GLP1R Polymorphisms and Response to GLP1

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Adrian Vella, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00588380
First received: December 22, 2007
Last updated: December 14, 2011
Last verified: December 2011

December 22, 2007
December 14, 2011
November 2007
September 2010   (final data collection date for primary outcome measure)
Insulin Secretion at 150-180 Minutes. [ Time Frame: 150 - 180 minutes after GLP-1 infusion ] [ Designated as safety issue: No ]
The 180 minute value represents the mean of the values obtained at 150, 160, 170, and 180 minutes.
The focus of the analysis during the hyperglycemic clamp is the mean C-peptide concentrations at 150-180 minutes. [ Time Frame: during the study ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00588380 on ClinicalTrials.gov Archive Site
Insulin Secretion at 210-240 Minutes [ Time Frame: 210 - 240 minutes after GLP-1 infusion ] [ Designated as safety issue: No ]
The 240 minute value represents the mean of values obtained at 210, 220, 230, and 240 minutes.
The secondary focus of the analysis during the hyperglycemic clamp is the mean C-peptide concentrations at 210-240 minutes. [ Time Frame: during the study ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
GLP1R Polymorphisms and Response to GLP1
A Pilot Study Examining How Common Genetic Variation in GLP1R Alters Response to GLP1 Infusion

Glucagon-like Peptide-1 (GLP-1) is an important incretin hormone which acts as a powerful insulin secretagogue. Defects in GLP-1 synthesis and secretion are thought to be part of the pathogenesis of type 2 diabetes. Furthermore GLP-1 based therapy is an important part of the therapeutic armamentarium for the treatment of type 2 diabetes. The GLP-1 receptor (GLP1R) is the principal site of action of GLP-1 and GLP-1 receptor agonists like exenatide and liraglutide. The gene coding for this receptor, GLP1R, is highly polymorphic and contains numerous non-synonymous Single Nucleotide Polymorphisms (nsSNPs) which could potentially alter response to endogenous or exogenous GLP-1 or GLP-1R agonists. Indeed there is some in vitro data to support this concept. We propose to utilize a hyperglycemic clamp to test the insulin secretory response to infused GLP-1 in healthy volunteers to determine the effect of genetic variation in GLP1R on response to GLP-1.

Not Provided
Interventional
Not Provided
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Diabetes
Drug: GLP-1
GLP-1 infused at 0.75 pmol/kg/min from 121-180 minutes, GLP-1 infused at 1.55 pmol/kg/min from 181-240 minutes,
Experimental: GLP-1
All participants recieved GLP-1 intravenously at 0.75 pmol/kg/min for the first hour and then at 1.5 pmol/kg/min for the next hour
Intervention: Drug: GLP-1
Sathananthan A, Man CD, Micheletto F, Zinsmeister AR, Camilleri M, Giesler PD, Laugen JM, Toffolo G, Rizza RA, Cobelli C, Vella A. Common genetic variation in GLP1R and insulin secretion in response to exogenous GLP-1 in nondiabetic subjects: a pilot study. Diabetes Care. 2010 Sep;33(9):2074-6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
88
September 2010
September 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Aged 18-40
  • fasting glucose concentration of less than 95 mg/dl.

Exclusion Criteria:

  • Individuals with a BMI < 19 or > 40 kg/m^2
  • active systemic illness
  • medication that can alter gastric emptying, insulin secretion & action
  • history of abdominal surgery (other than appendectomy or tubal ligation).
Both
18 Years to 40 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00588380
07-004153
No
Adrian Vella, Mayo Clinic
Mayo Clinic
Merck Sharp & Dohme Corp.
Principal Investigator: Adrian Vella, MD Mayo Clinic
Mayo Clinic
December 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP