MAgnetic Resonance Imaging in COeliac Disease

Completed

• Conditions: Celiac Sprue; Gluten Enteropathy; Celiac Disease; Coeliac Disease
• Interventions: Other: Gluten free diet

• Registration Number: NCT02551289
• Lead Sponsor: University of Nottingham

Brief Summary

One in 100 people suffers from coeliac disease. It affects the lining of the bowel and causes many symptoms such as diarrhoea, wind, stomach pain, constipation and nausea. The only treatment so far is a strict glutenfree diet for life which reverses the bowel damage and often improves symptoms. Up to 25% of patients however may have persistent symptoms despite the gluten free diet but the reasons for this are not clear.

This research aims to help us understand how the gluten free diet works. Investigators will use medical imaging (magnetic resonance imaging or MRI) to measure the volumes of fluid in the small bowel, the size of the large bowel and the time it takes for foods to go through the entire bowel in patients who have just been diagnosed with coeliac disease by their hospital doctor. Investigators will also carry out a breath test and collect a stool sample for basic analysis of the stool bacteria.

Investigators will also collect questionnaires about their feelings and their bowel habits and will try to see how the MRI measurements relate to the patients' symptoms. Investigators will observe how all these measures change after one year of the gluten free diet that doctors will have prescribed as part of the coeliac patients' standard care. As such there is no dietary intervention in this study, investigators will simply study changes in the patients due to their standard treatment. Investigators will also look at a matched group of healthy volunteers to gather a likely reference range of the measurements. This research will be carried out in Nottingham with the help of the specialist coeliac clinics and it will last 3 years. There is a dedicated Coeliac Patient Public Involvement group who have helped plan this study.

Detailed Description

Hypotheses of the study

Based on the investigators' pilot data and on the literature available, this study aims to test the main hypotheses that in adults newly diagnosed with coeliac disease treatment with GFD will:

1. reduce the water content of the fasting small bowel

2. reduce the volume of the fasting colon

3. increase whole gut transit time

Objectives of the study

The specific objectives of the study are therefore to quantify any change following treatment with a gluten-free diet (GFD) in:

1. the water content of the fasting small bowel

2. fasting colon volume

3. whole gut transit time in adults newly diagnosed with coeliac disease using non-invasive MRI Co-variates of interest

During this study investigators will measure a series of exploratory co-variates of interest at diagnosis and at 12 months follow-up:

1. BMI

2. Gastrointestinal symptoms (Bristol Stool diary for a week, HAD, PHQ-15, IBSS, QOL, GI symptoms VAS scales )

3. Marsh grading of D2 segment duodenal biopsies (defined as routine clinical assessment in NUH)

4. Fasting breath hydrogen

5. Serology values (tTG, EMA)

6. Faecal microbiota and short chain fatty acids

In a subgroup analysis, investigators will describe associations (if any) between the MRI outcomes and these co-variates:

1. before treatment,

2. after treatment and

3. differences between the two.

The latter will represent the most useful analysis. By using the after treatment measure as the outcome and the before treatment measure as a covariate this will be mathematically equivalent to analysing the change with treatment (adjusted for baseline).

Parallel Healthy Volunteers group This study will also include a parallel pilot study healthy volunteers (HVs) frequency matched for age (in 20 years bands) and gender to provide descriptive statistics on a likely reference range for the healthy population to inform the design of future studies.

A pilot study in 36 newly diagnosed coeliac disease patients before and after a gluten-free diet.

University based

Pilot study on patients:

There is no data available to estimate the size of the change in water content of the fasting small bowel in patients hence this is a pilot study.

The investigators' own MRI pilot data in n=20 untreated, newly diagnosed coeliac patients showed a fasting small bowel water content of (mean ± SD) 202 ± 115 ml volume. We can predict that we should be able to detect a change of 40% (or a reduction of 80 ml volume) after gluten free diet with a power of 90% and a Type I error probability of 0.05 using n=24 patients in a paired study design. This is considered a clinically significant change after gluten free diet; this change reflects twice the level of normal control values of 65 ± 43 ml volume. Investigators plan to recruit n=36 to allow for dropouts and to increase power also for secondary outcomes.)

Pilot study on healthy volunteers (HVs):

For exploratory purposes and to provide pilot reference data for the design of future studies, investigators aim to collect data on 36 HVs 36 patients and 36 healthy volunteers.

Pilot study in coeliac disease:

Investigations include:

1. Magnetic Resonance Imaging - 2 scans 12 months apart

2. Self-administered symptom questionnaires

3. Stool sample

4. Hydrogen breath test The patients will have had a biopsy and serology as part of their standard care. The healthy volunteers will undergo only the blood sample as part of screening with no biopsy taken.

Duration of study = 36 months. Duration of study for each participant = around 12 months. Follow-up of participants will stop after 12 months if they fail to receive the subsequent MRI scan There is no randomisation or blinding as this is a simple pilot study. Primary endpoint

1. Fasting small bowel water content (SBWC) measured in ml approximately 12 months after initiation of GFD

Secondary endpoints

2. Fasting colon volume measured in ml

3. Whole gut transit time measured in hours

Co-variates analysis as indicated above

The basic characteristics of the study population will be calculated using frequencies and proportions.

Objective 1:

For this cohort of patients with newly diagnosed coeliac disease, investigators will compare the mean difference of their fasting small bowel water content (the primary outcome) before and after the initiation of GFD. This will be done using Paired Test at 5% level of significance. This assumes normality of the data, should the data have a high level of skewness non-parametric methods will be used. In order to assess the potential effect modification with age and gender, investigators will stratify the above analysis by those variables. For this purpose age will be considered as categorical variable and analysed as 20 years bands. This analysis will only be conducted for cases with complete follow-up data on MRI scan.

Objectives 2 and 3:

This analysis will be repeated for the two secondary outcomes, namely the volume of the fasting colon and the gastrointestinal transit time.

Co-variate analyses in the coeliac disease group. The potential association between co-variates (gastrointestinal symptoms, Marsh grading etc.) and the three MRI outcomes will be assessed using stepwise linear regression analysis. Investigators will also assess the magnitude of the effect in term of mean difference along with their respective confidence interval. The analysis would be separately conducted for each outcome and co-variates recorded during the first and the subsequent MRI scan.

Should this analysis highlight a few particularly strong associations, investigators will attempt to input those to a regression model to predict either baseline values or change with GFD.

Pilot study in HVs The HVs group is included to provide pilot reference data to inform the design of future studies. Investigators will compare the small bowel water content among the coeliac disease cases to the HVs (controls), and then compare the mean difference pre- and post-measurement between cases and controls using linear regression.

Study Timeline

• Study First Submitted: 2015-09-08
• Study First Submitted QC: 2015-09-15
• Study First Posted: 2015-09-16
• Study Start: 2016-01
• Primary Completion: 2018-10-19
• Study Completion: 2019-09-30
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-20
• Last Update Posted: 2020-04-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients	Gluten free diet	Patients newly diagnosed with Coeliac disease before starting treatment with a gluten free diet

Primary Outcome Measures

Name	Time	Method
Fasting small bowel water content (SBWC)	12 months	Fasting small bowel water content (SBWC) measured in ml approximately 12 months after initiation of GFD

Secondary Outcome Measures

Name	Time	Method
Colon volume	12 months after initiation of gluten free diet	Fasting colon volume measured in ml
Gut transit time	12 months after initiation of gluten free diet	Whole gut transit time measured in hours

Trial Locations

Locations (1)

NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and the University of Nottingham; 🇬🇧 Nottingham, United Kingdom