Plain English Summary
Background and study aims
Crohn’s disease (CD) is one of the main types of inflammatory bowel disease (IBD), a name given to long-term conditions which causes inflammation (swelling) in the digestive system (gut). Although it can affect any part of the gut, it is most common at the end of the ileum (the last part of the small intestine) or the colon (the large intestine). This can lead to abdominal (belly) pain and diarrhoea, fatigue (extreme tiredness), loss of appetite and weight loss, and feeling generally unwell. People who have severe symptoms of CD are sometimes treated with powerful medicines called anti-TNFs which can be very effective. However, anti-TNFs can occasionally cause life-threatening side effects and are very expensive. Although many patients do improve on these medicines, about half the patients who start treatment will show no improvement after a year, and many continue to be given the medication for long periods of time, with no benefit. It is therefore important to identify a way, at an early stage, to see if the treatment is going to work and, if not, change to a different treatment. This will help patients and may reduce costs to the NHS. The study team has developed a new test using MRI scanning and computer software (mMRI) to monitor the movement of the bowel motility. The more inflamed the bowel is, the less it moves, and initial data suggests that if the motility improves, this might predict a successful response to treatment. The aim of this study is to find out if the changes in motility measuring using MRI (the new test), is better and quicker than current tests (based on blood and stool samples) in predicting if the anti-TNF medicines will still be working after a year.
Who can participate?
Patients aged 16 years and over who have Crohn’s disease and are scheduled to start anti-TNF treatment for the first time.
What does the study involve?
All participants start their anti-TNF treatment as planned. At the beginning of their treatment and then 20-28 weeks and one year later, participants provide blood and stool samples and undergo the MRI-scan to assess their bowel motility, which takes around 40 minutes. If any of the procedures are done as part of standard of care, this will not be repeated as part of the study; instead, the standard procedures will be used, to reduce burden for participants.
What are the possible benefits and risks of participating?
There are no direct benefits involved for those taking part in the study, however the study results could help improve understanding of patient response to anti-TNF therapy which could help future patients. There are no notable risks involved with participating in this study.
Where is the study run from?
University College Hospital (UK)
When is the study starting and how long is it expected to run for?
November 2016 to October 2020
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Miss Zainib Shabir
Miss Zainib Shabir
UCL Comprehensive Clinical Trials Unit
175-176 Tottenham Court Road
+44 207 679 1835
MOTILITY: Small bowel motility quantified by cine MRI as a predictor of long term response in patients with Crohn’s disease commencing biological therapy: A prognostic accuracy study
Early improvements in Small Bowel motility measured using mMRI at 20-28 weeks after anti-TNF therapy initiation better predicts long term response (at 1 year) than current standard clinical tools i.e. measurement of plasma CRP and faecal calprotectin (fC).
Not provided at time of registration
Prospective multi-centre cohort prognostic accuracy study
Primary study design
Secondary study design
Patient information sheet
Eligible patients will be recruited consecutively. All patients will undergo all tests at baseline (prior to beginning the standard anti-TNFalpha therapy), at 20-28 weeks and 1 year after initiation of therapy, unless rendered unnecessary due to clinical non-response to treatment.
Test under evaluation: MRI: a medical imaging technique using magnetic fields and radio frequency waves to generate detailed images of internal body structure. Patients drink liquid to distend the bowel and stimulate movement. Rapid MRI imaging allows “cine” imaging of this bowel motion which will be measured and quantified using the software
Primary comparator: CRP; a blood test that measures plasma concentration of a protein produced by the body in response to inflammation
Secondary comparator: Faecal calprotectin; a stool sample that measures the level of a granulocyte protein that is released into the bowel in response to inflammation
Patients will be followed up for 1 year after starting anti-TNF therapy. They will attend outpatient clinics and for medication infusions where needed, as per the normal routine for their care. The study interventions (MRI, stool and blood tests) and questionnaires will be timed to co-incide with routine clinical visits wherever possible.
Primary outcome measures
Difference in sensitivity between stable or improved segmental small bowel motility versus normalisation of CRP to predict response or remission (RoR) to anti-TNFα therapy at 1 year. Small bowel motility will be measured by MRI and CRP levels via a blood test at 0 and 20-28 weeks.
