Diagnostic Concordance of MR Enterography and Ultrasound for Treatment Response Assessment in Crohn's Disease (MANTRA)

Diagnostic Concordance of MR Enterography and Ultrasound for Treatment Response Assessment in Crohn's Disease (MANTRA): a Multicentre, Non-randomised, Multiple-arm, Prospective Cohort Comparison Study

Crohn's disease is a lifelong condition resulting in inflammation of the bowel. Treatment with powerful drugs aim to reduce inflammation by suppressing the immune system. It is important to regularly assess if the drugs are effective, so they can be stopped or changed if not.

There are several ways doctors assess if the medication is effective as just relying on how the patient feels is not sufficient. Blood and stool tests looking for inflammation are useful but have limitations. Looking into the bowel using endoscopy is effective but very invasive. Medical imaging notably MR Enterography (MRE), a type of MRI scan, and intestinal ultrasound (IUS) visualise the bowel, and are safe, non-invasive and generally well tolerated tests frequently used in the NHS to assess how well treatment is working.

There is however wide variation in which imaging test is selected without clear guidance. The investigators currently do not know if one is better in assessing response to treatment, and if they can be used interchangeably.

The proposed study will investigate this question to guide the future care of Crohn's disease patients. The investigators will recruit patients having follow up imaging tests to assess their treatment and ask them to undergo both MRE and IUS. Radiologists will interpret the MRE and IUS, unaware of the findings of the other test, and state if the disease is improving or not. The doctors looking after the patient will then look at all available information e.g. symptoms, blood/stool tests, colonoscopy, and decide if the patient is the same, worse or better on the medication. This decision will be used to establish how accurate MRE and IUS are in assessing response, how often they agree and if they can be used interchangeably in the future, for example based on patient preference or availability at the hospital.

Study Overview

• Status: Recruiting
• Conditions: Crohn Disease
• Intervention / Treatment: Diagnostic test: Ultrasound; Diagnostic test: MRE Scan

Detailed Description

Imaging, typically with MR enterography (MRE) and/or Intestinal Ultrasound (IUS), is central in the follow up of Crohn's disease patients to assess treatment response to powerful immunosuppressive therapy. Practice varies widely on which imaging modality is selected and/or available and if they are used in isolation or interchangeably. There is currently no set guidance and practice varies widely.

We know that both MRE and IUS are accurate for diagnosing and staging Crohn's disease, although patients generally prefer IUS if it is of comparable accuracy. We however do not understand if MRE and IUS can be used interchangeably for treatment response assessment. Such uncertainty can impede patients and clinical teams in making informed management decisions.

Currently, IUS provision is sparse with no formal training programme, leading to a heavy bias for MRE. This approach is more costly, less tolerable to patients, adds pressure to already overloaded MRI workflows, and less environmentally sustainable. The current study may support the drive for comprehensive provision of both MRE and IUS services and training.

Currently, the literature is very limited and largely comprised of small single centre studies (most less than 50 patients), using inconsistent imaging definitions of treatment response, highly varied reference standards and differing follow up intervals. There are several MRE and IUS scores for objective disease assessment which remain to be fully validated for response and their respective agreement is not fully understood.

Ultimately, a major outstanding research question is not if investigators should use MRE or IUS, but rather, when investigators should use them in the management of individual patients. Accordingly, the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) and the James Lind Alliance/Crohn's & Colitis UK identify the current study topic as a key research priority.

The proposed prospective study will be the largest to date to investigate the accuracy of MRE and IUS for classification of treatment response against an expert consensus panel, their agreement in response assessment.

• Study Type: Observational
• Enrollment (Estimated): 155

Contacts and Locations

• Study Contact: Name: Katerina Soteriou; Email: katerina.soteriou@nhs.net
• Study Contact Backup: Name: Maira Hameed; Phone Number: 020 7679 9274; Email: maira.hameed@ucl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • University College London Hospitals
    • Contact: Michelle Berin; Phone Number: 0203456789; Email: michelle.berin1@nhs.net
    • Principal Investigator: Maira Hameed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients will be male and female from 16 years and above who have small bowel or colonic Crohn's disease.

