The Effect of Macronutrients on Satiety and Gut Hormone Responses

Study Overview
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Brief Summary
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This study is part of a research theme aiming at elucidating the physiological mechanisms of action of weight loss after gastric bypass surgery. The Roux-en-Y Gastric Bypass procedure induces pronounced and sustained weight loss, but the physiological mechanisms of action are not completely clear. Neither mechanical restriction of food intake nor malabsorption, are the main contributing factors. The enhanced postprandial responses of gut hormones (e.g. GLP-1 and PYY) which increase satiety as well as energy expenditure after surgery suggest a changed physiological set point for appetite and metabolism. Our hypothesis is that the intake of high quantity of protein in a microcapsule form would be able to reach the distal parts of the intestinal mucosa and stimulate maximum stimulation of the anorectic gut hormones. The higher functions of the brain will respond to these strong neuroendocrine signals by ensuing satiety and fullness.

Detailed Description
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Ten healthy volunteers, aged 18 to 65 years will be recruited. Each subject will be studied on six occasions one week apart. On each visit, a baseline serum sample will be drawn from each subject. In a randomized way all subjects will receive the following meals in their successive weekly visits: Option 1 High protein mixed meal in capsules that break down in the stomach, Option 2 High protein mixed meal in capsules that break down in the distal small bowel, Option 3 High fat mixed meal in capsules that break down in the stomach, Option 4 High fat mixed meal in capsules that break down in the distal small bowel, Option 5 High CHD mixed meal in capsules that break down in the stomach, Option 6 High CHD mixed meal in capsules that break down in the distal small bowel. On the same day, all subjects will be offered standard ad libitum meal to measure their food consumption. After 3 hours (i.e. at 12:00) another blood sample will be drawn. All subjects will be asked to rate their appetite on a Visual Analogue Scale (VAS). Upon VAS completion the subjects will be allowed to go home.

Official Title
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A Physiological Study on the Effect of Macronutrients Delivery to the Proximal and Distal Small Bowel on Satiety and Gut Hormone Responses

Conditions
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Eating Behavior

Intervention / Treatment
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* Dietary Supplement: Protein stomach
* Dietary Supplement: Protein distal small intestine
* Dietary Supplement: CHO stomach
* Dietary Supplement: CHO distal small intestine
* Dietary Supplement: Fat stomach
* Dietary Supplement: Fat distal small intestine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-65 years Normal fasting glucose Stable body weight for at least last three months BMI < 30 Kg/m2 Capacity to consent to participate Independently mobile Exclusion Criteria: Patients who meet any of the following criteria will be excluded: Pre-diabetes Diabetes Obesity Smoking Substance abuse Pregnancy Use of medications (except for oral contraceptives) Chronic medical or psychiatric illness Any significant abnormalities detected on physical examination, electrocardiography, or screening blood tests (measurement of complete blood count, electrolytes, fasting glucose, and liver function)

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 |
| --- | --- |
| Experimental: Protein stomach<br>Encapsulated protein released in the stomach | Dietary Supplement: Protein stomach<br>* encapsulated protein stomach<br>|
| Experimental: Protein distal small intestine<br>Encapsulated protein released in the distal small intestine | Dietary Supplement: Protein distal small intestine<br>* encapsulated protein distal small intestine<br>|
| Experimental: CHO stomach<br>Encapsulated CHO released in the stomach | Dietary Supplement: CHO stomach<br>* encapsulated CHO stomach<br>|
| Experimental: CHO distal small intestine<br>Encapsulated CHO released in the distal small intestine | Dietary Supplement: CHO distal small intestine<br>* encapsulated CHO distal small intestine<br>|
| Experimental: Fat stomach<br>Encapsulated Fat released in the stomach | Dietary Supplement: Fat stomach<br>* encapsulated Fat stomach<br>|
| Experimental: Fat distal small intestine<br>Encapsulated Fat released in the distal small intestine | Dietary Supplement: Fat distal small intestine<br>* encapsulated Fat distal small intestine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Effect of Proteins on the Secretion of Gut Hormones From Different Parts of the Gastrointestinal Tract | 3 hours AUC for different gut hormones (PYY) to determine the response to macronutrients in different release (stomach vs small intestine) locations. AUC for timepoints 0, 30min, 60min, 120min, 180min. | 3 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Intake (kj) of ad Libitum Lunch Meals to Assess Food Intake | Food intake as assessed with ad libitum lunch 3 hours after intervention | 3 hours | 
| Visual Analogue Scale Ratings of Hunger | Visual Analogue Scale ratings of hunger at 180 min (before the meal). The scale is 10cm line with two anchors at each end. Scores are recorded by making a handwritten mark that represents a continuum between not hungry at all and Extremly hungry. The score of 0 represents least hunger. The score of 10 represent extreme hunger. | 180min |