Clinical trial NCT05762744: Pharmacogenomics of GLP1 Receptor Agonists
Official title: Pharmacogenomics of GLP1 Receptor Agonists
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Type 2 Diabetes
Keywords: GLP1
insulin
glucose
exenatide
GLP1 receptor agonist
insulin secretion
glucagon receptor
GIP receptor
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
First posted: 2023-03-10
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Research participants all received the same two interventions (saline or exenatide) but the order of the interventions was randomized.
Primary purpose: BASIC_SCIENCE

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).

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).

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

Primary outcomes:
measure: First phase insulin secretion (placebo)
timeFrame: 0-10 minutes
measure: First phase insulin secretion (exenatide)
timeFrame: 0-10 minutes
measure: Exenatide effect on first phase insulin secretion
timeFrame: 0-10 minutes
measure: glucose disappearance rate (placebo)
timeFrame: 25-50 minutes
measure: glucose disappearance rate (exenatide)
timeFrame: 25-50 minutes
measure: Exenatide effect on glucose disappearance rate
timeFrame: 25-50 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Lancaster
country: United States
facility: Amish Research Clinic
state: Pennsylvania
Study officials:
affiliation: University of Maryland, Baltimore
name: Simeon I Taylor, MD
role: PRINCIPAL_INVESTIGATOR
References: