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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
20
Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham
Nottingham, United Kingdom
NIHR Nottingham Digestive Diseases Biomedical Research Unit
Nottingham, United Kingdom
Effect of CRF on area under curve volume versus time curve for small bowel water
Magnetic Resonance Imaging will be used to measure small bowel water at 30-60 minutes intervals for a total of 430 minutes
Time frame: 430 minutes in total
Effect of CRF on increase in volume of gas in colon at 255 minutes
Magnetic resonance imaging will be used to assess colonic gas at 255 minute time point
Time frame: 15 minutes
Gastric Emptying
Magnetic Resonance Imaging will be used to assess gastric emptying at 30-60 minute intervals for a total of 430 minutes
Time frame: 430 minutes
small bowel transit time using lactose C-13 ureide
Unlabelled lactose ureide 1g x3/day will be given 24 hours prior to study day. They will then be given 500mg 13C labelled lactose ureide on the study day and breath collections every 10 minutes initially for 1 hour and every 15 minute for subsequent hours
Time frame: 430 minutes
Ascending colon volume
Ascending colon volumes will be assessed using the Magnetic Resonance Imaging technique at 30-60 minute intervals
Time frame: 430 minutes
Volume of gas in colon
Volume of gas in colon will be assessed using the Magnetic Resonance Imaging technique at 30-60 minute intervals
Time frame: 430 minutes
salivary cortisol level versus small bowel water content
Saliva samples will be collected at the 30-60 minute intervals (as per the magnetic resonance imaging scans for small bowel water content)
Time frame: 430 minutes
Correlating symptom scores on the study day and Bristol Stool diary
Stool diary to be collected for a week
Time frame: 7 days
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