The effect of intestinal brake activation at different locations in the gut on food intake and hormone release

Rationale: The appearance of intact macronutrients in the small intestine can
result in the activation of an intestinal brake; a negative feedback mechanism
from different parts of the intestine to the stomach, the small intestine and
to the central nervous system. These processes inhibit food processing,
appetite sensations and food intake, and furthermore they increase feelings of
satiety and satiation. We will investigate the effects of intraduodenal,
intrajejunal and intralileal infusion of casein (protein) and sucrose
(carbohydrate) on ad libitum food intake, satiation and in vivo release of the
gut satiety peptides CCK and GLP-1.

Study A:
Aim: To investigate the location specific differences (duodenum, jejunum and
ileum) of casein infusion on ad libitum food intake, satiety scores and the
release of gastrointestinal peptides , associated with food intake and satiety
(CCK, GLP-1 and PYY).
Hypothesis: We hypothesize that casein, when being infused into the duodenum
and jejunum, induces a decrease in ad libitum meal intake to the same extent
compared to infusion into the ileum.
Primary objective: To investigate the effect of targeted infusion of casein at
different locations in the small intestine on ad libitum food intake
Secondary Objective(s):
1. To investigate the effect of infusion of casein into different intestinal
locations (duodenum, jejunum and ileum) on satiety and satiation.
2. To assess the effect of infusion of casein at different intestinal locations
(duodenum, jejunum and ileum) on gastrointestinal peptide release.

Study B
Aim: To investigate location specific differences (duodenum, jejunum and ileum)
of targeted sucrose infusion on ad libitum food intake, satiety scores and the
release of gastrointestinal peptides associated with food intake and satiety
(CCK, GLP-1 and PYY).
Hypothesis: We hypothesize that sucrose, when being infused into the duodenum
and jejunum, induces a decrease in ad libitum meal intake to the same extent
compared to infusion into the ileum.
Primary objective: To investigate the effect of targeted infusion of sucrose at
different locations in the small intestine on ad libitum food intake
Secondary Objective(s):
1. To investigate the effect of infusion of sucrose into different intestinal
locations (duodenum, jejunum and ileum) on satiety and satiation.
2. To assess the effect of infusion of sucrose into different intestinal
locations (duodenum, jejunum and ileum) on gastrointestinal peptide release.
3. Compare whether differences in food intake, satiety and peptide release
related to targeted delivery of a stimulus are related to the type of stimulus
(casein vs sucrose)

Randomized, double-blind cross-over study. Substudy A: infusion of casein.
Substudy B: infusion of sucrose.

Infusing casein or sucrose in the small intestine

Blood sampling: on each test day (test day 1-4), after the positioning of the
nasoileal catheter by fluoroscopy, a flexible intravenous cannula (Biovalve
1,0mm) is inserted into an antecubital vein in the fore-arm for blood sampling.
Per time point 8mL of blood is drawn, totalling 72mL per test day (with a total
of 288mL for the 4 test days). After collection (immediately after collection
DPP-IV inhibitor will be added to the tube), K2EDTA tubes will be centrifuged
at 2500 rpm for 10 min at 4°C. The supernatant will be collected and this will
be centrifuged again at 4000 rpm for 10 min at 4°C. Plasma will be collected in
1-mL aliquots and stored at -80°C until analysis. During blood sampling, the
volunteers will remain seated in a comfortable chair, with an adjustable back.
No side effects are expected when sampling blood in this manner.
VAS scores for satiety and GI symptoms Scores for satiety feelings (e.g.,
satiety, fullness, hunger, prospective feeding, desire to eat, desire to snack)
and gastrointestinal symptoms (burning, bloating, belching, cramps, colics,
warm sensation, sensation of abdominal fullness, nausea and pain) will be
measured using Visual Analogue Scales (VAS, 0 to 100 mm) anchored at the low
end with the most negative or lowest intensity feelings (e.g., extremely
unpleasant, not at all), and with opposing terms at the high end (e.g.,
extremely pleasant, very high, extreme). Volunteers will be asked to indicate
on a line which place on the scale best reflects their feeling at that moment.
The scoring forms will be collected immediately so that they cannot be used as
a reference for later scorings.
Catheter placing and fluoroscopy: The subjects will perceive mild discomfort
during the placement of the catheter. Each test week starts with inserting a
nasoileal tube. The radiation exposure during the positioning of the feeding
tube is minimal (0.05 mSv). The total exposure to radiation (during all test
days) will be approximately 0.20 mSv (0.05 mSv x 4) , which equals the
radiation, which is received during 2 return flight from Amsterdam to Sydney in
an aeroplane at a 4-km altitude (www.nrg-nl.com). Since the catheter will be in
situ for 4 days and this can result in minor discomfort. Subjects can, at any
time, come in contact with the investigator if any problems occur. All
participants are healthy volunteers and we don't expect any health benefits or
disadvantages.