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

Condition(s) targeted: Appetite and General Nutritional Disorders

Intervention: Saline (Dietary Supplement); Exendin 9-39 (Drug); Saline (Dietary Supplement); Exendin(9-39) plus ID nutrient (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: University Hospital, Basel, Switzerland

Official(s) and/or principal investigator(s):
Christoph Beglinger, MD, Principal Investigator, Affiliation: University Hospital Basel, Phase 1 Research Unit, Basel Switzerland

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Primary outcome:

Effect of exendin(9-39)on total calorie intake

Effect of exendin(9-39) on total fluid intake

Effect of exendin(9-39)on meal duration during an ad libitum test meal.

Secondary outcome:

Effect of exendin(9-39)on plasma concentration of glucose

Effect of exendin(9-39)on plasma concentration of insulin.

Effect of exendin(9-39)on plasma concentration of glucagon.

Effect of exendin(9-39)on plasma concentration of GLP-1.

Effect of exendin(9-39)on plasma concentration of peptide tyrosine tyrosine (PYY).

Effect of exendin(9-39)on plasma concentration of CCK.

Effect of exendin(9-39)on plasma concentration of ghrelin.

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.

Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Male.

Criteria:

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

University Hospital Basel, Phase 1 Research Unit, Basel, Switzerland

Starting date: November 2011
Last updated: July 11, 2013