Appetite and General Nutritional Disorders
Conditions
Keywords
GLP-1, satiation peptides, food intake
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.
Interventions
DIETARY_SUPPLEMENTSaline
Intravenous saline infusion and intraduodenal administration of saline via feeding tube
DRUGExendin 9-39
IV exendin(9-39) infusion and intraduodenal administration of saline via feeding tube
DRUGExendin(9-39) plus ID nutrient
Exendin(9-39) as intravenous infusion plus intraduodenal nutrient administration
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 glucose | 4 hours blood sampling |
| Effect of exendin(9-39)on plasma concentration of ghrelin. | 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 insulin. | 4 hours blood sampling |
| Effect of exendin(9-39)on plasma concentration of glucagon. | 4 hours blood sampling |
Countries
Switzerland
Outcome results
None listed