Imaging the Effect of Experimental Stress on Small and Large Bowel Water During Fructose Absorption
Condition: Healthy
Study type: Interventional
Phase: Phase 4

Summary: 
      The investigators have been developing new, non-invasive magnetic resonance imaging (MRI)
      techniques to image the small bowel. Building on those studies the investigators want to
      study, in healthy volunteers, the effects of stress on the water content of the small bowel
      following ingestion of fructose. This is important because in Irritable Bowel Syndrome (IBS),
      there seems to be a strong association of stress and anxiety with the severity of the
      disease. Many IBS patients complain of food intolerances and recent studies have suggested
      that food with high content of fructose can worsen symptoms of IBS. The investigators will
      carry out a study in which the investigators will induce a moderate state of stress in
      healthy volunteers using an injection of corticotrophin release hormone, feed them a drink
      containing fructose and image their bowel at intervals using MRI. Improving our understanding
      of the effects of stress and fructose on small bowel physiology will help us to understand
      better some aspects of the symptoms such as bloating, altered bowel habit and abdominal
      discomfort, experienced by the IBS patients and to guide therapy. The investigators
      hypothesize that the effect of CRH will cause significant decrease in small bowel water
      content (SBWC) and a faster small bowel transit with increased malabsorption following
      consumption of fructose.
    

Detailed description: 
      A single centre, randomized cross over study consisting a screening visit and 2 test days
      which will be approximately 7 days apart. The participants will receive 1g unlabelled lactose
      ureide in a glass of water 3 times a day on the day before the study day to induce the enzyme
      activity in the colonic bacteria. The participants (20 healthy volunteers) will have a
      baseline scan in a 1.5T MRI scanner before having a small intravenous needle inserted into
      their forearm. Following this procedure, the participant will have another scan before being
      given either a saline (0.9% NaCl) or 100microgram of CRH intravenous injection. 40g of
      fructose and 500mg of labeled C-13 lactose ureide dissolved in water with pure lime juice as
      flavorant made up to 500mL will be given to the participants. They will then have a serial
      scanning of the abdomen at 30-60 minutes interval for 5 hours post prandially. Salivary
      cortisol will be collected after every MRI scans. Participants will also be asked to blow
      into the hydrogen breath machine and to fill in symptom questionnaire following each MRI
      scans. Further breath collections for orocaecal transit time will be collected initially
      every 10 minutes for the first hour and 15 mins until the end of the study day. Mouthwash
      will be used before initial breath test collection. This procedure will be repeated again on
      the 2nd test day with either a saline or 100microgram of CRH.
    

Intervention name(s): CRH; Placebo
Intervention type(s): Drug; Drug
Other intervention name(s): Generic name: Corticorelin trifluroacetate; Proprietary name: CRH Ferring; Normal Saline (0.9%)
Intervention MeSH terms: Corticotropin-Releasing Hormone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science