Diagnostic accuracy of magnetic resonance enterography and intestinal ultrasound for treatment response assessment in Crohn’s disease (MANTRA): protocol for a multicentre, non-randomised, multiple-arm, prospective cohort comparison study

Abstract

Introduction

MR enterography (MRE) and intestinal ultrasound (IUS) are used to assess therapeutic response in Crohn’s disease (CD) follow-up. There is, however, no clear guidance regarding which modality should be used for individual patients or if they are interchangeable. Therefore, clinical practice varies. We will compare the accuracy of MRE and IUS to classify treatment response in CD.

Methods and analysis

Multicentre, non-randomised, multiple arm, prospective cohort study of luminal CD patients aged 16 years or older being treated with steroids, immunomodulators, biologics/biosimilars or small molecules with baseline MRE or IUS. The study will be based in three tertiary referral centres, UK (n=2) and Belgium (n=1), with a target sample size of 155 patients. Patients will undergo both MRE and IUS for response assessment within 20 months of baseline scanning, performed within 6 weeks of each other. One scan will be standard care, the other a research intervention. Interpreting radiologists will be masked to the alternative response assessment test. The primary outcome is the comparative accuracy of MRE and IUS for European Crohn’s and Colitis Organisation-European Society of Gastrointestinal and Abdominal Radiology treatment response group categorisation compared with multidisciplinary consensus panel reference standard, using all available clinical information. Secondary outcomes include the influence of baseline scanning (MRE or IUS) on response characterisation accuracy, response accuracy of MRE and IUS disease activity scoring systems, management impact for each follow-up imaging modality and patient reported preferences.

Ethics and dissemination

This protocol has been approved by the National Health Service Research Ethics Committee and West of Scotland Research Ethics Committee 1 (24/WS/0121). Participant informed written consent will be obtained. Findings will be disseminated by peer-reviewed publications, conference presentations and patient and public involvement collaborators.

Trial registration number

NCT06800326.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• We have designed a multicentre, adequately powered, prospective study using experienced sites with established Crohn’s disease follow-up pathways and robust MR enterography (MRE) and intestinal ultrasound (IUS) services.

• Disease response classification is based on published international, multidisciplinary expert consensus guidelines for optimal practice.

• The accuracy of established MRE and IUS disease activity scoring systems will be assessed in the treatment response setting.

• The reference standards will be defined by a multidisciplinary consensus panel that includes review of clinical, biochemical, endoscopic and/or histopathological data to assess treatment response categories and the theoretical management decision.

• Limitations include variable baseline imaging modality and medical treatment protocol for recruited patients and variability in the timing of follow-up imaging within the permitted 20-month window.

Introduction

Background and rationale

The METRIC study demonstrated that both MR enterography (MRE) and intestinal ultrasoundIntestinal Ultrasound (IUS) have high sensitivity and specificity for diagnosing disease extent and staging Crohn’s disease (96% and 83% for MRE, and 90% and 77% for IUS for active disease presence, respectively), and that patients generally find IUS more tolerable than MRE.¹ Both modalities are therefore used widely to follow-up Crohn’s disease patients to assess therapeutic response.^{2 3} However, there is currently no formal guidance regarding which modality should be selected in this setting. We do not know if MRE and IUS can be used interchangeably for treatment response assessment and practice varies widely regarding which imaging modality is selected and/or available, and whether they are used in isolation or interchangeably.⁴

The imaging signs of disease activity used to assess treatment response have been validated against endoscopic, biochemical and pathological reference standards, with cardinal signs including bowel wall thickening, mural and perimural oedema, ulceration and hypervascularity/neoangiogenesis.^5–7 These signs have more recently been incorporated into multiple validated MRE and IUS disease activity scores.^{5 8} However, even simple measurements, such as bowel wall thickness, are not necessarily equivalent between MRE and IUS given that the physics underlying these modalities differ fundamentally, potentially impacting on image resolution, and differing oral contrast media may influence bowel distension differently. This uncertainty can impede informed management decisions and such considerations assume even greater importance given transmural healing (only assessable using cross-sectional imaging) is an emerging therapeutic target, associated with improved long-term outcomes.^{5 9}

Radiological practice is currently heavily biased towards MRE and IUS provision is relatively sparse in many countries, including the UK.^{4 10} IUS is generally cheaper than MRE, better tolerated by patients and more environmentally sustainable. For these reasons, there is a need to derive high-quality evidence to support greater use of IUS, if appropriate. Indeed, the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the James Lind Alliance and Crohn’s & Colitis UK have all identified this topic as a key research priority.¹¹

