Magnetic Resonance Imaging of Motility in Crohn's 2
Condition: Crohn Disease
MeSH terms: Crohn Disease
Study type: Interventional

Summary: 
      Crohn's disease (CD) is becoming more common. One of the main features of this disease is
      weight loss and malnutrition with symptoms such as tummy aches and bloating. These problems
      have a strong negative effect on the patients' quality of life but the causes of these
      problems are not well understood. Enteroendocrine cells are nutrient sensors in the bowel
      that secrete special chemicals (called hormones) that control appetite and the movements all
      the gut. The investigators think that this control mechanism goes wrong in Crohn's patients
      and they have set off to do more research on this. Looking at the inside work of the gut has
      always been difficult and at times unpleasant for patients, however recent developments in
      magnetic resonance imaging (MRI) are allowing the investigators to study the workings of the
      gut in greater detail and without discomfort for the patients.

      Our main objective is to investigate the difference in small bowel motility between CD
      patients with active ileal disease and healthy volunteers.
    

Detailed description: 
      Background: Poor nutrition in Crohn's disease (CD) is common but poorly understood. Apart
      from disease burden and repeated surgery, reduction in appetite might be an aetiological
      factor.

      Enteroendocrine cells (EC) are intraluminal nutrient sensors. They play a pivotal role in
      orchestrating physiological functions in the gastrointestinal tract. Sensing the nutrient
      content of the lumen, they secrete multiple peptides and amines that control gut secretory
      and motor functions. CD patients with small bowel inflammation show increased expression in
      EC peptides with exaggerated postprandial responses in anorectic EC hormones. This is
      associated with symptoms of nausea and anorexia, with EC-peptide expression decreasing to
      normality in remission.

      There has been a longstanding interest on the effect of CD on gastric emptying and
      gastrointestinal motility. Recent technological advances have allowed us to use magnetic
      resonance imaging (MRI) to measure both disease activity and intestinal motility.

      Reduced intestinal motility has been recently shown in CD patients with active terminal ileal
      disease. A significant negative correlation is observed between terminal ileal motility and
      histological, biochemical and radiological measures of disease activity. Intestinal
      hypomotility may be observed in proximal unaffected segments of small bowel as well.

      An increase in EC activity could potentially lead to altered appetite and symptoms of nausea
      through delayed gastric emptying and most importantly delayed small bowel transit. This
      mechanistic link has not been described and present findings have not been correlated to
      patient symptoms. This work can potentially open a new therapeutic pathway in CD therapy.
      Optimisation studies in healthy volunteers (HV) are urgently needed.

      Aims & Hypothesis: In intestinal inflammation due to CD, the observed up-regulation of
      fasting and postprandial EC peptides may correlate with a delayed whole gut transit
      specifically small bowel transit and gastric emptying.

      Experimental protocol and methods: 15 Crohn's patients and 20 Healthy volunteers will be
      recruited. Standard MRI exclusion criteria will apply.

      This study will have an open-label design. The subjects will be asked to fast from 2000 h.
      They will be asked to fill in a questionnaire to ensure adherence to the study day
      restrictions.

      On the day of the scan, they will only be allowed a small glass of water on waking. They will
      undergo a baseline fasting scan at 0900 hours (defined at t = -45 min time point), together
      with a fasting baseline blood sample. At 0925 hours, they will be asked to eat their test
      meal within a maximum time of 20 min so that at 0945 hours the subjects will undergo a first
      immediate postprandial scan (defined as t = 0 min). This will be followed with data
      collection (MRI, questionnaire data and blood samples) time points every 15 min for the first
      60 min and every 30 min up to 270 min.

      At each time point, the positioning of the subject, setup and data collection will take
      ~15min. After the first 60 min, at completion of data collection at each time-point, the
      volunteers will be kept sitting upright in a quiet lounge next to the scanner. At each time
      point, volunteers will fill a 100mm Visual Analogue Scale (VAS) symptoms questionnaire
      scoring their feeling of fullness, bloating, distension, abdominal pain/discomfort and
      nausea. The VAS anchors were from 'not' to 'extremely'. Participants will be given a meal at
      the end of the study.

      Participants will be then given a volume (750mls-1000mls) of contrast agent to drink (within
      45 minutes) and a further MRI scan (time=30 minutes) will be undertaken to quantify disease
      activity. Participants will be given a meal at the end of the study. This is not part of the
      research protocol.

      MRI scanning will be carried out supine on either a 1.5T or 3.0 T Philips Achieva MRI scanner
      (Philips Healthcare, Best, The Netherlands) depending on availability. Fasting and
      post-prandial plasma tests: On the morning of the test, a 10 ml fasting blood sample will be
      drawn in aprotonin/EDTA tubes (BD-361017, BD Diagnostics, Oxford). Samples will be measured
      every 15 min to 270 min. Samples will be centrifuged at 4000 rpm for 5 min and stored on ice.
      Measurement of plasma peptides: All EC peptides (GLP-1, PYY) will be analysed through ELISA
      techniques (Millipore, UK). Serum CCK will be measured by RIA (Euro Diagnostic Products,
      Sweden). Total EC plasma peptide response will be presented as per individual time points and
      compositely as area under the curve (AUC).
    

Intervention name(s): Test soup meal feeding intervention
Intervention type(s): Other
Intervention description(s): Cream of chicken soup (400g) (or mushroom for vegetarians) (Heinz, Wigan, UK) used as a test meal intervention. The nutrient content /100g is: energy (kcal) 51, protein (g) 1.5, carbohydrate (g) 4.7, fat (g) 2.93
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Motility