MAgnetic Resonance Imaging in COeliac Disease

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.

Sex

All

Minimum age

18 Years

Maximum age

65 Years

Inclusion:

Patients newly diagnosed with coeliac disease:

* Male or female
* Able to give informed consent
* Able to schedule the first MRI scan (Visit 2 of the study) within a month of having had a duodenal biopsy and not yet commenced on a gluten free diet.

Inclusion

Pilot study in healthy volunteers:

* Healthy volunteers (without any comorbidities)
* Able to give informed consent

Exclusion Pilot study in patients

* Any past serious, unstable medical condition, unstable/uncontrolled diabetes mellitus, major psychiatric diagnosis
* Any reported history of gastrointestinal surgery that could affect gastrointestinal function (colectomy, small bowel resection)
* Pregnancy declared by candidate
* Contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury
* Reported alcohol dependence
* Unable to stop drugs known to alter GI motility including mebeverine, opiates, monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium channel antagonists during or in the 2 weeks prior to the test. The following medications can be permitted during the course of the study, as long as they have been used at a constant dosage and were commenced at least 1 month prior to the start of the study: birth control pill, or depot intramuscular contraceptive preparation, oestrogen-progesterone replacement therapy, L-thyroxine, lowdose antidepressants (up to 25 mg day) of amitriptyline, nortriptyline, or selective serotonin reuptake inhibitor), or antihypertensive in the diuretic, angiotensin converting enzyme inhibitor or angiotensin II inhibitor classes. Antibiotic or probiotic treatment in the past 4 weeks
* Inability to lie flat or exceed scanner limits of weight \<120kg
* Poor understanding of English language
* Participation of any medical trials for the past 3 months
* Judgement by the PI that the candidate who will be unable to comply with the full study protocol e.g. severe COPD
* Noncompliance to gluten free diet after first, untreated MRI.

Exclusion

Healthy volunteers:

Serology positive test for coeliac disease markers

* Any reported history of gastrointestinal surgery that could affect gastrointestinal function (colectomy, small bowel resection)
* Presence of an intestinal stoma
* Pregnancy declared by candidate
* Contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury
* Reported alcohol dependence
* Unable to stop drugs known to alter GI motility including mebeverine, opiates, monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium channel antagonists during or in the 2 weeks prior to the test. The following medications can be permitted during the course of the study, as long as they have been used at a constant dosage and were commenced at least 1 month prior to the start of the study: birth control pill, or depot intramuscular contraceptive preparation, oestrogen-progesterone replacement therapy, L-thyroxine, lowdose antidepressants (up to 25 mg day1 of amitriptyline, nortriptyline, or selective serotonin reuptake inhibitor), or antihypertensive in the diuretic, angiotensin converting enzyme inhibitor or angiotensin II inhibitor classes.
* Proton Pump Inhibitor (PPI), antibiotic or probiotic treatment in the past 12 weeks
* Inability to lie flat or exceed scanner limits of weight \<120kg
* Poor understanding of English language
* Participation of any medical trials for the past 3 months

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• BACKGROUNDHoad CL, Marciani L, Foley S, Totman JJ, Wright J, Bush D, Cox EF, Campbell E, Spiller RC, Gowland PA. Non-invasive quantification of small bowel water content by MRI: a validation study. Phys Med Biol. 2007 Dec 7;52(23):6909-22. doi: 10.1088/0031-9155/52/23/009. Epub 2007 Nov 8. PMID 18029983
• BACKGROUNDPritchard SE, Marciani L, Garsed KC, Hoad CL, Thongborisute W, Roberts E, Gowland PA, Spiller RC. Fasting and postprandial volumes of the undisturbed colon: normal values and changes in diarrhea-predominant irritable bowel syndrome measured using serial MRI. Neurogastroenterol Motil. 2014 Jan;26(1):124-30. doi: 10.1111/nmo.12243. Epub 2013 Oct 17. PMID 24131490
• BACKGROUNDChaddock G, Lam C, Hoad CL, Costigan C, Cox EF, Placidi E, Thexton I, Wright J, Blackshaw PE, Perkins AC, Marciani L, Gowland PA, Spiller RC. Novel MRI tests of orocecal transit time and whole gut transit time: studies in normal subjects. Neurogastroenterol Motil. 2014 Feb;26(2):205-14. doi: 10.1111/nmo.12249. Epub 2013 Oct 25. PMID 24165044
• BACKGROUNDMarciani L. Assessment of gastrointestinal motor functions by MRI: a comprehensive review. Neurogastroenterol Motil. 2011 May;23(5):399-407. doi: 10.1111/j.1365-2982.2011.01670.x. Epub 2011 Jan 30. PMID 21276139
• DERIVEDCostigan CM, Warren FJ, Duncan AP, Hoad CL, Lewis N, Hill T, Crooks CJ, Morgan PS, Ciacci C, Iovino P, Sanders DS, Hildebrand F, Gowland PA, Spiller RC, Marciani L. One Year of Gluten-Free Diet Impacts Gut Function and Microbiome in Celiac Disease. Clin Gastroenterol Hepatol. 2025 Aug;23(9):1525-1534.e14. doi: 10.1016/j.cgh.2024.11.006. Epub 2024 Dec 9.