Brain Activity and Hormonal Changes During Food Administration
Condition: Appetite Regulation
Study type: Interventional

Summary: 
      The amount and kind of food which is ingested influences the regulation of meal size. Neural
      signals from the gastrointestinal tract travel via the vagus nerve to the brainstem and
      thalamus, which projects to the rest of the brain, in particular the hypothalamus, amygdala
      and primary sensory cortices. In neuroimaging studies in which the stomach was distended with
      a gastric balloon activation was observed in the right insula, left posterior amygdala, left
      posterior insula, left inferior frontal gyrus and anterior cingulate cortex. So far, no study
      has examined the effects of the ingestion or infusion of a food on the brain. In addition to
      neural signals, hormonal signals are important for meal termination. Hormones like insulin,
      ghrelin and cholecystokinin interact with gastric as well as sensory signals in the process
      of satiation, which ultimately leads to meal termination. The aim of this study is to
      investigate the interaction between food administration, hormone responses and brain
      responses. To this end an oral or intra-gastric load will be administered while measuring
      brain activity (functional magnetic resonance imaging) and hormone concentrations. Subjects
      will participate in one trainings session and in three functional magnetic resonance imaging
      (fMRI) sessions (35-min fMRI scan). A training session will take 40-minutes and consists of
      placing a naso-gastric tube and ingesting 500 ml of chocolate milk orally. The fMRI sessions
      will consist of three conditions: in condition one (A) 500ml of chocolate milk will be
      administrated orally. In condition two (B) and three (C) an intra-gastric load of 500 ml is
      administrated.
    

Detailed description: 
      Study procedures

        1. Screening: Before inclusion in the study, potential subjects will complete a screening
           questionnaire Subjects will then be informed about their eligibility. Also the procedure
           and risks will be explained. If they decide to participate, they will fill in and sign
           the standard MRI-screening form and the informed consent form. Also a training session
           date will be planed.

        2. Training session: When subjects want to participate and match to the criteria a training
           session will be planned. During this training session a naso-gastric tube will be
           inserted by a qualified nurse (according to the "maagsonde-protocol" UMC Utrecht). After
           insertion of the tube subjects rest to allow water used to assist insertion of the tube
           to leave the stomach and to become comfortable with the tube. During this insertion the
           nurse and the subject can see if a subject can handle the naso-gastric tube and can or
           will participate in the study. Subjects will rate hunger, fullness, thirst, desire to
           eat, prospective consumption, nauseous, and anxiety on a VAS scale. To simulate the
           position in the MR scanner, subjects will be asked to lie down on a doctors table. A
           towel will be placed under need there right side, in this way the stomach will be more
           in the position when standing/sitting, this is to simulate normal gastric filling. A
           tube will be placed between the teeth of the subject (like a straw) after which an oral
           load of 500 ml will be ingested through the tube in the month. This ingestion will be
           driven by a pomp (100ml/min), which simulates a sip systematically. First 200 ml will be
           ingested, then there will be a pause of 30 seconds, second the next 150 ml will be
           pumped, following again a 30 second rest period, then the last 150 ml will be ingested.
           The subjects know the rate and speed of the sips and can stop the pomp on command when
           necessary. The subject will also hear a tone just before the sip is ingested. Here a
           subject learns to drink with a naso-gastric tube placed and when lying down. After
           ingestion the subjects will fill in the same questionnaire again. The naso-gastric tube
           will be removed after the rating. This training session will take about 40 minutes.

