Clinical trial NCT01900340: Intestinal Glucagon-like Peptide-1 (GLP-1) and the Physiological Role in Eating in Humans
Official title: Intestinal Glucagon-like Peptide-1 (GLP-1) and the Physiological Role in Eating in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Appetite and General Nutritional Disorders
Keywords: GLP-1
satiation peptides
food intake
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2013-07-16
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility 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

Primary outcomes:
measure: Effect of exendin(9-39)on total calorie intake
timeFrame: 60 min test meal
measure: Effect of exendin(9-39) on total fluid intake
timeFrame: 60 min test meal
measure: Effect of exendin(9-39)on meal duration during an ad libitum test meal.
timeFrame: 60 min test meal
Secondary outcomes:
measure: Effect of exendin(9-39)on plasma concentration of glucose
timeFrame: 4 hours blood sampling
measure: Effect of exendin(9-39)on plasma concentration of insulin.
timeFrame: 4 hours blood sampling
measure: Effect of exendin(9-39)on plasma concentration of glucagon.
timeFrame: 4 hours blood sampling
measure: Effect of exendin(9-39)on plasma concentration of GLP-1.
timeFrame: 4 hours blood sampling
measure: Effect of exendin(9-39)on plasma concentration of peptide tyrosine tyrosine (PYY).
timeFrame: 4 hours blood sampling
measure: Effect of exendin(9-39)on plasma concentration of CCK.
timeFrame: 4 hours blood sampling
measure: Effect of exendin(9-39)on plasma concentration of ghrelin.
timeFrame: 4 hours blood sampling
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Phase 1 Research Unit
Study officials:
affiliation: University Hospital Basel, Phase 1 Research Unit, Basel Switzerland
name: Christoph Beglinger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Steinert RE, Schirra J, Meyer-Gerspach AC, Kienle P, Fischer H, Schulte F, Goeke B, Beglinger C. Effect of glucagon-like peptide-1 receptor antagonism on appetite and food intake in healthy men. Am J Clin Nutr. 2014 Aug;100(2):514-23. doi: 10.3945/ajcn.114.083246. Epub 2014 Jun 25.