Exendin(9-39)Amide as a Glucagon-like Peptide-1 (GLP-1) Receptor Antagonist in Humans
|First Received Date ICMJE||October 26, 2006|
|Last Updated Date||October 2, 2011|
|Start Date ICMJE||November 2006|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||To assess the effect of increasing doses of exendin(9-39) on first and second phase insulin secretion stimulated by intravenous GLP-1 during hyperglycemia [ Time Frame: within the actual study period ]|
|Original Primary Outcome Measures ICMJE
||To assess the effect of increasing doses of exendin(9-39) on plasma insulin levels stimulated by intravenous GLP-1 during hyperglycemia.|
|Change History||Complete list of historical versions of study NCT00393445 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||To assess the effect of increasing doses of exendin(9-39) on plasma glucagon levels decreased by intravenous GLP-1 during hyperglycemia [ Time Frame: within the actual study period ]|
|Original Secondary Outcome Measures ICMJE
||To assess the effect of increasing doses of exendin(9-39) on plasma glucagon levels decreased by intravenous GLP-1 during hyperglycemia.|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Exendin(9-39)Amide as a Glucagon-like Peptide-1 (GLP-1) Receptor Antagonist in Humans|
|Official Title ICMJE||Effect of GLP-1 on Glucose Metabolism in Healthy Subjects and Patients With T2DM. Part 1: A Pilot Study to Assess the Efficacy of Exendin(9-39)Amide as a GLP-1 Receptor Antagonist in Healthy Subjects|
The purpose of this study is to determine the dose of the GLP-1 receptor antagonist exendin(9-39) which blocks the insulinotropic action of synthetic GLP-1 by at least 95%.
Following a meal, gut-produced incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the circulation. GLP-1 and GIP, the two dominant incretin hormones, are part of a natural endogenous system involved in maintaining glucose homeostasis. In the presence of normal or elevated, but not low, glucose concentration, both GLP-1 and GIP increase insulin secretion from pancreatic islet beta-cells (β-cells). GLP-1 also lowers glucagon secretion from pancreatic alpha-cells and delays nutrient delivery from the stomach by inhibiting gastric emptying. This rise in insulin concentration enhances glucose clearance in peripheral tissues such as muscle, and the lower glucagon concentration combined with the rise in insulin reduces hepatic glucose production. By enhancing glucose clearance and lowering hepatic glucose production, the post-meal glucose excursion is reduced.
However, the role that each incretin has in glucoregulation is not fully understood. Use of a GLP-1 antagonist, exendin (9-39)NH2, will allow for the assessment of non-GLP-1 incretin's role in glucoregulation. Therefore, it is of great interest to examine the role that specific incretins have in glucoregulation in patients with T2DM.
Exendin(9-39) has been shown a specific and reversible antagonist at the human GLP-1 receptor in vivo. In initial validation studies intravenous exendin(9-39) dose-dependently reduced the insulinotropic action of intravenous GLP-1. The maximal dose of 300 pmol/kg/min used in these studies was sufficient to reduce GLP-1 stimulated insulin plasma levels by about 83%. However, to quantify the contribution of incretin hormones to the incretin effect as stated above a nearly complete inhibition of the GLP-1 action is necessary.
Therefore the purpose of this pilot study is to characterize the dose-response characteristics of exendin(9-39) more completely and to find a dosage which inhibits the insulinotropic action of GLP-1 by at least 95%.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Diagnostic
|Study Arm (s)||Experimental: Intravenous infusion
intravenous infusion of test substances
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||May 2007|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 65 Years|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||Germany|
|NCT Number ICMJE||NCT00393445|
|Other Study ID Numbers ICMJE||DOF-Ex, DFG Schi 527/1-2|
|Has Data Monitoring Committee||No|
|Responsible Party||Joerg Schirra, Ludwig-Maximilians - University of Munich|
|Study Sponsor ICMJE||Ludwig-Maximilians - University of Munich|
|Information Provided By||Ludwig-Maximilians - University of Munich|
|Verification Date||October 2011|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP