Pharmacogenomics of GLP1 Receptor Agonists
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- Exenatide Effect on First Phase Insulin Secretion
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
盲法说明
Participants were not informed whether the nurse was administering saline or exenatide injections.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Member of the Old Order Amish community in Lancaster County, Pennsylvania
- •BMI: 18-40 kg/sq.m.
排除标准
- •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.
研究组 & 干预措施
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
干预措施: Exenatide Injection (before the first FSIGT) (Drug)
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
干预措施: Exenatide injection before the second FSIGT) (Drug)
结局指标
主要结局
Exenatide Effect on First Phase Insulin Secretion
时间窗: 0-10 minutes
The ratio of the area-under-the-curve (AUC) for 1st phase insulin secretion in the exenatide-stimulated FSIGT divided by the AUC for 1st phase insulin secretion in the saline FSIGT.
Exenatide Effect on Glucose Disappearance Rate
时间窗: 25-50 minutes
The ratio of the glucose disappearance rate (exenatide) divided by the glucose disappearance rate (placebo). Glucose disappearance rates were calculated as the slope of the plot of the logarithm of the glucose concentration as a function of time.
次要结局
- Glucose Disappearance Rate (Exenatide)(25-50 minutes)
- Glucose Disappearance Rate (Placebo)(25-50 minutes)
- First Phase Insulin Secretion (Exenatide)(0-10 minutes)
- First Phase Insulin Secretion (Placebo)(0-10 minutes)
- Drug Effect on First-Phase Insulin Secretion (Genotype-specific)(0 - 10 min during the FSIGT)
- Exenatide's Effect on the Rate of Glucose-disappearance (Genotype Specific)(25-50 min during the FSIGT)
研究者
Simeon I. Taylor
Professor of Medicine
University of Maryland, Baltimore