of their standard NHS care additional biopsies will be taken.
What are the possible benefits and risks of participating?
There are no direct benefits to the participants other than the knowledge that their inclusion is contributing to the advancement of knowledge around their condition. The risks are minimal and related to biological sampling including pain around venepuncture. The current understanding is that the additional biopsies taken during endoscopy do not infer additional risk.
Where is the study run from?
Child Life and Health, Royal Hospital for Children and Young People, Edinburgh, and the Centre for Inflammation Research, Queen Mother's Research Institute, Edinburgh. The research is based in all children's hospitals across Scotland (Edinburgh, Glasgow, Dundee, Aberdeen).
When is the study starting and how long is it expected to run for?
January 2023 to December 2026
Who is funding the study?
The study is funded through a charitable donation through the Edinburgh Children's Hospital Charity (Scotland)
Who is the main contact?
Dr Gwo-Tzer Ho (Chief Investigator, Consultant Gastroenterologist), g.ho@ed.ac.uk
Professor David Wilson (Principle Paediatric investigator)
Dr David Wands (Research Fellow), dwands@ed.ac.uk
Contact information
Public
Child Life and Health
Royal Hospital for Children and Young People
50 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom
 ORCID ID |
0000-0002-2500-6041 |
|---|---|
| Phone | +44 (0)7951491946 |
| dwands@ed.ac.uk |
Principal Investigator
Institute for Regeneration and Repair
Centre for Inflammation Research
Edinburgh Bioquarter
Edinburgh
EH16 4UU
United Kingdom
| ORCID ID |
0000-0002-6014-372X |
|---|---|
| Phone | +44 (0)131 536 1000 |
| g.ho@ed.ac.uk |
Principal Investigator
Child Life and Health
Royal Hospital for Children and Young People
50 Little France Cresent
Edinburgh
EH16 4TJ
United Kingdom
| Phone | +44 (0)7584904453 |
|---|---|
| d.c.wilson@ed.ac.uk |
Study information
| Study design | Multi-centre longitudinal observational cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Longitudinal study |
| Study setting(s) | Hospital, Laboratory |
| Study type | Diagnostic |
| Participant information sheet | 43859_PIS_ParentGuardian_v1.1_15May23.pdf |
| Scientific title | Mitochondrial DAMPs as mechanistic biomarkers of mucosal inflammation in paediatric Crohn’s disease and ulcerative colitis |
| Study acronym | Mini-MUSIC |
| Study objectives | Recently, it was found that damage-associated molecular pattern (DAMPs) arising from the mitochondria are increased in patients with active inflammatory bowel disease (IBD). Mitochondria are the ‘batteries’ or ‘power stations’ that reside within and provide energy for living cells. They have evolved from bacteria around 2-3 billion years ago. As such, the mitochondria have many similarities with bacteria. When our immune cells encounter mitochondria that are released, they confuse them with bacteria, become activated and trigger a prolonged inflammatory response, which is destructive to our own tissue. Of interest, it has been shown that these signals are mitochondrial DNA and fragments of their protein, called formylated peptides. Mitochondrial DAMPs can also be released in severe acute tissue damage or inflammation (for example, in major trauma or sepsis respectively). The hypothesis for this study is that mitochondrial DAMPs could be used as biomarkers in chronic immune-mediated conditions such as IBD. |
| Ethics approval(s) |
Approved 22/05/2023, Health and Social Care Research Ethics Committee A (HSC REC A) (Office for Research Ethics Committees Northern Ireland (ORECNI), Lissue Industrial Estate West, 5 Rathdown Walk, Lisburn, BT28 2RF, United Kingdom; +44 (0)28 95 361400; info.orecni@hscni.net), ref: 23/NI/0062 |
| Health condition(s) or problem(s) studied | Paediatric inflammatory bowel disease |
| Intervention | This is a multi-centre longitudinal observational cohort study following paediatric inflammatory bowel disease patients, aged 6-17 years, with clinical assessment and biological sampling at three-time points over one year (0, 3 and 12 months). They will undergo a clinical assessment at each time point, including height, weight and a symptom questionnaire carried out by the study team or local clinical research facility team. Biological sampling will also occur at each visit, including blood and optional saliva and stool samples. If the patient is admitted to the hospital unexpectedly for a flare of their disease or surgery then a further disease assessment with biological sampling will take place. The study ends for the participant after their 12-month visit. Detailed clinical and phenotypic data Biological sampling including blood (cfDNA, RNA, plasma, standard disease biomarkers - CRP/ESR/FBC); saliva for microbiome analysis; stool for microbiome analysis; and gut biopsies for transcriptomics and microbiome analysis Primary outcomes include: Assessing the utility of mitochondrial DAMPs as prognostic and mechanistic biomarkers in inflammatory bowel disease Secondary outcomes include: Assessing oral-gut microbiome signatures |