However, existing literature is limited and comprised largely of small, underpowered (most comprising fewer than 50 patients), single-centre studies, using inconsistent imaging definitions of treatment response and remission, highly variable reference standards (usually endoscopic alone) and differing follow-up intervals.^12–17 Furthermore, MRE and IUS scores for objective disease assessment are not fully validated in the setting of response assessment with unclear definitions and thresholds for response, and agreement between intermodality scores is not fully understood.^{5 14 18 19}

This multicentre, prospective study will investigate MRE and IUS treatment response classification accuracy against an expert consensus panel and determine if they can be used interchangeably and, if so, in which patients. Study findings could improve imaging modality selection for individual patients and better define care pathways, which in turn may facilitate appropriate management decisions, for example, timely therapeutic de-escalation or escalation. This is critical to avoid irreversible bowel damage from poorly controlled disease and as some therapeutics, such as biologics, have a significant side-effect profile and cost, exacerbated by prolonged administration. Our study may inform optimal Crohn’s disease follow-up imaging pathways for both clinicians and patients. There are also potential implications for service development, resource planning, and training.

Objectives

Primary objective

To compare the accuracy of MRE and IUS to classify treatment response in Crohn’s disease.

Secondary objectives

• To assess whether treatment response classification accuracy using (1) MRE and (2) IUS is influenced by which baseline modality is used.

• To assess the accuracy of established MRE and IUS activity scores to assess treatment response.

• To investigate the relationship between the change in MRE activity score between baseline and follow-up and treatment response classification.

• To assess participants’ perceived importance of different MRE and IUS attributes.

• To assess therapeutic impact by assessing agreement between therapeutic management decisions based on MRE, IUS and clinical data, compared with decisions based on all available data.

• To establish radiologists’ confidence when determining European Crohn’s and Colitis Organisation (ECCO)-ESGAR response category, based on the baseline and follow-up imaging test.

Methods and analysis

Study design

The Diagnostic accuracy of MR Enterography and Ultrasound for Treatment Response Assessment in Crohn’s disease (MANTRA) study is a multicentre, non-randomised, multiple-arm, prospective cohort comparison study. The study protocol has undergone external peer review during ESGAR and Radiological Research Trust grant applications. The study has been registered; Clinicaltrials.gov: NCT06800326.

Study setting

The study will be undertaken in two UK National Health Service (NHS) centres and one academic centre in Belgium. All have established Crohn’s disease multidisciplinary practice, including robust MRE and IUS services, and established referral pathways for response assessment.

Research intervention

An additional, opposing follow-up imaging test, MRE or IUS, was performed depending on which follow-up test has been requested as part of standard clinical care, so that all participants undergo both follow-up MRE and IUS within 6 weeks of each other (figure 1, online supplemental file 1). Based on our prior trial experience, the 6-week interval was chosen to balance the need for contemporaneous imaging with the pragmatics of patients undergoing both imaging tests, for example, MRI appointment availability, patient schedules, etc. We envisage that most recruited patients will undergo both imaging tests at the lower end of the permitted 6-week window and will present the median duration between imaging tests. Follow-up imaging will be compared with either a baseline/pretreatment MRE or IUS performed within the previous 20 months as part of usual clinical care. Although the National Institute for Health and Care Excellence recommendations are for yearly patient treatment monitoring, audit data at recruitment sites revealed variability in practice and this interval accounts for these variations in local practice.²⁰ Audit data suggest most patients are imaged more frequently, and we will present the median interval between baseline/pretreatment and follow-up.

Figure 1. Four potential combinations of baseline and follow-up imaging. *Follow-up imaging within 20 months of baseline as part of standard care. **Follow-up IUS and MRE done within 6 weeks.

Inclusion criteria

• Small bowel or colonic Crohn’s disease on treatment with steroids, immunomodulators, biologics/biosimilars or small molecules.

• 16 years or older.

• Baseline MRE or IUS performed already as part of standard clinical care.

• Follow-up MRE or IUS requested to assess treatment response/disease status on treatment, within 20 months of baseline imaging.

Exclusion criteria

• Resection of diseased segment(s) between baseline/pretreatment imaging and follow-up.

• Inability to provide informed consent.

• Pregnancy.

• Any contraindication or intolerance to MRI.

