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

University Hospital Basel

Status and phase: Completed; Phase 1

Conditions: Appetite and General Nutritional Disorders

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

Study type: Interventional

Funder types: Other

Identifiers

NCT01900340

EKBB 25/11

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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12 participants in 4 patient groups, including a placebo group

iv saline, intraduodenal saline

Placebo Comparator group

Description:

intravenous infusion of saline plus intraduodenal administration of saline

Treatment:

Dietary Supplement: Saline

Dietary Supplement: Saline

IV exendin(9-39) plus intraduodenal (ID) saline

Active Comparator group

Description:

intravenous infusion of exendin(9-39) plus intraduodenal administration of saline

Treatment:

Drug: Exendin 9-39

IV saline, intraduodenal nutrient

Placebo Comparator group

Description:

intravenous infusion of saline plus intraduodenal administration of nutrient

Treatment:

Dietary Supplement: Saline

Dietary Supplement: Saline

Exendin(9-39) plus ID nutrient

Active Comparator group

Description:

Exendin(9-39) as intravenous infusion plus intraduodenal nutrient administration

Treatment:

Drug: Exendin(9-39) plus ID nutrient