| Intervention type | Other |
| Primary outcome measure | Each of the following primary outcome measures will be assessed at 0, 3 and 12 months plus any additional admissions to the hospital: 1. Full blood count (FBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels measured using blood tests 2. Biological sampling including blood (cfDNA, RNA, plasma, standard disease biomarkers - CRP/ESR/FBC); saliva for microbiome analysis; stool for microbiome analysis; and gut biopsies for transcriptomics and microbiome analysis Disease course and severity will be recorded using the study's case report forms Height will be measured using a tape measure Weight will be measured using scales Blood will be taken by venepuncture by the research team Saliva will be collected in a specialised tube by the patient and given to the research team Stool samples will be collected in a specialised tube by the patient and given to the research team |
| Secondary outcome measures | Oral-gut microbiome signatures measured using saliva and stool collected in specialised tubes by the patient and given to the research team at 0, 3 and 12 months plus during any additional admissions to the hospital |
| Overall study start date | 04/01/2023 |
| Completion date | 31/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 6 Years |
| Upper age limit | 17 Years |
| Sex | Both |
| Target number of participants | 120 |
| Key inclusion criteria | 1. Aged 6 - 17 years old 2. A diagnosis of IBD (CD, UC or IBD-U) 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 following 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 new diagnosis PIBD patients will require a recent ileo-colonoscopy within 6 weeks of recruitment that has: 4.1. Clear documentation of endoscopic disease activity and extent (SES-CD for CD; Mayo Score for UC) 4.2. Photographs of endoscopic mucosal IBD disease activity 5. If patients have undergone an ileo-colonoscopy within 6 weeks but with an endoscopic report that is insufficient in endoscopic disease activity data as per (4), potential participants can still be considered providing there is: 5.1. Supporting objective evidence of IBD disease activity (FC, CRP) within 2 weeks of index endoscopic assessment 6. Patients who have evidence of an active IBD flare (as per 3) or are changing IBD therapies due to treatment failure can be included in the study without a recent ileo-colonoscopy if the referring clinician considers omitting it as their local standard of care. |
| Key exclusion criteria | Does not meet the inclusion criteria |
| Date of first enrolment | 01/01/2024 |
| Date of final enrolment | 31/12/2025 |
Locations
Countries of recruitment
- Scotland
- United Kingdom
Study participating centres
Glasgow
G51 4TF
United Kingdom
Edinburgh
Lothian
EH16 4TJ
United Kingdom
Aberdeen
AB25 2ZG
United Kingdom
Dundee
DD1 9SY
United Kingdom
Sponsor information
Research organisation
Academic and Clinical Central Office for Research and Development (ACCORD)
NHS Lothian and the University of Edinburgh
47 Little France Crescent
Edinburgh
EH16 4TJ
Scotland
United Kingdom
| Phone | +44 (0)131 536 1000 |
|---|---|
| enquiries@accord.scot | |
| Website | https://www.accord.scot/ |
"ROR" |
https://ror.org/01x6s1m65 |
Funders
Funder type
Charity
No information available
Results and Publications
| Intention to publish date | 31/12/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from Dr David Wands, dwands@ed.ac.uk |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 1.1 | 15/05/2023 | 05/07/2023 | No | Yes |
| Protocol file | version 1.0 | 18/04/2023 | 05/07/2023 | No | No |
Additional files
Editorial Notes
07/04/2025: The following changes were made:
1. The target number of participants was changed from 60.
2. The recruitment start date was changed from 01/07/2023 to 01/01/2024.
3. The recruitment end date was changed from 01/07/2024 to 31/12/2025.
4. The overall study end date was changed from 01/07/2025 to 31/12/2026.
5. The intention to publish date was changed from 01/07/2026 to 31/12/2027.
01/04/2025: Internal review.
05/07/2023: Trial's existence confirmed by the Health and Social Care Research Office for Research Ethics Committees Northern Ireland (UK).
