GLP1R Polymorphisms and Response to GLP1

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00588380
Recruitment Status : Completed
First Posted : January 8, 2008
Results First Posted : December 6, 2011
Last Update Posted : December 19, 2011
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Adrian Vella, Mayo Clinic

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diabetes Drug: GLP-1 Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Pilot Study Examining How Common Genetic Variation in GLP1R Alters Response to GLP1 Infusion
Study Start Date : November 2007
Actual Primary Completion Date : September 2010
Actual Study Completion Date : September 2010

Arm Intervention/treatment
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
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,

Primary Outcome Measures :
  1. Insulin Secretion at 150-180 Minutes. [ Time Frame: 150 - 180 minutes after GLP-1 infusion ]
    The 180 minute value represents the mean of the values obtained at 150, 160, 170, and 180 minutes.

Secondary Outcome Measures :
  1. Insulin Secretion at 210-240 Minutes [ Time Frame: 210 - 240 minutes after GLP-1 infusion ]
    The 240 minute value represents the mean of values obtained at 210, 220, 230, and 240 minutes.

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00588380

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Merck Sharp & Dohme Corp.
Principal Investigator: Adrian Vella, MD Mayo Clinic

Additional Information:
Publications of Results:
Responsible Party: Adrian Vella, Professor of Medicine, Mayo Clinic Identifier: NCT00588380     History of Changes
Other Study ID Numbers: 07-004153
First Posted: January 8, 2008    Key Record Dates
Results First Posted: December 6, 2011
Last Update Posted: December 19, 2011
Last Verified: December 2011

Keywords provided by Adrian Vella, Mayo Clinic:
Insulin Secretion

Additional relevant MeSH terms:
Glucagon-Like Peptide 1
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Gastrointestinal Agents