Reduced Appetite in Crohn's Disease: The Role of the Brain in the Control of Food Intake

University of Nottingham80 enrolled

Overview

Crohn's disease (CD) is becoming more common, specifically in the western world. One of the main features of this disease is weight loss and malnutrition. Although clinically common, these problems are not well understood. Loss of appetite and symptoms such as tummy aches and bloating are common causes for weight loss in this group of patients. This problem has a strong negative effect on the patients' quality of life and significantly increases the cost of treating CD. Enteroendocrine cells are nutrient sensors in the bowel that relay to the brain to control food intake. Recent evidence has showed that these cells increase in number in active CD and secrete more hormones that negatively affect appetite. The increased levels of these hormones should have an overall negative effect on the brain and thus decrease food intake, bloating, symptoms of sickness. All these symptoms lead to malnutrition. These are hypotheses that require further proof. Current technological advances in magnetic resonance imaging (MRI) has enabled the mapping of changes in activity in important areas in the brain that control food intake. The involvement of the brain in control of food intake is still not fully understood. This work will be the first step in the right direction to start targeting the problems of appetite, weight loss and a poor quality of life.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Crohn's Disease

Eligibility

Sex: ALLMin age: 16 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age 16-75 years 2. Ulceration seen at ileocolonoscopy, aiming for a simple endoscopic score for Crohn's disease (SES-CD) of 4-19, in the absence of stricturing disease or, 3. Intestinal inflammation or deep ulceration seen on CT or MR enterography, with the disease activity quantified via the MaRIA score or, 4. Faecal calprotectin of \>250µg/g 5. C-Reactive protein \>5mg/dl 6. Harvey-Bradshaw index score of 5-16 7. Body mass index (BMI) 18-35 8. As for HV participants, inclusion criteria 1 and 7 will apply. Exclusion Criteria: 1. Malignant disease 2. BMI \<18 and \>35 3. Significant cardiovascular or respiratory disease 4. Diabetes mellitus 5. Current Infection 6. Neurological or cognitive impairment; significant physical disability 7. Significant hepatic disease or renal failure 8. Abnormal blood results other than those explained by CD including bleeding diatheses (apart from in the case of HV where all unexplained blood results are an exclusion criteria) 9. Subjects currently participating in (or in the last three months) any other research project 10. pregnancy or breastfeeding or 11. if MRI is contraindicated (e.g. pacemaker). 12. Severe Crohn's disease where a delay in a change in medical treatment for 23 weeks would not be clinically advisable. 13. As for healthy volunteer participants all exclusion criteria apart from no.12.

Outcomes

Primary Outcomes

Changes in Blood Oxygenation Level Dependent (BOLD) response in the brain following a fatty acid test meal in Crohn's patients and healthy controls

Time frame: 3 years

Secondary Outcomes

Changes in arterial spin labeling measures of cerebral blood flow and changes in gut peptide levels following the fatty acid test meal.

The increase or decrease in BOLD signal of the brain following the fatty acid stimuli will be correlated to the gut peptide levels which are listed as follows: 1. CCK (pmol/ml) 2. GLP-1 (pM) 3. PYY (pg/ml) 4. Ghrelin (ng/ml)