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

Phase 1

Completed

• Conditions: Appetite and General Nutritional Disorders
• Interventions: Dietary Supplement: Saline; Drug: Exendin 9-39; Drug: Exendin(9-39) plus ID nutrient

• Registration Number: NCT01900340
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

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

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.

Study Timeline

• Study Start: 2011-11
• Study First Submitted: 2012-04-03
• Primary Completion: 2012-12
• Study Completion: 2012-12
• Status Verified: 2013-07
• Study First Submitted QC: 2013-07-11
• Last Update Submitted: 2013-07-11
• Study First Posted: 2013-07-16
• Last Update Posted: 2013-07-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 12

Inclusion Criteria

1. Healthy male subject with a BMI of 19-25 m2/kg
2. Stable body weight for at least three months
3. Normal eating habits
4. Age between 18 and 45 years
5. Sufficient understanding of the German language
6. Subjects understand the procedures and the risks associated with the study
7. Participants must be willing to adhere to the protocol and sign the consent form

Exclusion Criteria

1. Participation in another clinical trial (currently or within the last 30 days)
2. Smoking
3. Substance abuse
4. Regular intake of medications (except for oral contraceptives)
5. Chronic or acute medical condition including clinically relevant abnormality in physical exam or laboratory values
6. History of gastrointestinal disorders
7. Food allergies

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
IV saline, intraduodenal nutrient	Saline	intravenous infusion of saline plus intraduodenal administration of nutrient
iv saline, intraduodenal saline	Saline	intravenous infusion of saline plus intraduodenal administration of saline
IV exendin(9-39) plus intraduodenal (ID) saline	Exendin 9-39	intravenous infusion of exendin(9-39) plus intraduodenal administration of saline
Exendin(9-39) plus ID nutrient	Exendin(9-39) plus ID nutrient	Exendin(9-39) as intravenous infusion plus intraduodenal nutrient administration

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

University Hospital Basel, Phase 1 Research Unit; 🇨🇭 Basel, Switzerland