Reduced Intestinal Motility in Inflammatory Crohn's Disease - Optimisation Studies in Healthy Volunteers
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Nottingham
- Enrollment
- 15
- Locations
- 2
- Primary Endpoint
- Small bowel motility
Study Overview
Brief 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.
Before studying the Crohn's patients it is necessary to run a set of pilot experiments in healthy volunteers using a test meal and subsequent MRI imaging to look at the motion of the gut. This validation stage of the methodology is essential before embarking in more detailed studies in the patients.
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, intestinal motility and whole gut transit.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Body Mass Index (BMI): 18-30 Kg/m2
Exclusion Criteria
- •Patients with a history of inflammatory bowel disease.
- •A history of bowel resections or any gastric surgery.
- •History of pancreatic insufficiency, thyroid disease or/and diabetes.
- •Protein-pump inhibitor usage or any medication that affects gastric emptying or small bowel transit.
- •Any potential participants scoring very highly on the depression scale questionnaire.
- •Standard MRI exclusion criteria (e.g. pacemaker).
- •Malignant disease
- •Stricturing or penetrating disease
- •Smoking history
- •History of bowel resections or any gastric surgery
- •Significant cardiovascular or respiratory disease
- •Current Infection
- •Neurological or cognitive impairment
- •Significant physical disability
- •Significant hepatic disease or renal failure
- •Subjects currently (or in the last three months) participating in another research project
- •pregnancy or breastfeeding
Outcomes
Primary Outcomes
Small bowel motility
Time Frame: From fasting baseline to 270 min postprandially
MRI small bowel motility index (arbitrary units)
Secondary Outcomes
- Gastric volumes(From fasting baseline to 150 min postprandially)
- Satiety(From fasting baseline to 270 min postprandially)
- Plasma GLP-1(From fasting baseline to 270 min postprandially)
- Whole gut transit(24 hours after ingestion of the MRI transit capsules)
- Plasma PYY(From fasting baseline to 270 min postprandially)
- Plasma CCK(From fasting baseline to 270 min postprandially)
- Gall bladder contraction(From fasting baseline to 60 min postprandially)
- Small bowel water content(From fasting baseline to 270 min postprandially)