Location Specific Differences in Intestinal Brake Activation

Study Overview
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Brief Summary
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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. The researchers will investigate the effects of intraduodenal, intrajejunal and intralileal infusion of casein (protein) on ad libitum food intake, satiation and in vivo release of the gut satiety peptides CCK, PYY and GLP-1 and glucose and insulin.

Official Title
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The Effect of Intestinal Brake Activation at Different Locations in the Gut on Food Intake and Hormone Release

Conditions
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Ileal Brake, Satiety, Overweight, Obesity, Overeating

Intervention / Treatment
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* Other: placebo
* Other: Casein (in duodenum)
* Other: Casein (in jejunum)
* Other: Casein (in ileum)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria In order to be eligible to participate in this study, a subject must meet all of the following criteria: Based on medical history and previous examination, no gastrointestinal complaints can be defined. Age between 18 and 65 years. This study will include healthy adult subjects (male and female). Women must be taking contraceptives. BMI between 18 and 25 kg/m2) Weight stable over at least the last 6 months (≤5% weight change) Exclusion criteria A potential subject who meets any of the following criteria will be excluded from participation in this study: History of severe cardiovascular, respiratory, urogenital, gastrointestinal/ hepatic, hematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological/psychiatric diseases, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol. The severity of the disease (major interference with the execution of the experiment or potential influence on the study outcomes) will be decided by the principal investigator. Use of medication, including vitamin supplementation, except oral contraceptives, within 14 days prior to testing Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator), in the 180 days prior to the study Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and other surgery upon judgement of the principle investigator) Dieting (medically prescribed, vegetarian, diabetic, macrobiological, biological dynamic) Pregnancy, lactation Excessive alcohol consumption (>20 alcoholic consumptions per week) Smoking Blood donation within 3 months before the study period Self-admitted HIV-positive state Weight <60kg Evidence of casein or sucrose hypersensitivity Participation in any other study in which radiation was used, within 12 months before the study period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Tap water infusion in all three locations (duodenum, jejunum and ileum) | Other: placebo<br>* infusion of tap water in all regions (duodenum, jejunum and ileum)<br>|
| Experimental: Duodenum<br>Infusion of casein in duodenum | Other: Casein (in duodenum)<br>* infusion of protein in duodenum<br>|
| Experimental: Jejunum<br>Infusion of casein in jejunum | Other: Casein (in jejunum)<br>* infusion of protein in jejunum<br>|
| Experimental: Ileum<br>Infusion of casein in ileum | Other: Casein (in ileum)<br>* infusion of protein in ileum<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure ad libitum food intake at the end of the test day | Food intake measurement in kcal | 1 test day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VAS scores for hunger and satiety | Visual analogue scale for hunger and satiety in mm (0-100 mm scale) | 1 test day | 
| GI peptides | Measurement of GI peptide release during protein infusion (CCK, GLP-1, PYY, insulin and glucose) | 1 test day |