Role of GLP-1 in Congenital Hyperinsulinism:Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Area Under the Curve (AUC) Plasma Glucose
研究概览
简要总结
The purpose of this study is to examine the effects of exendin-(9-39) on fasting blood glucose and protein induced hypoglycemia on subjects with Congenital Hyperinsulinism. Funding Source - FDA Office of Orphan Products Development (OODP).
详细描述
This is a placebo controlled study with randomized crossover design to evaluate the effect of the glucagon-like peptide-1 (GLP-1) receptor antagonist, exendin-(9-39), on fasting blood glucose levels, protein-induced hypoglycemia, and fasting tolerance of subjects with congenital hyperinsulinism due to mutations in the ATP- sensitive potassium channel (KATP) channel.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of hyperinsulinism
- •Mutation analysis results demonstrating KATP channel defect
- •Age 6 months to 18 years with
- •Persistent hypoglycemia
排除标准
- •Current therapy with medications that may affect glucose metabolism such as octreotide, diazoxide, high dose glucocorticoids, adrenergic agents, etc. Subjects will be eligible to participate if the last dose of octreotide is given 48 hrs before study day 1 and the last dose of diazoxide is given 72 hours before study day 1
- •Evidence of a medical condition that might alter results or compromised the elimination of the peptide, including active infection, kidney failure, severe liver dysfunction, severe respiratory or cardiac failure
- •Pregnancy
- •Subjects with milk protein allergy will be excluded for participating in studies involving protein tolerance test
研究组 & 干预措施
Vehicle first, then Exendin-(9-39)
An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). At time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. The following day, at time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, GLP-1, and glucagon will be measured every 30 minutes.
干预措施: Exendin-(9-39) (Drug)
Vehicle first, then Exendin-(9-39)
An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). At time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. The following day, at time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, GLP-1, and glucagon will be measured every 30 minutes.
干预措施: placebo (Drug)
Exendin-(9-39) first then Vehicle.
An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). . At time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. The following day, at time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, GLP-1, and glucagon will be measured every 30 minutes.
.
干预措施: Exendin-(9-39) (Drug)
Exendin-(9-39) first then Vehicle.
An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). . At time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. The following day, at time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, GLP-1, and glucagon will be measured every 30 minutes.
.
干预措施: placebo (Drug)
结局指标
主要结局
Area Under the Curve (AUC) Plasma Glucose
时间窗: Time 0 min - time 360 min
Area under the curve plasma glucose from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion
次要结局
- Area Under the Curve (AUC) Plasma Insulin(time 0 min to time 360 min)
- Area Under the Curve (AUC) Plasma C-peptide(time 0 min to time 360 min)
- Area Under the Curve (AUC) Plasma Glucagon(time 0 min to time 360 min)
- Area Under the Curve ( AUC) Plasma Total GLP-1 (Glucagon-like Peptide-1)(time 0 to time 360 min)
- Area Under the Curve ( AUC) Plasma Active GLP-1 (Glucagon-like Peptide-1)(time 0 min to time 360 min)
研究者
Diva De Leon
M.D. Assistant Professor of Pediatrics
Children's Hospital of Philadelphia