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Eating Behaviour in Crohn's Disease
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.
Visão geral do estudo
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Descrição detalhada
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.
We hypothesize that in CD and small bowel inflammation we will observe a change in eating behaviour with loss of hedonic drives and food reward responses and an accentuated homeostatic response.
STUDY OBJECTIVES AND PURPOSE
PURPOSE The overall purpose of the study is to quantify food intake in patients with active Crohn's disease and compare it to when they are in remission and to healthy age, BMI and gender-matched healthy cohort of volunteers. We will quantify eating behaviour traits in the same patient cohort when in active disease and repeat when in remission. These data will be compared to that of healthy volunteers.
PRIMARY OBJECTIVE The primary objective is to quantify food intake in patients with active CD and compare this to HV.
SECONDARY OBJECTIVES The secondary objectives of this study are to a) quantify food intake in patients with active CD and compare that when in inactive disease. b) quantify changes in appetite and eating behaviour in patients with active CD and compare these to those in HV and inactive CD as measured by the appetite-related questionnaires
Tipo de estudo
Inscrição (Real)
Contactos e Locais
Locais de estudo
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Nottinghamshire
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Nottingham, Nottinghamshire, Reino Unido, NG7 2UH
- Queens Medical Centre
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Método de amostragem
População do estudo
Recruitment
The chief investigator is a specialist in Inflammatory Bowel disease and also an associate professor of gastroenterology at the University of Nottingham and Nottingham University Hospital which is a tertiary-level care academic institution covering a population of approximately 1 million people for secondary-level care and 4.5 million people for tertiary-level care. Collectively we manage approximately 4000 IBD patients.
Participants shall be recruited from two sources:
- Crohn's Disease patients from clinic.
- Crohns Disease patients and Healthy Volunteers via the study flyer and social media.
Descrição
Inclusion Criteria:
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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 18-30.
For HV participants, inclusion criteria's 1 and 7 apply.
Exclusion Criteria:
- Present or recent (within 12 weeks) corticosteroid usage
- Malignant disease
- BMI <18 or >30.
- 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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Modelos de observação: Coorte
- Perspectivas de Tempo: Prospectivo
Coortes e Intervenções
Grupo / Coorte |
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Crohn's Disease Patients
Patients with a diagnosis of Crohn's disease fitting the studies inclusion & exclusion criteria.
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Healthy Volunteers
For healthy volunteers the studies exclusion criteria apply.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Dietary Recalls (Calorific Intake)
Prazo: Participants will be included in this study for 1 week
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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.
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Participants will be included in this study for 1 week
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Three Factor Eating Questionnaire (TFEQ) Restraint, Disinhibition and Hunger Subscales
Prazo: 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.
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The TFEQ contains 51 items and measures three dimensions of human eating behaviour: Cognitive Restraint of Eating [I], Disinhibition [II], and Hunger [III].
Each item scores either 0 or 1 point.
The minimum score for factors I, II. and III is therefore 0, with the pos- sible maximum scores being 21, 16, and 14 respectively.
High scores mean worse outcome.
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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.
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The Binge Eating Scale
Prazo: 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.
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The BES is a 16-item questionnaire that assesses the severity of binge eating tendencies.
Eight questions describe the behavioural mani- festations of binge eating behaviour and eight describe the feelings and cognitions associated with binge eating.
Scores are summed to produce a total score ranging from 0 to 46.
Cut-off points have previously been reported denoting mild [≤17], moderate [18-26], and severe [≥27] binge eating behaviours.
High score means worse outcome
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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.
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The Power of Food Scale
Prazo: 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.
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The PFS is a 15-item questionnaire reflecting the psychological influence of the food environment.
It measures appetite for, rather than consumption of, palatable foods and may be a useful measure of the hedonic impact of food environments replete with highly palatable foods.
Items are grouped into three domains according to food proximity; food available but not physically present; food present but not tasted; and food tasted but not consumed.
High scores mean worse outcome
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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.
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The Dutch Eating Behaviour Questionnaire
Prazo: 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.
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The 33-item DEBQ assesses different eating styles that may contribute to weight gain: emotional eating, external eating, and restraint.
'Emotional eating' occurs in response to emotional arousal states such as fear, anger, or anxiety; 'external eating' occurs in response to external food cues such as sight and smell of food; and 'restraint eating' is overeating after a period of slimming when the cognitive resolve to diet is abandoned.
High score means worse outcome
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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.
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The Control of Eating Questionnaire
Prazo: 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.
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The CoEQ is a 21-item questionnaire designed to assess the severity and type of food cravings experienced over the previous 7 days.
The CoEQ has four subscales: Craving Control, Craving for Savoury, Craving for Sweet, and Positive Mood.
Items on the CoEQ are assessed by 100-mm visual analogue scales [VAS], with items relating to each subscale being averaged to create a final score.