        3. Assessments and procedures on the study days: All subjects will be asked to arrive in
           the morning after an overnight fast of at least 10 hours. The evening before the scan
           subjects will be ask to eat a standardized meal given by the researchers (AH kant &
           klaar). An appetite questionnaire will be filled in (hunger, fullness, thirst, desire to
           eat, quantity to eat, desire to eat something sweet or savory, nauseous, and anxiety).
           An intravenous cannula will be placed by a qualified person. Next, the naso-gastric tube
           will be placed (same procedure as training session). After the subject has been placed
           in the scanner (as in the training session with a towel under need there right side);
           one blood draw will be done for baseline measurements (e.g. glucose, insulin,
           cholecystokinin and ghrelin for every time point). The appetite questionnaire will be
           filled in again in the scanner. A reference and anatomic scan will be done. Now the fmri
           session begins; after five minutes of baseline scanning, food administration will start
           (t = 0). This consists of administration of the intra gastric load through the
           naso-gastric tube (caloric or non-caloric) or of ingestion of the caloric load through a
           tube (oral). Blood will be drawn at t = 2.5, t = 5, t = 10, t = 15 and at t = 30 min.
           Before every blood sample subjects will give fullness and nausea ratings. One of the
           researchers will stand next to the subject/scanner during the whole experiment. If
           aspiration occurs a researcher will be there to help immediately. The researchers also
           make sure a subject knows how to get out of the scanner as quick as possible if
           aspiration occurs. At t = 30 min the subject will be taken out the scanner and fill in
           the appetite questionnaire. The naso-gastric tube and intravenous cannula will be
           removed. Subsequently subjects will be provided with an ad libitum breakfast buffet at t
           = 45 min. Food weight and macro-nutrient intake will be recorded. After breakfast the
           appetite questionnaire is filled in once more.

        4. Blood sampling and storage: On the study day, a 10 ml blood sample will be drawn by
           certified experienced medical personnel. Blood samples will be put on ice immediately
           and then centrifuged at 1730 × g for 10 min at 4 ˚C. Blood material from the collection
           tubes will be split into two portions and stored, one portion for the analyses and one
           portion as a backup. Blood serum will be stored at -80 ˚C at the Rudolf Magnus Institute
           until sample collection is complete. Only RMI laboratory personnel and the investigators
           will have access to the samples. Blood samples will be coded as follows: P01, P02, etc.
           The key to this code will only be known by the principal and medical investigators and
           not by the personnel performing the blood analyses. Samples will be kept for 10 years
           and then destroyed.

        5. Naso-gastric tube: A qualified nurse will place the naso-gastric tube. The placement
           will go according to the 'maagsonde -protocol' (UMC Utrecht). After insertion of the
           tube subjects rest to allow water used to assist insertion of the tube to leave the
           stomach and to become comfortable with the tube.

        6. Withdrawal of individual subjects: Subjects can leave the study at any time for any
           reason if they wish to do so without any consequences. The investigator can decide to
           withdraw a subject from the study for urgent medical reasons. Each subject who does not
           complete the study for any reason will have a post-study screening by the end of the
           particular study day to ensure that the drop-out is not the result of a structural
           problem. Data of subjects who withdrew prematurely will be used for statistical
           analyses, as far as possible.

        7. Replacement of individual subjects after withdrawal: In case subjects withdraw during
           the study (fMRI sessions), they will not be replaced. If a subject decides not to
           participate during the training session a new subject will be recruited.

        8. Follow-up of subjects withdrawn from treatment: Subjects who withdraw from the study
           will not be followed up, unless they withdraw because of an adverse event.

        9. Post-study screening: Subjects will be asked how they experienced the study procedures.
           This information, if the subject is willing to share it, will be used to evaluate (the
           burden of) the study protocol.
    

Intervention name(s): Water with guar gum - Non Caloric; Chocolate milk - Oral Caloric; Chocolate milk - Intra Gastric Caloric
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Infusion 500 ml of water with 3 gram of guar gum through a naso-gastric tube directly into stomach during a fMRI scan.; Ingestion of 500 ml of commercially available chocolate milk (Per 100mL; energy content of 354 kJ, 84 kcal, 3.5 g proteins, 12 g mono and disaccharide, 2.5 fat g, 0.5 g fibers) through a tube in the mouth during a fmri scan.; Infusion of 500 ml of commercially available chocolate milk (Per 100mL; energy content of 354 kJ, 84 kcal, 3.5 g proteins, 12 g mono and disaccharide, 2.5 fat g, 0.5 g fibers) through a naso-gastric tube directly into stomach during a fMRI scan.
Other intervention name(s): Guar gum has the E number E412 and is allowed in the EU; Chocomel®, FrieslandCampina, Ede, the Netherlands; Chocomel®, FrieslandCampina, Ede, the Netherlands
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Satiation; Brain activation; Gut peptides