MR Enterography

We will include all MRE protocols that include a core minimum dataset of sequences. Studies will be performed on 1.5T platforms or higher and use oral contrast as per the local protocol of each site.

Minimum sequence dataset

• Coronal and/or axial balanced steady-state free precession sequence, for example, TrueFISP (True Fast Imaging with Steady State Precession).

• Axial T2-weighted turbo spin echo (TSE).

• Coronal T2-weighted TSE.

• Axial and/or coronal T2-weighted TSE with fat suppression.

Optional sequences

• Axial/coronal diffusion weighted imaging.

• Dynamic TrueFISP cine motility to allow for GIQuant score quantification of motility where possible.²¹

• Coronal and/or axial acquisitions following gadolinium.

Ultrasound

IU at baseline can be performed as per local protocol, which at all sites includes no oral preparation and only fasting for 4–6 hours prior to the scan. Machines from any ultrasound vendor used as part of standard clinical practice will be eligible.

For the follow-up response assessment scan, a standardised scanning protocol will be implemented to facilitate disease activity scoring.¹⁹ All radiologists performing ultrasound will be trained in this standardised scanning protocol during site set up, and an imaging manual will include examples of different IUS parameters and respective degree of severity (online supplemental file 2).

We anticipate that different parameters may be measured at baseline and follow-up IUS because the former is performed pre-enrolment and some aspects cannot be assessed reliably retrospectively. However, when assessable from archived IUS images and/or report, disease activity score parameters will be collected. In contrast, follow-up IUS scan will be performed using a standardised protocol meaning that parameters are consistent between studies.

Imaging interpretation and masking

All study radiologists will have a declared subspecialty interest in gastrointestinal imaging and will be consultant level, with reporting experience of >100 MRE and >100 IUS studies. Both baseline and follow-up imaging tests will be performed and interpreted at each recruitment (figure 1). A minimum of two radiologists will interpret imaging independently at each study site to assess response, one for each of the two follow-up modalities (MRE and IUS), and to enable compliance with the masking protocol.

Specifically, interpreting radiologists will be masked to the opposing follow-up test and clinical details, except for those provided on the request form. They will be unmasked to the baseline MRE or IUS images and original clinical report so they can assess treatment response and finally to all data to assess for any adverse events or uncharacterised incidental findings.

Assessment of ECCO-ESGAR response group

Radiologists will categorise patients into one of the response groups described in the ECCO-ESGAR multidisciplinary expert consensus statement and score their confidence in this decision via a five-point Likert scale.⁶ Response categorisation will be based on predominantly subjective assessment of standard criteria (mirroring clinical practice) such as change in wall thickness, signal/stratification and mesenteric change (table 1). If a mixed response, the decision will be based on the segment least responding. Prior to patient recruitment, all radiologists will attend a training session to agree regarding how categories will be implemented and will receive an imaging manual (table 1, online supplemental file 2). Any pre-specified serious adverse events and previously uncharacterised incidental findings on all imaging will be reported and flagged using standard local procedures.

Table 1. ECCO-ESGAR response group definitions for imaging⁶.

Response category	Definition
Transmural remission	Mural thickness ≤3 mm and resolution of all signs of disease, i.e. mural stratification, mural and extramural oedema.
Significant transmural response	A definite improvement in parameters, i.e. a demonstrable improvement in established activity parameters (eg, wall thickness, Doppler signal, stratification) and/or extent.
Stable disease (3a active or 3b inactive)	No appreciable change.
Progression of inflammation	Unequivocal worsening, i.e. a demonstrable worsening in established activity parameters and/or new penetrating complication.

ECCO, European Crohn’s and Colitis Organisation; ESGAR, European Society of Gastrointestinal and Abdominal Radiology.

Consensus panel decision of reference standard response group and management impact

Multidisciplinary consensus panels will be held at each site, comprised of at least one gastroenterologist and one radiologist who are part of the local clinical care team. Panels will determine the consensus ECCO-ESGAR disease response category for each participant (table 2). An additional clinician (radiologist or gastroenterologist) will be available for arbitration. Consensus panel decisions will occur within 6 months after both treatment response imaging tests have been completed, and after the participant has been assessed in clinic, if planned as part of routine care.

Table 2. ECCO-ESGAR response group definitions for the consensus panel⁶.

