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

Appetite and General Nutritional Disorders Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01900340
• Other study ID #: EKBB 25/11
• Status: Completed
• Phase: Phase 1
• First received: April 3, 2012
• Last updated: July 11, 2013
• Start date: November 2011
• Est. completion date: December 2012

Study information

• Verified date: July 2013
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Ethikkommission
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Appetite and General Nutritional Disorders
• Nutrition Disorders

Intervention

Dietary Supplement:
• Saline
Intravenous saline infusion and intraduodenal administration of saline via feeding tube

Drug:
• Exendin 9-39
IV exendin(9-39) infusion and intraduodenal administration of saline via feeding tube

Dietary Supplement:
• Saline
IV saline infusion and intraduodenal administration of nutrients

Drug:
• Exendin(9-39) plus ID nutrient
Exendin(9-39) as intravenous infusion plus intraduodenal nutrient administration

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Phase 1 Research Unit	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of exendin(9-39)on total calorie intake		60 min test meal	No
Primary	Effect of exendin(9-39) on total fluid intake		60 min test meal	No
Primary	Effect of exendin(9-39)on meal duration during an ad libitum test meal.		60 min test meal	No
Secondary	Effect of exendin(9-39)on plasma concentration of glucose		4 hours blood sampling	No
Secondary	Effect of exendin(9-39)on plasma concentration of insulin.		4 hours blood sampling	No
Secondary	Effect of exendin(9-39)on plasma concentration of glucagon.		4 hours blood sampling	No
Secondary	Effect of exendin(9-39)on plasma concentration of GLP-1.		4 hours blood sampling	No
Secondary	Effect of exendin(9-39)on plasma concentration of peptide tyrosine tyrosine (PYY).		4 hours blood sampling	No
Secondary	Effect of exendin(9-39)on plasma concentration of CCK.		4 hours blood sampling	No
Secondary	Effect of exendin(9-39)on plasma concentration of ghrelin.		4 hours blood sampling	No