Condition category
Digestive System
Date applied
19/01/2017
Date assigned
20/04/2017
Last edited
11/01/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Current plain English summary as of 07/01/2019:
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 commence or recommence eligible biological therapies (including biosimilars).

What does the study involve?
All participants start their biological therapy 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 biological 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?
Mrs Anvi Wadke
a.wadke@ucl.ac.uk


Previous 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
ctu.motility@ucl.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Anvi Wadke

ORCID ID

Contact details

Comprehensive Clinical Trials Unit at UCL
Institute of Clinical Trials and Methodology
2nd Floor
90 High Holborn
London
WC1V 6LJ
United Kingdom
020 7907 4687
a.wadke@ucl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

CTU/2014/159

Study information

Scientific title

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

Acronym

MOTILITY

Study hypothesis

Current study hypothesis as of 07/01/2019:
Early improvements in Small bowel motility measured using mMRI at 20 – 28 weeks after biological 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)
Should further information be required, please do let me know.

Previous study hypothesis:
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).

Ethics approval

West Midlands – Edgbaston Research Ethics Committee, 28/04/2017.

Study design

Prospective multi-centre cohort prognostic accuracy study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Condition

Crohn’s disease

Intervention

Current interventions as of 07/01/2019:
Eligible patients will be recruited consecutively. All patients will undergo all tests at baseline (prior to beginning the standard biological 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 biological 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 times to co-incide with routine clinical visists wherever possible.


Previous interventions:
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.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Current primary outcome measure as of 07/01/2019:
Difference in sensitivity between stable or improved MRI-measured segmental small bowel motility versus normalisation of CRP at 20-28 weeks to predict response or remission (RoR) to anti-TNF or anti-interleukin therapy at 1 year.

Previous primary outcome measure:
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

Current secondary outcome measures as of 07/01/2019:
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 including MRI-measured small bowel motility versus those including (i) C-reactive protein and (ii) faecal calprotectin for response to anti-TNFα or anti-interleukin therapy at one year.
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 or anti-interleukin therapy at one year for (a) patients with and without skeletal muscle myopenia and (b) patients with and without low skeletal muscle:fat ratios.
11. Sensitivity and specificity of (a) >10% increase in ADC and (b) >25% reduction in Clermont score between weeks 0 and 20-28 for RoR to biologic therapy at one year.
12. Difference in prognostic accuracy and incremental prognostic value of multivariate prognostic models including change in ADC value derived from DW-MRI between baseline and week 20-28 versus those including (i) C-reactive protein and (ii) faecal calprotectin for response to biologic therapy at one year.
13. Difference in prognostic accuracy and incremental prognostic value of multivariate prognostic models including the Clermont score derived from DW-MRI versus those including (i) C-reactive protein and (ii) faecal calprotectin for response to biologic therapy at one year.
14. Difference in prognostic accuracy between changes in the Clermont score versus changes in (i) C-reactive protein and (ii) faecal calprotectin levels at week 20-28 to predict clinically significant improvements from baseline to one year in each quality of life measure.
15. Incremental prognostic value of DW-MRI parameters in conjunction with motility MRI scores for response to biologic therapy at one year.
16. Difference in prognostic accuracy and incremental prognostic value of multivariate prognostic models including the small bowel ultrasound (SBUS)-derived activity score (SSS) between baseline and week 20-28 versus those including (i) C-reactive protein and (ii) faecal calprotectin for response to biologic therapy at one year.
17. Difference in prognostic accuracy between multivariate prognostic models including the small bowel ultrasound (SBUS)-derived activity score (SSS) between baseline and week 20-28 versus those including (i) motility MRI alone, (ii) DW-MRI alone, and (iii) combined motility+DW-MRI features for response to biologic therapy at one year.


Previous 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

01/11/2016

Overall trial end date

31/10/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Current participant inclusion criteria as of 07/01/2019:
1. Patients aged 16yrs 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), enteric ultrasound (US), computed tomography (CT), barium fluoroscopic follow – through (BaFT) or video capsule endoscopy (VCE) performed as part of usual clinical care within the previous 3 months of starting eligible biological therapy
3. Scheduled to commence or recommence eligible biological treatment (including biosimilars); specifically anti-TNF and anti-interleukin agents.
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).

Previous 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)

Participant type

Patient

Age group

Mixed

Gender

Both

Target number of participants

156

Participant exclusion criteria

Current participant exclusion criteria as of 07/01/2019:
1. Biological therapies other than anti-TNF and anti-interleukin agents, such as anti – integrin therapy (e.g. Vedolizumab)
2. Primary target of therapy is limited to colonic or perianal fistulising disease
3. mMRI contraindicated (e.g. MRI-incompatible cardiac pacemaker, unable to lie flat, pregnancy)
4. Any psychiatric or other disorder precluding informed consent
5. Small bowel surgery within the preceding 3 months
6. 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)

Previous 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

01/05/2017

Recruitment end date

01/05/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University College Hospital
235 Euston Road Fitzrovia
London
NW1 2BU
United Kingdom

Sponsor information

Organisation

University College London

Sponsor details

Gower Street
Kings Cross
London
WC1E 6BT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

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

31/10/2021

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

11/01/2019: The following changes were made: 1. The ethics approval was added. 2. The publication and dissemination plan was added. 07/01/2019: The following changes were made: 1. The plain English summary was updated. 2. The study hypothesis was updated. 3. The interventions were updated. 4. The primary and secondary outcome measures were updated. 5. The plain English summary was updated. 6. The participant inclusion and exclusion criteria were updated. 19/10/2018: Updated public contact email address. 22/09/2017: Internal review.