GIP/GLP-1 Co-Activity in Subjects With Obesity: Lowering of Food Intake

Obesity Clinical Trial

— GASOLIN  

Official title:

GIP/GLP-1 Co-Activity in Subjects With Obesity: Lowering of Food Intake

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02598791
• Other study ID #: H-15008790 (GASOLIN)
• Status: Completed
• Phase: N/A
• Start date: October 1, 2015
• Est. completion date: June 20, 2016

Study information

• Verified date: December 2018
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

We aim to delineate the effects of separate and combined infusion of GIP and GLP-1 on food intake, appetite, bone health and fat metabolism in overweight/obese subjects.

Description:

The gut-derived incretin glucagon-like peptide-1 (GLP-1) is a potent regulator of gastric emptying, appetite and food intake in humans whereas its sister incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), does not seem to have independent effects on these variables in humans. Interestingly, recent data from rodents have shown that concomitant activation of the GIP and the GLP-1 receptor may potentiate the satiety-promoting and body weight-reducing effects of GLP-1. Also, evidence suggests that GIP may be an important mediator of bone remodelling and lipid deposition. The effect of simultaneous activation of the GIP and GLP-1 receptors on appetite, food intake, fat metabolism and bone health has not been thoroughly examined in humans. The aim of this study is to delineate the effects of GIP/GLP-1 receptor co-activation on food intake, mechanisms regulating food intake, fat and bone metabolism in obese subjects.

Material and methods:

The investigators plan to include 18 obese/overweight men without diabetes. The primary endpoint of the study is food intake during continuous intravenous infusions of saline (placebo), GIP, GLP-1 and GIP+GLP-1, respectively. Secondary endpoints includes resting energy expenditure (measured by indirect calorimetry), appetite, satiety and hunger assessments (measured by visual analogue scales), plasma insulin, C-peptide and glucagon secretion, plasma triglycerides, cholesterols, and free fatty acid responses and changes in plasma bone turnover markers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: June 20, 2016
• Est. primary completion date: June 20, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 25 Years to 70 Years

Eligibility

Inclusion Criteria:

• Caucasian men

• Age between 25 and 70 years

• Body mass index (BMI) between 25 and 40 kg/m2

Exclusion Criteria:

• Diabetes or prediabetes (defined as glycated haemoglobin (HbA1c) = 43 mmol/mol)

• Anaemia (defined as haemoglobin < 8.3 mmol/l)

• Any gastrointestinal disease that may interfere with the endpoint variables

• Anorexia, bulimia or binge eating disorder

• Allergy or intolerance to ingredients included in the standardised meals

• Tobacco smoking

• Any regular drug treatment that cannot be discontinued for minimum 18 hours

• Any physical or psychological condition that the investigator feels would interfere with trial participation

Related Conditions & MeSH terms

• Adiposity
• Obesity
• Type 2 Diabetes

Intervention

Other:
• IIGI+GIP
Glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemia
• IIGI+GLP-1
glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemia
• IIGI+NaCl (placebo)
i.v. NaCl during isoglycemia
• OGTT
50 g oral glucose tolerance test
• IIGI+GIP+GLP-1
i.v infusion of GIP and GLP-1 (4 + 1 pmol/kg/min) during isoglycemia

Locations

Country	Name	City	State
Denmark	Center for Diabetesresearch, Gentofte hospital	Hellerup

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen

Country where clinical trial is conducted

Denmark, 

References & Publications (4)

Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013 Jun 4;17(6):819-37. doi: 10.1016/j.cmet.2013.04.008. Epub 2013 May 16. Review. — View Citation

Finan B, Ma T, Ottaway N, Müller TD, Habegger KM, Heppner KM, Kirchner H, Holland J, Hembree J, Raver C, Lockie SH, Smiley DL, Gelfanov V, Yang B, Hofmann S, Bruemmer D, Drucker DJ, Pfluger PT, Perez-Tilve D, Gidda J, Vignati L, Zhang L, Hauptman JB, Lau M, Brecheisen M, Uhles S, Riboulet W, Hainaut E, Sebokova E, Conde-Knape K, Konkar A, DiMarchi RD, Tschöp MH. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans. Sci Transl Med. 2013 Oct 30;5(209):209ra151. doi: 10.1126/scitranslmed.3007218. — View Citation

Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest. 1998 Feb 1;101(3):515-20. — View Citation

Nissen A, Christensen M, Knop FK, Vilsbøll T, Holst JJ, Hartmann B. Glucose-dependent insulinotropic polypeptide inhibits bone resorption in humans. J Clin Endocrinol Metab. 2014 Nov;99(11):E2325-9. doi: 10.1210/jc.2014-2547. Epub 2014 Aug 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	food intake	How much does the participant eat of from the ad libitum meal, measured in gram	250-280 min
Secondary	hunger	feeling of hunger measured on a visual analogue scale	measured at time 0, 30, 60, 90, 120, 180, 210, 240 min
Secondary	satiety	feeling of satiety measured on a visual analogue scale	measured at time 0, 30, 60, 90, 120, 180, 210, 240 min
Secondary	Fullness	feeling of fullness measured on a visual analogue scale	measured at time 0, 30, 60, 90, 120, 180, 210, 240 min
Secondary	Prospective food consumption	Prospective food consumption measured on a visual analogue scale	measured at time 0, 30, 60, 90, 120, 180, 210, 240 min
Secondary	resting energy expenditure (REE)	changes in REE measured by a ventilated hood 15 minutes at baseline and 15 minutes at time point 210 min.	-15 to 0 min. and 210 to 225 min.
Secondary	Insulin	changes in insulin measured in serum	-30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min
Secondary	C-peptide level	changes in C-peptide level measured in serum	-30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min
Secondary	glucagon levels	changes in glucagon levels measured in plasma	-30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min
Secondary	Cholesterol and FFA	changes in cholesterol (TAG, Total cholesterol and free fatty acid measured in plasma)	-30, 0, 30, 60, 90, 120, 180, 240 min
Secondary	C-terminal cross-linked telopeptide of bone collagen (CTX)	changes in level of CTX measured in plasma	-30, 0, 30, 60, 90, 120, 180, 240 min
Secondary	procollagen type 1 N-terminal propeptide (P1NP)	changes in level of P1NP measured in plasma	-30, 0, 30, 60, 90, 120, 180, 240 min