Description

Inclusion Criteria:

• Small bowel or colonic Crohn's disease
• 16 years or older
• Baseline/pre-treatment MR Enterography or Intestinal Ultrasound already performed as part of standard clinical care
• Follow up MR Enterography or Intestinal Ultrasound requested to assess treatment response within 15 months of baseline/ pre-treatment imaging

Exclusion Criteria:

• Interval resection of diseased segment(s)
• Inability to achieve informed consent
• Pregnancy
• Any contraindication/ intolerance to MRI

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ultrasound Scan; An additional follow up IUS i.e. all participants undergo both a follow up MRE and IUS, with no participant randomisation. The cohort under US would have had an MRE as part of their standard of care.	Diagnostic test: Ultrasound; Participants will have either an ultrasound or magnetic resonance imaging, depending on what scan they have had as part of their standard of care.; Diagnostic test: MRE Scan; Participants will have either an ultrasound or magnetic resonance imaging, depending on what scan they have had as part of their standard of care.
MRE Scan; An additional follow up MRE i.e. all participants undergo both a follow up MRE and IUS, with no participant randomisation. The cohort under MRE would have had an IUS as part of their standard of care.	Diagnostic test: Ultrasound; Participants will have either an ultrasound or magnetic resonance imaging, depending on what scan they have had as part of their standard of care.; Diagnostic test: MRE Scan; Participants will have either an ultrasound or magnetic resonance imaging, depending on what scan they have had as part of their standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome Measure	The primary outcome will measure the difference in the percentage correct treatment response classification using MR Enterography (MRE) and Intestinal Ultrasound (IUS), against a multidisciplinary consensus panel reference standard.	18 months

Collaborators and Investigators

• Sponsor: University College, London
• Investigators: Principal Investigator: Stuart Taylor, UCLH

Publications and helpful links

General Publications

• Radford SJ, Taylor S, Moran G. Ultrasound use to assess Crohn's disease in the UK: a survey of British Society of Gastroenterology Inflammatory Bowel Disease Group members. Frontline Gastroenterol. 2022 Jan 18;13(6):471-476. doi: 10.1136/flgastro-2021-102065. eCollection 2022.
• Taylor SA, Mallett S, Bhatnagar G, Baldwin-Cleland R, Bloom S, Gupta A, Hamlin PJ, Hart AL, Higginson A, Jacobs I, McCartney S, Miles A, Murray CD, Plumb AA, Pollok RC, Punwani S, Quinn L, Rodriguez-Justo M, Shabir Z, Slater A, Tolan D, Travis S, Windsor A, Wylie P, Zealley I, Halligan S; METRIC study investigators. Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn's disease (METRIC): a multicentre trial. Lancet Gastroenterol Hepatol. 2018 Aug;3(8):548-558. doi: 10.1016/S2468-1253(18)30161-4. Epub 2018 Jun 18.
• Rimola J, Torres J, Kumar S, Taylor SA, Kucharzik T. Recent advances in clinical practice: advances in cross-sectional imaging in inflammatory bowel disease. Gut. 2022 Dec;71(12):2587-2597. doi: 10.1136/gutjnl-2021-326562. Epub 2022 Aug 4.
• Novak KL, Nylund K, Maaser C, Petersen F, Kucharzik T, Lu C, Allocca M, Maconi G, de Voogd F, Christensen B, Vaughan R, Palmela C, Carter D, Wilkens R. Expert Consensus on Optimal Acquisition and Development of the International Bowel Ultrasound Segmental Activity Score [IBUS-SAS]: A Reliability and Inter-rater Variability Study on Intestinal Ultrasonography in Crohn's Disease. J Crohns Colitis. 2021 Apr 6;15(4):609-616. doi: 10.1093/ecco-jcc/jjaa216.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: July 29, 2024
• First Submitted That Met QC Criteria: January 28, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 28, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: 172896

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No