Pharmacogenomics of GLP1 Receptor Agonists

NCT ID: NCT05762744

Last Updated: 2025-07-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-01
• Study Completion Date: 2022-10-31

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. However, because the study fell far short of its recruitment targets, it was under-powered to evaluate genetic association. Thus, the data analysis focused on testing the hypothesis that the order of testing (whether the placebo FSIGT was conducted before the exenatide-stimulated FSIGT or whether the FSIGTs were conducted in the reverse order) does not alter the magnitude impact of exenatide on responses to a frequently sampled iv glucose tolerance test.

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. However, because the study fell far short of its recruitment targets, it was under-powered to evaluate genetic association. Thus, the data analysis focused on testing the hypothesis that the order of testing (whether the placebo FSIGT was conducted before the exenatide-stimulated FSIGT or whether the FSIGTs were conducted in the reverse order) does not alter the magnitude impact of exenatide on responses to a frequently sampled iv glucose tolerance test.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Exenatide followed by saline

Participants were randomized to receive exenatide 15 min before the first frequently sampled iv glucose tolerance test and saline 15 min before the second frequently sampled iv glucose tolerance test

Group Type: OTHER

Exenatide Injection (before the first FSIGT)

Intervention Type: DRUG

Nurses administered exenatide (5 mcg) subcutaneously 15 minutes prior to conducting the first frequently sampled intravenous glucose tolerance test.

In this crossover study, participants will also be "crossed over" to receive saline rather than exenatide: Nurses administered saline (0.2 mL) subcutaneously 15 minutes prior to conducting a frequently sampled intravenous glucose tolerance test.

Saline followed by exenatide

Participants were randomized to receive saline15 min before the first frequently sampled iv glucose tolerance test and exenatide15 min before the second frequently sampled iv glucose tolerance test

Group Type: OTHER

Exenatide injection before the second FSIGT)

Intervention Type: DRUG

Nurses administered exenatide (5 mcg) subcutaneously 15 minutes prior to conducting the second frequently sampled intravenous glucose tolerance test.

Interventions

Exenatide Injection (before the first FSIGT)

Nurses administered exenatide (5 mcg) subcutaneously 15 minutes prior to conducting the first frequently sampled intravenous glucose tolerance test.

In this crossover study, participants will also be "crossed over" to receive saline rather than exenatide: Nurses administered saline (0.2 mL) subcutaneously 15 minutes prior to conducting a frequently sampled intravenous glucose tolerance test.

Intervention Type: DRUG

Exenatide injection before the second FSIGT)

Nurses administered exenatide (5 mcg) subcutaneously 15 minutes prior to conducting the second frequently sampled intravenous glucose tolerance test.

Intervention Type: DRUG

Other Intervention Names

BYETTA; Exenatide; BYETTA; Exenatide

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Simeon I. Taylor

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Simeon I Taylor, MD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Locations

Amish Research Clinic

Lancaster, Pennsylvania, United States

Countries

United States

References

Taylor SI, Montasser ME, Yuen AH, Fan H, Yazdi ZS, Whitlatch HB, Mitchell BD, Shuldiner AR, Muniyappa R, Streeten EA, Beitelshees AL. Acute pharmacodynamic responses to exenatide: Drug-induced increases in insulin secretion and glucose effectiveness. Diabetes Obes Metab. 2023 Sep;25(9):2586-2594. doi: 10.1111/dom.15143. Epub 2023 Jun 1.

Reference Type: BACKGROUND

PMID: 37264484 (View on PubMed)

Beitelshees AL, Streeten EA, Shahidzadeh Yazdi Z, Whitlatch HB, Mitchell BD, Shuldiner AR, Montasser ME, Taylor SI. Acute pharmacodynamic responses to sitagliptin: Drug-induced increase in early insulin secretion in oral glucose tolerance test. Clin Transl Sci. 2024 May;17(5):e13809. doi: 10.1111/cts.13809.

Reference Type: DERIVED

PMID: 38700326 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

HP-00067574

Identifier Type: -

Identifier Source: org_study_id