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

NCT ID: NCT01900340

Last Updated: 2013-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2012-12-31

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.

Conditions

Appetite and General Nutritional Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

iv saline, intraduodenal saline

intravenous infusion of saline plus intraduodenal administration of saline

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DIETARY_SUPPLEMENT

Intravenous saline infusion and intraduodenal administration of saline via feeding tube

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

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

Group Type: ACTIVE_COMPARATOR

Exendin 9-39

Intervention Type: DRUG

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

IV saline, intraduodenal nutrient

intravenous infusion of saline plus intraduodenal administration of nutrient

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DIETARY_SUPPLEMENT

IV saline infusion and intraduodenal administration of nutrients

Exendin(9-39) plus ID nutrient

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

Group Type: ACTIVE_COMPARATOR

Exendin(9-39) plus ID nutrient

Intervention Type: DRUG

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

Interventions

Saline

Intravenous saline infusion and intraduodenal administration of saline via feeding tube

Intervention Type: DIETARY_SUPPLEMENT

Exendin 9-39

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

Intervention Type: DRUG

Saline

IV saline infusion and intraduodenal administration of nutrients

Intervention Type: DIETARY_SUPPLEMENT

Exendin(9-39) plus ID nutrient

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christoph Beglinger, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Basel, Phase 1 Research Unit, Basel Switzerland

Locations

University Hospital Basel, Phase 1 Research Unit

Basel, , Switzerland

Countries

Switzerland

References

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.

Reference Type: DERIVED

PMID: 24965303 (View on PubMed)

Other Identifiers

EKBB 25/11

Identifier Type: -

Identifier Source: org_study_id