Eating Behaviour in Crohn's Disease
Condition: Crohn's Disease
MeSH terms: Crohn Disease
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        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:

          1. Crohn's Disease patients from clinic.

          2. Crohns Disease patients and Healthy Volunteers via the study flyer and social media.