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
  Purpose

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 Intervention
Diabetes
Drug: GLP-1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Pilot Study Examining How Common Genetic Variation in GLP1R Alters Response to GLP1 Infusion

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 88
Study Start Date: November 2007
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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,

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00588380

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

Additional Information:
Publications:
Responsible Party: Adrian Vella, Professor of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00588380     History of Changes
Other Study ID Numbers: 07-004153
Study First Received: December 22, 2007
Results First Received: April 4, 2011
Last Updated: December 14, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
GLP-1
Insulin Secretion

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

ClinicalTrials.gov processed this record on April 17, 2014