Response category	Definition
Transmural remission	Resolution of all signs of disease, i.e. clinical, biochemical, radiologic and endoscopic.
Significant transmural response	A definite improvement in parameters.
Stable disease (3a active or 3b inactive)	No appreciable change.
Progression of inflammation	Unequivocal worsening.

ECCO, European Crohn’s and Colitis Organisation; ESGAR, European Society of Gastrointestinal and Abdominal Radiology.

Panellists will be shown the results of the following four scenarios and asked to (1) determine the ECCO-ESGAR response category and (2) plan a theoretical management decision based on these data with decisions for each scenario recorded and locked before proceeding to the next scenario.

1. Only clinical data collected during standard clinical care, for example, symptoms, drug history, biochemistry (eg, faecal calprotectin, white cell count, C reactive protein), endoscopy where available (including Simple Endoscopic Activity Score for Crohn’s disease where documented^{15 22}), other standard of care imaging (excluding the follow-up MRE or IUS), operative findings where available and histopathology.

2. The above data with the MRE findings disclosed in addition.

3. They will then be asked to disregard the MRE results, the IUS results will be disclosed and any change in the clinical management plan in the light of these recorded. For sequential patients, we will randomise the order that the follow up test is disclosed for each participant.

4. Considering all available data, that is, all clinical data and both MRE and IUS results. This scenario will determine the composite clinical reference standard for response classification (for primary outcome assessment).

The panel will determine two outcomes for each of the four scenarios.

• Reference standard 1: treatment response defined by one of the ECCO-ESGAR response categories and will explain how this category was arrived at.

• Reference standard 2: therapeutic management decision (secondary outcome #5).

We have chosen to use the same panel for each patient to avoid the intrinsic variability in decision making between different consensus panels presented with the same data due to the nuances of treatment planning in Crohn’s disease. The members of the panels will however be varied across the trial duration using a pool of six gastroenterologists and six radiologists.

MRE disease activity scores

On baseline and follow-up imaging, the following established scores will be derived by central radiologists for each small bowel and colonic segment and the rectum.

Simplified Magnetic Resonance Index of Activity

A score will be derived for each bowel segment (0–5) and a global Simplified Magnetic Resonance Index of Activity (s-MaRIA) score produced from a sum of the individual segmental scores (0–25, table 3).^{5 14 23}

Table 3. Calculation of the Simplified Magnetic Resonance Index of Activity.

MRE parameter	Assessment
Bowel wall thickness	Measured in mm using software callipers, scored as abnormal if >3 mm (binary outcome)
Bowel wall oedema	Present if there is increased signal intensity on T2 sequences with fat saturation, compared with normal-appearing loops (binary outcome)
Fat stranding	Present if there is loss of the normal well-defined interface between the bowel wall and mesentery due to oedema/fluid in the perienteric fat (binary outcome)
Ulceration	Present if there is a deep depression in the mucosa and apparent on at least two MRI sequences (binary outcome)
Segmental sMaRIA score	One point for each of bowel wall thickness, oedema and fat stranding; two points for ulceration = 1×bowel wall thickening >3 mm + 1×oedema+1×fat stranding+2×ulcers (maximal score of 5)

s-MaRIA, Simplified Magnetic Resonance Index of Activity.

MRE Global Score

A score for disease activity and bowel damage will be calculated for each bowel segment (jejunum, proximal ileum, caecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum).^{18 24} As per usual practice, a multiplication factor will be applied to this segmental score with an extramural score added to produce a final score (ranging between 0 and 296, table 4).

Table 4. Calculation of the MR Enterography Global Score (MEGS).

Mural parameters	0	1	2	3	Score
Bowel wall thickness	<3 mm	>3–5 mm	>5–7 mm	>7 mm	a
Bowel wall oedema	Normal	Minor increase	Moderate increase	Large increase	b
Perimural T2 hyperintensity (mesenteric oedema)	Normal	Increased signal but no fluid	Small (≤2 mm) fluid rim	Large (>2 mm fluid rim)	c
T1 enhancement (if available) (amount vs normal bowel wall)*	Normal	Minor increase	Moderate increase	Large increase	d
Contrast enhancement (if available) (mural pattern)*	N/A or homogeneous	Mucosal	Layered		e
Haustral loss (colon only)	None	<1/3 segment	1/3 to 2/3 segment	>2/3 segment	f
Mural score for that segment			a+b+c+d+e+f = g
Multiplication factor	1	1.5	2	Total segmental score = g† multiplication factor
Length of disease in that segment	<5 cm	5–15cm	>15 cm
Extramural score	0	5	Score	Total extramural score=i+ii+iii+iv
Lymph nodes (≥1 cm in shortest diameter)	Absent	Present	i
Comb sign†	Absent	Present	ii
Abscess	Absent	Present	iii
Fistulae	Absent	Present	iv
Total score (out of 296) = total segmental score+total extramural score

^*If post intravenous contrast sequences are available, otherwise a modified MEGS score will be calculated.