High positive mood is better outcome
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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.
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Gordon W Moran, University of Nottingham
Publicações e links úteis
Publicações Gerais
- Bryant RV, Trott MJ, Bartholomeusz FD, Andrews JM. Systematic review: body composition in adults with inflammatory bowel disease. Aliment Pharmacol Ther. 2013 Aug;38(3):213-25. doi: 10.1111/apt.12372. Epub 2013 Jun 14.
- Lochs H, Dejong C, Hammarqvist F, Hebuterne X, Leon-Sanz M, Schutz T, van Gemert W, van Gossum A, Valentini L; DGEM (German Society for Nutritional Medicine), Lubke H, Bischoff S, Engelmann N, Thul P; ESPEN (European Society for Parenteral and Enteral Nutrition). ESPEN Guidelines on Enteral Nutrition: Gastroenterology. Clin Nutr. 2006 Apr;25(2):260-74. doi: 10.1016/j.clnu.2006.01.007. Epub 2006 May 15.
- Moran GW, Leslie FC, McLaughlin JT. Crohn's disease affecting the small bowel is associated with reduced appetite and elevated levels of circulating gut peptides. Clin Nutr. 2013 Jun;32(3):404-11. doi: 10.1016/j.clnu.2012.08.024. Epub 2012 Sep 3.
- Moran GW, Pennock J, McLaughlin JT. Enteroendocrine cells in terminal ileal Crohn's disease. J Crohns Colitis. 2012 Oct;6(9):871-80. doi: 10.1016/j.crohns.2012.01.013. Epub 2012 Mar 3.
- Moran GW, McLaughlin JT. Plasma chromogranin A in patients with inflammatory bowel disease: a possible explanation. Inflamm Bowel Dis. 2010 Jun;16(6):914-5. doi: 10.1002/ibd.21096. No abstract available.
- Keller J, Beglinger C, Holst JJ, Andresen V, Layer P. Mechanisms of gastric emptying disturbances in chronic and acute inflammation of the distal gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol. 2009 Nov;297(5):G861-8. doi: 10.1152/ajpgi.00145.2009.
- Moran GW, O'Neill C, Padfield P, McLaughlin JT. Dipeptidyl peptidase-4 expression is reduced in Crohn's disease. Regul Pept. 2012 Aug 20;177(1-3):40-5. doi: 10.1016/j.regpep.2012.04.006. Epub 2012 May 2.
- Lassman DJ, McKie S, Gregory LJ, Lal S, D'Amato M, Steele I, Varro A, Dockray GJ, Williams SC, Thompson DG. Defining the role of cholecystokinin in the lipid-induced human brain activation matrix. Gastroenterology. 2010 Apr;138(4):1514-24. doi: 10.1053/j.gastro.2009.12.060. Epub 2010 Jan 18.
- Smeets PA, de Graaf C, Stafleu A, van Osch MJ, van der Grond J. Functional magnetic resonance imaging of human hypothalamic responses to sweet taste and calories. Am J Clin Nutr. 2005 Nov;82(5):1011-6. doi: 10.1093/ajcn/82.5.1011.
- Pannacciulli N, Le DS, Salbe AD, Chen K, Reiman EM, Tataranni PA, Krakoff J. Postprandial glucagon-like peptide-1 (GLP-1) response is positively associated with changes in neuronal activity of brain areas implicated in satiety and food intake regulation in humans. Neuroimage. 2007 Apr 1;35(2):511-7. doi: 10.1016/j.neuroimage.2006.12.035. Epub 2007 Jan 18.
- Batterham RL, ffytche DH, Rosenthal JM, Zelaya FO, Barker GJ, Withers DJ, Williams SC. PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans. Nature. 2007 Nov 1;450(7166):106-9. doi: 10.1038/nature06212. Epub 2007 Oct 14.
- De Silva A, Salem V, Long CJ, Makwana A, Newbould RD, Rabiner EA, Ghatei MA, Bloom SR, Matthews PM, Beaver JD, Dhillo WS. The gut hormones PYY 3-36 and GLP-1 7-36 amide reduce food intake and modulate brain activity in appetite centers in humans. Cell Metab. 2011 Nov 2;14(5):700-6. doi: 10.1016/j.cmet.2011.09.010. Epub 2011 Oct 13.
- Scholtz S, Miras AD, Chhina N, Prechtl CG, Sleeth ML, Daud NM, Ismail NA, Durighel G, Ahmed AR, Olbers T, Vincent RP, Alaghband-Zadeh J, Ghatei MA, Waldman AD, Frost GS, Bell JD, le Roux CW, Goldstone AP. Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding. Gut. 2014 Jun;63(6):891-902. doi: 10.1136/gutjnl-2013-305008. Epub 2013 Aug 20.
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- 15005
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