Pharmacogenomics of GLP1 Receptor Agonists

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Terminated
• CT.gov ID: NCT05762744
• Collaborator: (none)
• Enrollment: 78
• Location: 1
• Arms: 3
• Actual Duration (Months): 77
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Exenatide Injection; Drug: Saline injection	Phase 1

Detailed 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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 78 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Research participants all received the same two interventions (saline or exenatide) but the order of the interventions was randomized.Research participants all received the same two interventions (saline or exenatide) but the order of the interventions was randomized.
• Masking: Single (Participant)
• Masking Description: Participants were not informed whether the nurse was administering saline or exenatide injections.
• Primary Purpose: Basic Science
• Official Title: Pharmacogenomics of GLP1 Receptor Agonists
• Actual Study Start Date: Jun 1, 2016
• Actual Primary Completion Date: Nov 30, 2018
• Actual Study Completion Date: Oct 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Other: Homozygous for major alleles of GCGR and GIPR Based on data in a genotype database, these individuals were homozygous for the "wild type" major alleles of both GCGR and GIPR.	Drug: Exenatide Injection; Nurses administered exenatide (5 mcg) subcutaneously 15 minutes prior to conducting a frequently sampled intravenous glucose tolerance test.; Other Names: BYETTA ; Drug: Saline injection; Nurses administered saline (0.2 mL) subcutaneously 15 minutes prior to conducting a frequently sampled intravenous glucose tolerance test.
Other: Homozygous for missense variant in GIPR Based on data in a genotype database, these individuals were homozygous for rs1800437 a missense variant (p.E354Q) in the GIP receptor gene (GIPR).	Drug: Exenatide Injection; Nurses administered exenatide (5 mcg) subcutaneously 15 minutes prior to conducting a frequently sampled intravenous glucose tolerance test.; Other Names: BYETTA ; Drug: Saline injection; Nurses administered saline (0.2 mL) subcutaneously 15 minutes prior to conducting a frequently sampled intravenous glucose tolerance test.
Other: Homozygous for missense variant in GCGR Based on data in a genotype database, these individuals were homozygous for rs1801483a missense variant (p.G40S) in the glucagon receptor gene (GCGR).	Drug: Exenatide Injection; Nurses administered exenatide (5 mcg) subcutaneously 15 minutes prior to conducting a frequently sampled intravenous glucose tolerance test.; Other Names: BYETTA ; Drug: Saline injection; Nurses administered saline (0.2 mL) subcutaneously 15 minutes prior to conducting a frequently sampled intravenous glucose tolerance test.

Outcome Measures

Primary Outcome Measures

1. First phase insulin secretion (placebo) [0-10 minutes]

   The area under the curve for plasma insulin levels during a frequently sampled intravenous glucose tolerance test after participants received saline

2. First phase insulin secretion (exenatide) [0-10 minutes]

   The area under the curve for plasma insulin levels during a frequently sampled intravenous glucose tolerance test after participants received exenatide

3. Exenatide effect on first phase insulin secretion [0-10 minutes]

   The difference between the logarithm of first phase insulin secretion (exenatide) minus the logarithm of the first phase insulin secretion (placebo)

4. glucose disappearance rate (placebo) [25-50 minutes]

   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

5. glucose disappearance rate (exenatide) [25-50 minutes]

   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

6. Exenatide effect on glucose disappearance rate [25-50 minutes]

   The difference between glucose disappearance rate (exenatide) minus glucose disappearance rate (placebo)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Amish Research Clinic	Lancaster	Pennsylvania	United States	17602

Sponsors and Collaborators

• University of Maryland, Baltimore

Investigators

• Principal Investigator: Simeon I Taylor, MD, University of Maryland School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Simeon I. Taylor, Professor of Medicine, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT05762744
• Other Study ID Numbers: HP-00067574
• First Posted: Mar 10, 2023
• Last Update Posted: Mar 10, 2023
• Last Verified: Mar 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Simeon I. Taylor, Professor of Medicine, University of Maryland, Baltimore: GLP1; insulin; glucose; exenatide; GLP1 receptor agonist; insulin secretion; glucagon receptor; GIP receptor
• Additional relevant MeSH terms: Exenatide

Study Results

No Results Posted as of Mar 10, 2023