^†Linear densities on the mesenteric side of affected bowel segments.

International Bowel Ultrasound Segmental Activity Score

Parameters highlighted in table 5 will be used to calculate the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) score which will be derived for each bowel segment.¹⁹

Table 5. Calculation of the International Bowel Ultrasound Segmental Activity Score.

IUS parameter	Score=4 × BWT + 15 × i-fat + 7 × CDS + 4 × BWS
BWT	Quantitative measure in mm
	0	1	2	3
BWS	Normal	Uncertain	Focal (≤ 3 cm)	Extensive (> 3 cm)
i-fat	Absent	Uncertain	Present	N/A
CDS	Absent	Short signals	Long signals inside bowel	Long signals inside and outside bowel

BWS, Bowel wall stratification; BWT, Bowel wall thickness; CDS, Colour Doppler signal; i-fat, Inflammatory fat; IUS, intestinal ultrasound.

Participant questionnaires

Electronic participant questionnaires will be administered within 2 weeks of the last follow-up imaging test. This will use a five-point Likert scale to assess perceived importance of test attributes such as duration, comfort, positioning during testing, the need to drink bowel preparation, speed of report availability and sustainability (online supplemental file 3).

Outcomes

Primary outcome

To compare the difference in sensitivity and specificity for (1) MRE and (2) IUS and to classify treatment response of Crohn’s disease established via a multidisciplinary consensus panel reference standard, using ECCO-ESGAR response categories.

Secondary outcomes

• Secondary outcome #1: primary outcome presented by subgroups defined by whether (a) IUS or (b) MRE is the baseline imaging.

• Secondary outcome #2: sensitivity and specificity of s-MaRIA, MRE Global Score (MEGS) and IBUS-SAS disease activity scores against the reference standard of treatment response (ECCO-ESGAR response categories). Secondary outcome #2 relates to the single values of activity scores at follow-up.

• Secondary outcome #3: to investigate the relationship between any change in MRE activity scores between baseline and follow-up for classification of treatment response, against the reference standard (ECCO-ESGAR response categories). This outcome is limited to the subgroup of participants who have MRE at both baseline and follow-up. Secondary outcome #3 relates to the change in activity scores.

• Secondary outcome #4: participant questionnaire that investigates the value attributed to test related factors such as accuracy, duration and sustainability.

• Secondary outcome #5: to compare the percentage agreement between the therapeutic management decision based on all available data and a theoretical therapeutic management decision using (1) clinical data only, (2) clinical data plus the first follow-up imaging test alone and (3) clinical data plus the second follow-up imaging test alone.

• Secondary outcome #6: to present the distribution of radiologists’ confidence scores when making their response assessment for each of the four different combinations of baseline and follow-up imaging tests.

Statistical analysis plan

Sample size

The target sample size is 155 patients. The sample size calculation is based on the primary outcome and on an 80% power to detect a 15% difference in paired proportions of accuracy (based on a literature search that estimated accuracy of 85% for MRE vs 70% for IUS).^{12 13 15–17 25 26} We assume that 55% of patients are positive on both MRE and IUS (from a retrospective review of 120 consecutive MRE and IUS referrals at the central study site). Recruitment will occur until the target sample size is reached with any reasons for non-trial completion or drop out documented.

Primary outcome

Paired comparison within participants for the difference in (a) sensitivity and (b) specificity between MRE and IUS, with 95% CIs to determine statistical significance. We will present tables for: (1) patients with treatment response by reference standard and (2) patients with no treatment response by reference standard. Each table will be a 2×2 table of MRE and IUS for participants.

Reference standard for therapeutic treatment response consists of ECCO-ESGAR response categories.⁶ Response is defined by transmural remission, stable inactive or significant transmural response. Non-response is defined as stable active or progressive disease.

