Eating Behaviour in Crohn's Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- Dietary Recalls (Calorific Intake)
研究概览
简要总结
Food intake is mainly controlled through interactions between the gut and brain (the homeostatic control) and through our environment, with food exposure, mood and past experiences (the hedonic control) playing a major role. The link between the gut and the brain is mainly controlled through enteroendocrine cells (EC). These cells in the bowel sense nutrients in the food and link with the brain to control how much we eat. They make a number of hormones that link with the brain to control one's eating habits.
Crohn's disease (CD) is an inflammatory disease of the bowel which can present with a number of symptoms including weight loss and loss of appetite. We thought some time ago that an increase in the number and function of these EC could play a central role. Since then we have carried out work which has shown that in CD these EC increase in number and produce more hormones after a meal. This finding could have a negative effect on food intake. This would be one explanation to the symptoms so commonly experienced by these patients.
In CD we thus feel that there might be an imbalance in the appetite control. We expect an increasingly sensitive gut to food intake and a subdued mood and perception to food reward and that this imbalance will lead to a decrease in food reward and consequently a decrease in food intake.
This study will be carried out using Healthy Volunteers and CD patients. We plan to measure food intake though telephone interviews and plan to analyse eating behaviour through 5 questionnaires.This study will help us to improve our understanding of what it is that controls food intake. This will be particularly important to patients with CD who routinely lose weight and appetite.
详细描述
STUDY BACKGROUND INFORMATION AND RATIONALE
Crohn's disease (CD) patients can present with a variety of luminal and extra-luminal symptoms but nutritional abnormalities are a very common but poorly studied [1] problem in this disease [2]. Apart from disease burden and repeated surgery, reduced appetite [3] and associated symptoms such as nausea undoubtedly contribute, with a major impact on quality of life.
Appetite and satiation, the processes by which a meal is terminated, involve complex interactions of homeostatic and hedonic factors. While the hypothalamus is central in the homeostatic control of food intake, other neural circuits integrate environmental and emotional cues to constitute the hedonic drive of appetite regulation. The homeostatic control of food intake is governed by the enteroendocrine-gut brain axis. Enteroendocrine cells (EC) play a pivotal role in orchestrating physiological functions in the gastrointestinal (GI) tract. Sensing the nutrient content of the lumen, they secrete multiple peptides and amines that control gut secretory and motor functions. Gut hormones act on vagal afferents in the GI tract, directly relaying to key central nervous system (CNS) nuclei that interface within the hypothalamus and other cortical areas to regulate food intake. CD patients with active small bowel inflammation show significant up-regulation of EC cells with an increase in ileal expression of chromogranin A [4, 5], glucagon-like peptide-1 (GLP-1) [4], key transcription factors in the stem cell to EC differentiation pathway [4] , plasma polypeptide YY (PYY) [3], cholecystokinin (CCK) [6] levels and a reduction in the key enzyme dipeptidyl peptidase-4 expression [7]. This increase in plasma peptide levels is associated with the symptoms of nausea and anorexia, with both symptoms, and tissue and plasma EC-peptide expression decreasing to normality in remission [3].
An increase in EC expression at the tissue and plasma level might affect appetite regulation through an increase in CNS signalling.
Fatty-acids infused in the gut, lead to a CCK-dependent increase in CNS activity in areas related to homeostatic control of feeding such as the brainstem, the pons, hypothalamus, cerebellum and the motor cortical areas [8]. Glucose has been shown to decrease the response in the upper hypothalamus [9], possibly via a GLP-1-mediated pathway [10]. Ghrelin and PYY have known homeostatic CNS signalling properties but play a hedonic role in the control of food intake [11]. In effect, the increase in plasma PYY and GLP-1 seen after Roux-en-Y gastric bypass surgery in obese subjects or after parenteral administration [12] is associated with a lower activation in brain-hedonic food responses and a healthier eating behaviour [13]. In CD, we expect a subdued reward value of food, but postulate that this would be aversive, and inappropriately impairing appetite and food intake.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 16 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •We will study a cohort of CD patients with active disease as defined by:
- •Age 16-75 years
- •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,
- •Intestinal inflammation or deep ulceration seen on CT or MR enterography, with the disease activity quantified via the MaRIA score or
- •Faecal calprotectin of >250µg/g or
- •C-Reactive protein >5mg/dl or,
- •Harvey-Bradshaw index score of 5-16
- •Body mass index (BMI) of 18-
- •For HV participants, inclusion criteria's 1 and 7 apply.
排除标准
- •Present or recent (within 12 weeks) corticosteroid usage
- •Malignant disease
- •BMI <18 or >
- •Significant cardiovascular or respiratory disease
- •Diabetes mellitus
- •Current Infection
- •Neurological or cognitive impairment; significant physical disability
- •Significant hepatic disease or renal failure
- •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) ,
- •Subjects currently participating in (or in the last three months) any other research project
- •pregnancy or breastfeeding or
- •Severe CD where a delay in a change in medical treatment for 1 weeks would not be clinically advisable
- •For HV participants, all exclusion criteria apply with the exception of criteria no.12
结局指标
主要结局
Dietary Recalls (Calorific Intake)
时间窗: Participants will be included in this study for 1 week
The primary endpoints for this study will be food intake as measured by one telephone-administered 24-h dietary recall. Total calorific intake will be calculated.
次要结局
- The Binge Eating Scale(Healthy volunteer participants will be included in this study for 1 week. Crohn's Disease participants will be included in the study until they are re-assessed in remission. A time limit of 12 months will be given.)
- The Power of Food Scale(Healthy volunteer participants will be included in this study for 1 week. Crohn's Disease participants will be included in the study until they are re-assessed in remission. A time limit of 12 months will be given.)
- Three Factor Eating Questionnaire (TFEQ) Restraint, Disinhibition and Hunger Subscales(Healthy volunteer participants will be included in this study for 1 week. Crohn's Disease participants will be included in the study until they are re-assessed in remission. A time limit of 12 months will be given.)
- The Control of Eating Questionnaire(Healthy volunteer participants will be included in this study for 1 week. Crohn's Disease participants will be included in the study until they are re-assessed in remission. A time limit of 12 months will be given.)
- The Dutch Eating Behaviour Questionnaire(Healthy volunteer participants will be included in this study for 1 week. Crohn's Disease participants will be included in the study until they are re-assessed in remission. A time limit of 12 months will be given.)