GLP1R Polymorphisms and Response to GLP1

Diabetes Clinical Trial

Official title:

A Pilot Study Examining How Common Genetic Variation in GLP1R Alters Response to GLP1 Infusion

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00588380
• Other study ID #: 07-004153
• Status: Completed
• Phase: N/A
• First received: December 22, 2007
• Last updated: December 14, 2011
• Start date: November 2007
• Est. completion date: September 2010

Study information

• Verified date: December 2011
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

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).

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes

Intervention

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,

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (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 stud — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin Secretion at 150-180 Minutes.	The 180 minute value represents the mean of the values obtained at 150, 160, 170, and 180 minutes.	150 - 180 minutes after GLP-1 infusion	No
Secondary	Insulin Secretion at 210-240 Minutes	The 240 minute value represents the mean of values obtained at 210, 220, 230, and 240 minutes.	210 - 240 minutes after GLP-1 infusion	No

External Links

•   Mayo Clinic Clinical Trials