Study on Exploring the Effect of DPP-4 Inhibitors on β-cell Function by Using the Two-step Hyperglycemic Clamp

Type 2 Diabetes Clinical Trial

Official title: 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

Status Recruiting

Clinical Trial Summary

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.

Clinical Trial Description

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. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Type 2 Diabetes

• NCT number: NCT02386943
• Study type: Interventional
• Source: Shanghai Jiao Tong University School of Medicine
• Contact: Guang Ning, MD. PHD
• Phone: +86021-64370045
• Status: Recruiting
• Phase: Phase 4
• Start date: December 2013
• Completion date: March 2015