Pharmacogenomics of GLP1 Receptor Agonists

Type 2 Diabetes Clinical Trial

Official title:

Pharmacogenomics of GLP1 Receptor Agonists

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05762744
• Other study ID #: HP-00067574
• Status: Terminated
• Phase: Phase 1
• Start date: June 1, 2016
• Est. completion date: October 31, 2022

Study information

• Verified date: March 2023
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Healthy volunteers were recruited from the Old Order Amish population in Lancaster County, Pennsylvania. After providing informed consent, research participants were screened for eligibility. The clinical trial was designed as a randomized crossover study in which participants underwent two frequently sampled intravenous glucose tolerance tests - one after receiving a subcutaneous injection of saline and one after receiving a subcutaneous injection of rapid-acting exenatide (BYETTA). The study sought to determine whether genetic variants are associated with the magnitude of the effect of exenatide. If an association were identified, this would help physicians to predict whether an individual patient is likely to have a large response to the class of diabetes drugs to which exenatide belongs (GLP1 receptor agonists).

Description:

Healthy volunteers were recruited from the Old Order Amish population in Lancaster County, Pennsylvania. After providing informed consent, research participants were screened for eligibility. The clinical trial was designed as a randomized crossover study in which participants underwent two frequently sampled intravenous glucose tolerance tests (FSIGT) - one after receiving a subcutaneous injection of saline and one after receiving a subcutaneous injection of rapid-acting exenatide (BYETTA). Based on data obtained from the FSIGT, participants' response to exenatide was assessed -- specifically, the effect of exenatide to enhance insulin secretion and accelerate metabolism of glucose. The study sought to determine whether genetic variants are associated with the magnitude of the effect of exenatide. If an association were identified, this would help physicians to predict whether an individual patient is likely to have a large response to the class of diabetes drugs to which exenatide belongs (GLP1 receptor agonists).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 78
• Est. completion date: October 31, 2022
• Est. primary completion date: November 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Member of the Old Order Amish community in Lancaster County, Pennsylvania

• BMI: 18-40 kg/sq.m.

Exclusion Criteria:

• Known allergy to exenatide

• History of diabetes, random glucose >200 mg/dL, or HbA1c > 6.5%

• Significant debilitating chronic cardiac, hepatic, pulmonary, or renal disease or other diseases that the investigator judges will make interpretation of the results difficult or increase the risk of participation

• Seizure disorder

• Pregnant by self-report or known pregnancy within 3 months of the start of study

• Currently breast feeding or breast feeding within 3 months of the start of the study

• Estimated glomerular filtration rate <60 mL/min/1.73m2

• Hematocrit <35%

• Liver function tests greater than 2 times the upper limit of normal

• Abnormal TSH

• History of pancreatitis or pancreatic cancer. Personal or family history of medullary carcinoma of the thyroid.

Related Conditions & MeSH terms

• Type 2 Diabetes

Intervention

Drug:
• Exenatide Injection
Nurses administered exenatide (5 mcg) subcutaneously 15 minutes prior to conducting a frequently sampled intravenous glucose tolerance test.
• Saline injection
Nurses administered saline (0.2 mL) subcutaneously 15 minutes prior to conducting a frequently sampled intravenous glucose tolerance test.

Locations

Country	Name	City	State
United States	Amish Research Clinic	Lancaster	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Maryland, Baltimore

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	First phase insulin secretion (placebo)	The area under the curve for plasma insulin levels during a frequently sampled intravenous glucose tolerance test after participants received saline	0-10 minutes
Primary	First phase insulin secretion (exenatide)	The area under the curve for plasma insulin levels during a frequently sampled intravenous glucose tolerance test after participants received exenatide	0-10 minutes
Primary	Exenatide effect on first phase insulin secretion	The difference between the logarithm of first phase insulin secretion (exenatide) minus the logarithm of the first phase insulin secretion (placebo)	0-10 minutes
Primary	glucose disappearance rate (placebo)	The slope of the line plotting the logarithm of glucose concentrations as a function of time during the placebo frequently sampled intravenous glucose tolerance test	25-50 minutes
Primary	glucose disappearance rate (exenatide)	The slope of the line plotting the logarithm of glucose concentrations as a function of time during the exenatide frequently sampled intravenous glucose tolerance test	25-50 minutes
Primary	Exenatide effect on glucose disappearance rate	The difference between glucose disappearance rate (exenatide) minus glucose disappearance rate (placebo)	25-50 minutes