Secondary outcome measures
1. Difference in specificity between stable or improved small bowel motility versus normalisation of C-reactive protein to predict RoR at 1 year. Small bowel motility will be measured by MRI and CRP levels via a blood test at 0 and 20-28 weeks
2. Difference in area under the receiver operating characteristic curve (ROC AUC) in continuous small bowel motility and in C-reactive protein levels to predict RoR at 1 year. Small bowel motility will be measured by MRI and CRP levels via blood test at 0 and 20-28 weeks
3. Difference in prognostic accuracy to predict clinically significant improvements in each quality of life measure at 1 year between continuous small bowel motility MR score versus changes in C-reactive protein levels . Quality of life will be measured by EQ-5D-5L, CUCQ-8 and IBD-Control 8 questionnaires at 20-28 weeks and 1 year. Small bowel motility will be measured by MRI and CRP levels via blood test at 0 and 20-28 weeks
4. Difference in both sensitivity, specificity and ROC AUC between stable or improved small bowel motility versus normalisation of Faecal Calprotectin predict RoR at 1 year. Small bowel motility will be measured by MRI and calprotectin levels via a stool test at 0 and 20-28 weeks
5. Difference in prognostic accuracy to predict clinically significant improvements in each quality of life measure at 1 year between continuous small bowel motility MR score versus changes in faecal calprotectin levels. Quality of life will be measured by EQ-5D-5L, CUCQ-8 and IBD-Control 8 questionnaires at 0, 20-28 and 52 weeks. Small bowel motility will be measured by MRI and calprotectin levels via a stool test at 0, 20-28 weeks and 52 weeks
6. Difference in prognostic accuracy and incremental prognostic value of multivariate prognostic models for response to anti-TNFα therapy at 1 year between changes in small bowel motility, C-reactive protein and faecal calprotectin. Small bowel motility will be measured by MRI, CRP levels via blood test and calprotectin levels via a stool test at 0 and 20-28 weeks.
7. Interobserver variability of radiologists without prior mMRI experience and experts in MRI imaging . Radiologists will interpret MRI images of small bowel motility at two time points
8. Difference in plasma levels of gut peptides and inflammatory cytokines and small bowel motility variance between patients with and without RoR at 1 year. Small bowel motility will be measured by MRI and gut peptides and inflammatory cytokines will be measured by blood tests at 0, 20-28 and 52 weeks.
9. Difference in small bowel motility variance between patients with normal and elevated levels of gut peptides inflammatory cytokines and between patients with and without abdominal symptoms. Small bowel motility will be measured by MRI, gut peptides and inflammatory cytokines will be measured by blood tests and abdominal symptoms will be measured by CUCQ-8 and IBD-Control 8 questionnaires, all at 0, 20-28 weeks and 52 weeks .
10. Difference in response rates to anti-TNFα therapy at one year for patients with and without skeletal muscle myopenia and patients with and without low skeletal muscle:fat ratios. Skeletal myopenia and muscle fat ratios will be measured using analysis of MRI images at weeks 0, 20-28 and 52.
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Patients aged 16 years or more with active luminal small bowel Crohn’s disease, with or without colonic disease
2. Disease distribution and activity documented by ileocolonoscopy or (for patients with endoscopically-inaccessible disease) magnetic resonance enterography (MRE) performed as part of usual clinical care within the previous 3 months
3. Scheduled to commence anti-TNFα treatment (including biosimilars) for the first time
4. The primary target of therapy, in the opinion of the treating physician, is small bowel disease (with or without treatment of concomitant colonic disease)
Target number of participants
Participant exclusion criteria
1. Primary target of therapy is limited to colonic or perianal fistulising disease
2. mMRI contraindicated (e.g. MRI-incompatible cardiac pacemaker, unable to lie flat, pregnancy)
3. Any psychiatric or other disorder precluding informed consent
4. Small bowel surgery within the preceding 3 months
5. Small bowel stricture causing upstream dilatation on imaging or endoscopy (defined as a >50% increase in diameter in comparison to the adjacent small bowel segment)
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
University College Hospital
235 Euston Road Fitzrovia
National Institute for Health Research
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
IPD Sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
Participant level data
To be made available at a later date
Results - basic reporting