Secondary outcome 1

Primary outcome presented by subgroups depending on whether (a) IUS or (b) MRE is the baseline imaging test. We will present results using a Forest plot of the difference in (a) sensitivity and (b) specificity, using follow-up imaging between MRE and IUS showing results for participants with (1) IUS baseline and (2) MRE baseline separately. Absolute values for sensitivity and specificity will be presented. The Forest plot will show the subgroup primary outcome estimates with 95% CI. Estimates are the differences between the two imaging modalities.

Secondary outcome 2

Presentation of sensitivity and specificity of s-MaRIA, MEGS and IBUS-SAS disease activity scores against the reference standard (ECCO-ESGAR response categories). Secondary outcome #2 relates to the single values of activity scores at follow-up.

We will present the results using a Forest plot of sensitivity and specificity with 95% CI for (1) active disease, (2) inactive disease and (3) transmural healing. Also, the following activity scores will be used: (a) s-MaRIA, (b) MEGS and (c) IBUS-SAS disease scores using details below. No formal statistical test comparison of activity scores will be used.

The reference standard for treatment response will be categorised as:

1. Active disease, defined as significant transmural response, stable disease or progressive disease.

2. Inactive disease, defined as stable inactive or transmural remission.

3. Transmural healing, defined as the transmural remission group alone.

Thresholds for established activity scores will be defined based on an updated literature review and defined before data lock down and statistical analysis.

Secondary outcome 3

To investigate the relationship between any change in MRE activity scores between baseline and follow-up for classification of treatment response against the reference standard. This outcome is limited to the subgroup of participants who have MRE at baseline and follow-up. Secondary outcome #3 relates to the change in activity scores (s-MaRIA, MEGS, IBUS-SAS).

Results will be presented graphically. In addition, a descriptive summary of sensitivity and specificity will be presented. Published thresholds and pre-specified thresholds for global s-MaRIA and global MEGS will be indicated graphically and used to summarise results using sensitivity and specificity compared with the reference standard.

1. Global s-MaRIA score with a published response threshold of >50% reduction in score.

2. Global MEGS score compared with a pre-specified threshold for response (since there is no currently published threshold value).

‘Treatment response’ is defined as transmural remission or significant transmural response. ‘No treatment response’ is defined as any of stable active, stable inactive or progressive disease.

Secondary outcome 4

Descriptive summary of patient questionnaires, reporting number and percentage of participants by Likert score categories.

Secondary outcome 5

To compare the percentage agreement between the therapeutic management decision based on all available data and a theoretical therapeutic management decision using reference standard #2 using (1) clinical data only, (2) clinical data plus the first follow-up imaging test alone (either IUS or MRE) and (3) clinical data plus the second follow-up imaging test alone (either IUS or MRE). MRE and IUS classifications will be cross tabulated within patients using 2 by 2 tables for each reference standard grouping.

A paired comparison of the difference in the percentage correct between MRE and IUS will be presented with 95% CI. The 95% CI will be used to determine the statistical significance.

Secondary outcome 6

Graphical presentation of the distribution of radiologist reported confidence scores of ECCO-ESGAR response category for each of the four different combinations of baseline/pretreatment and follow-up imaging tests.

Patient and public involvement

We are collaborating with IBDrelief, a digital healthcare agency for inflammatory bowel disease (IBD) patients. IBDRelief have helped develop the study outcomes, design and acceptability, so that they are focused on patient concerns. IBDrelief representatives will sit on the trial management group and will be involved in interpretation of findings, write-up and dissemination. PPI feedback on the MANTRA study design includes using a questionnaire regarding patient experience of MRE and IUS, and their priorities when considering an imaging test, for example, duration, report availability, comfort and sustainability. This online questionnaire has been reviewed and edited by members of the PPI group.

Their comprehensive patient network will help disseminate study findings to the general public.

Ethics and dissemination

Ethical approval

The MANTRA study obtained approval from NHS Research Ethics Committee and West of Scotland Research Ethics Committee 1 (24/WS/0121) on 21 August 2024 (IRAS 331175) and will be conducted in accordance with the principles of Good Clinical Practice. Informed consent is a requirement. University College London is the study sponsor.

Dissemination plans

Study results will be shared via conference presentations and multiple peer-reviewed publications. Publications will contain no individual patient level data or identifiers. The PPI group contributed to our dissemination plans, including to consented participants via direct correspondence, and the wider public via the IBDrelief online platform and social media with a growing number of other IBD patient groups and charities.

Trial status

Recruitment began in October 2024. We anticipate study closure to recruitment and other local site tasks by the first quarter of 2027.