An Open-label, Randomized,Three-way Cross-over, Single Dose Study to Explore the Effect of DPP-4 Inhibitors on β-cell Function by Using the Two-step Hyperglycemic Clamp
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- β-cell function (measurement of insulin and c-peptide during the clamp study)
研究概览
简要总结
The objective of this study is to explore the effects of two DPP-4 inhibitors(Sitagliptin, Saxagliptin) on β- and α-cell function, as well as the incretin effect.
详细描述
The study is an open-label, randomized, three-way crossover and single-dose study.Subjects with newly onset T2DM are enrolled. They are assigned to take a single dose of sitagliptin (100 mg), saxagliptin (5 mg), or blank control in a randomized order separated by a washout period of 7-14 days.Then the two-step hyperglycemic clamp is initiated.
On each experimental day, the subject will take the given dose of Sitagliptin, Saxagliptin and nothing for blank control two hours before the clamp experiment starts.
The hyperglycaemic clamp will be performed after an overnight fast. Subjects will be placed in a recumbent position and cannula will be inserted in a dorsal hand vein. The hand will be placed in a heating box (50℃) throughout the experiment to allow frequent sampling of arterialized blood. A second cannula will be inserted in a contralateral cubital vein for glucose infusion.
At time zero (0 min), a 50% glucose bolus will be injected during 1 min to increase PG to 15mM. The glucose bolus will be calculated as:(15mM-FPG)×35 mg glucose × body weight (kg). PG will be measured bedside every 5 min and maintained at 15mM by an adjustable continuous 20% glucose infusion. After 90min, PG will be lowered down to 7mM for the islet cells to rest, then the subject will be instructed to consume 75g glucose solution orally in 5min. 40min after the oral glucose consumption, the 90min-hyperglycaemic clamp experiment wil be restarted. The oral period of hyperglycaemic clamp process is the same as what's done in fasting period. Blood samples will be collected in -2h, 0min, 10min, 90min in both hyperglycaemic clamp experimental process for the measurement of insulin, c-peptide, glucagon, active GLP-1 and other incretin hormones.
Thus we could evaluate the beta cell function represented by the first phase and the second phase of insulin secretion(C-peptide secretion) and alpha cell function represented by the change of glucagon concentration during the fasting period and oral period of hyperglycaemic clamp experiment and the change of active GLP-1.
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
- 40 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •40-60 years old;
- •Diagnosed as T2DM according to the 1999 World Health Organization criteria within 2 years;
- •Free of any antihypoglycemia therapy ever;
- •No weight fluctuation greater than 5% in late 3 months.
- •Understand and voluntarily sign an informed consent document.
- •Good study compliance.
排除标准
- •With any significant medical condition (within 3 years), laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study;
- •Used any prescribed systemic or topical medication within 30 days of the first dose administration;
- •Any medical or surgical conditions possibly affecting study drug absorption, distribution, metabolism and excretion;
- •Participated in a clinical study involving administration of an investigational drug within 90 days preceding the first dose administration or within five half-lives of the first dose administration (whichever is longer);
- •Donated blood or plasma or had any other significant blood loss within 2 months preceding the first dose administration;
- •History of multiple drug allergies;
- •Any clinically significant allergic disease;
- •Recently drug or alcohol abuse (>35 unit/week, 1 unit=8g alcohol @ 1 standard drink @ 250ml beer @ 140ml wine @ 25ml strong alcohol drink like whiskey); Smokers or users of other tobacco products in the 3 months prior to screening.
研究组 & 干预措施
Sitagliptin
Subjects are assigned to take one pill of sitagliptin(100mg po once) at 7am on experimental day,then the two-step hyperglycaemic clamp is initiated at 9am.
干预措施: Sitagliptin (Drug)
Saxagliptin
Subjects are assigned to take one pill of saxagliptin(5mg po once) at 7am on experimental day,then the two-step hyperglycaemic clamp is initiated at 9am.
干预措施: Saxagliptin (Drug)
Blank control
Subjects take no medication for blank control at experimental day,then the two-step hyperglycaemic clamp is initiated at 9am.
干预措施: Blank control (Drug)
结局指标
主要结局
β-cell function (measurement of insulin and c-peptide during the clamp study)
时间窗: 15 months
The primary endpoints are the effects of DPP-4 inhibitors on β-cell function, with the measurement of insulin and c-peptide during the clamp study.
次要结局
- α-cell function (measurement of glucagon during the clamp study)(15 months)
- Incretin effect (measurement of active GLP-1 during the clamp study)(15 months)
研究者
Guang Ning
the vice-president of Shanghai Jiao Tong University Affiliated Ruijin Hospital
Shanghai Jiao Tong University School of Medicine