Intestinal Glucagon-like Peptide-1 (GLP-1) and the Physiological Role in Eating in Humans

Study Overview
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Brief Summary
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The aim is to further establish a physiological role for GLP-1 as an endogenous satiety signal by examining the effect of the specific GLP-1 receptor antagonist exendin (9-39) on appetite and food intake in healthy male subjects.

Detailed Description
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Understanding the exact mechanisms by which GLP-1 inhibits eating can be crucial in order to convert its anorectic action into useful, safe and effective drugs. So far, it is however not clear to what extent GLP-1 is a hormonal regulator of eating or whether the observed effects are rather a pharmacological phenomenon. By applying classical algorithms from endocrinology several criteria must be fulfilled before a hormone can be considered an endogenous physiological satiety signal. One is that exogenous administration of a selective antagonist should prevent the eating-inhibitory effect of GLP-1. At present, cholecystokinin (CCK) is the only peptide in humans identified to fit these criteria. For intestinal GLP-1, it has not been investigated whether a specific GLP-1 receptor antagonist can block the eating-inhibitory effect in humans. The availability of a specific GLP-1 receptor antagonist, exendin (9-39), now makes it possible to further investigate this pathway. Exendin (9-39), is a powerful tool available for human use to characterize of endogenous GLP-1 as a physiological regulator of different biological functions. The molecule has been used to document that endogenous GLP-1 is an important incretin hormone and a regulator of antro-pyloro-duodenal motility. The role of endogenous GLP-1 in regulating food intake and appetite has, however, not been investigated before.

Official Title
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Intestinal Glucagon-like Peptide-1 (GLP-1) and the Physiological Role in Eating in Humans

Conditions
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Appetite and General Nutritional Disorders

Intervention / Treatment
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* Dietary Supplement: Saline
* Drug: Exendin 9-39
* Dietary Supplement: Saline
* Drug: Exendin(9-39) plus ID nutrient


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subject with a BMI of 19-25 m2/kg Stable body weight for at least three months Normal eating habits Age between 18 and 45 years Sufficient understanding of the German language Subjects understand the procedures and the risks associated with the study Participants must be willing to adhere to the protocol and sign the consent form Exclusion Criteria: Participation in another clinical trial (currently or within the last 30 days) Smoking Substance abuse Regular intake of medications (except for oral contraceptives) Chronic or acute medical condition including clinically relevant abnormality in physical exam or laboratory values History of gastrointestinal disorders Food allergies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: iv saline, intraduodenal saline<br>intravenous infusion of saline plus intraduodenal administration of saline | Dietary Supplement: Saline<br>* Intravenous saline infusion and intraduodenal administration of saline via feeding tube<br>|
| Active Comparator: IV exendin(9-39) plus intraduodenal (ID) saline<br>intravenous infusion of exendin(9-39) plus intraduodenal administration of saline | Drug: Exendin 9-39<br>* IV exendin(9-39) infusion and intraduodenal administration of saline via feeding tube<br>|
| Placebo Comparator: IV saline, intraduodenal nutrient<br>intravenous infusion of saline plus intraduodenal administration of nutrient | Dietary Supplement: Saline<br>* IV saline infusion and intraduodenal administration of nutrients<br>|
| Active Comparator: Exendin(9-39) plus ID nutrient<br>Exendin(9-39) as intravenous infusion plus intraduodenal nutrient administration | Drug: Exendin(9-39) plus ID nutrient<br>* Exendin(9-39) as intravenous infusion plus intraduodenal nutrient administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of exendin(9-39)on total calorie intake |  | 60 min test meal | 
| Effect of exendin(9-39) on total fluid intake |  | 60 min test meal | 
| Effect of exendin(9-39)on meal duration during an ad libitum test meal. |  | 60 min test meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of exendin(9-39)on plasma concentration of glucose |  | 4 hours blood sampling | 
| Effect of exendin(9-39)on plasma concentration of insulin. |  | 4 hours blood sampling | 
| Effect of exendin(9-39)on plasma concentration of glucagon. |  | 4 hours blood sampling | 
| Effect of exendin(9-39)on plasma concentration of GLP-1. |  | 4 hours blood sampling | 
| Effect of exendin(9-39)on plasma concentration of peptide tyrosine tyrosine (PYY). |  | 4 hours blood sampling | 
| Effect of exendin(9-39)on plasma concentration of CCK. |  | 4 hours blood sampling | 
| Effect of exendin(9-39)on plasma concentration of ghrelin. |  | 4 hours blood sampling | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GLP-1, satiation peptides, food intake