Study of Comparing the Different Effect of DPP-4 Inhibitors and Sulfonylurea by Using "Biphase-Hyperglycemic Clamp"

NCT ID: NCT01660386

Last Updated: 2012-12-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2013-03-31

Brief Summary

The objective of this study is to demonstrate the different effects of two DPP-4 inhibitors(Sitagliptin, Saxagliptin)and the insulin secretagogue: glimepiride on first and second phase insulin secretion by using a Biphase-Hyperglycemic Clamp and to explore the different effects of the study drugs on the GLP-1 response, and the glucagon concentration which indicates alpha cell function in healthy subjects.

Detailed Description

After enrollment and two weeks screening period eligible subjects will be counseled to follow a dietary program for approximately 2 wk and recorded of personal history, full clinical examination and screening blood samples.

Subjects will be randomized using a computer-generated allocation schedule to one of 12 sequences during which each subjects will be assigned to take 4 times of bi-phase hyperglycaemic clamp experiments at a randomized sequence separated by a washout period of 7-14d.

At each experimental day, the subject will take the given dose of Sitagliptin, Saxagliptin, Glimepiride 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 (42C) 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 12mM. The glucose bolus will be calculated as:(12mM-FPG)×35 mg glucose × body weight (kg). PG will be measured bedside every 5 min and maintained at 12mM by an adjustable continuous 20% glucose infusion. After 90min, PG will be lowered down below 6mM for the islet cells to rest, then the subject will be instructed to consume 75g glucose solution orally in 5min, PG will be measured bedside every 5 min and maintained below 6mM for 40min then restart the 90min-hyperglycaemic clamp experiment. 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, total GLP-1 and DPP-4 activity.

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, total GLP-1 and DPP-4 activity as well.

Conditions

Type 2 Diabetes

Keywords

Type 2 Diabetes; Dpp-4 inhibitor; Sulfonylurea; beta cell function

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: NONE

Study Groups

Sitagliptin

the subjects are asked to take one pill of sitagliptin(100mg po once) in 7am of experimental day then start bi-phase hyperglycaemic clamp at 9am.

Group Type: EXPERIMENTAL

Sitagliptin

Intervention Type: DRUG

100mg po once

Saxagliptin

the subjects are asked to take one pill of saxagliptin(5mg po once) in 7am of experimental day then start bi-phase hyperglycaemic clamp at 9am.

Group Type: EXPERIMENTAL

Saxagliptin

Intervention Type: DRUG

5mg po once

Glimepiride

the subjects are asked to take one pill of glimepiride(2mg po once) in 7am of experimental day then start bi-phase hyperglycaemic clamp at 9am.

Group Type: EXPERIMENTAL

Glimepiride

Intervention Type: DRUG

2mg po once

Blank control

the subjects take no medication at experimental day and start bi-phase hyperglycaemic clamp at 9am.

Group Type: OTHER

Blank control

Intervention Type: DRUG

the subjects take no medication at experimental day and start bi-phase hyperglycaemic clamp at 9am.

Interventions

Sitagliptin

100mg po once

Intervention Type: DRUG

Saxagliptin

5mg po once

Intervention Type: DRUG

Glimepiride

2mg po once

Intervention Type: DRUG

Blank control

the subjects take no medication at experimental day and start bi-phase hyperglycaemic clamp at 9am.

Intervention Type: DRUG

Other Intervention Names

Januvia; Onglyza; Amaryl; Baseline

Eligibility Criteria

Inclusion Criteria

1. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted;

2. Having good study compliance;

3. Healthy Male subjects between 20-30 years of age (inclusive), and in good health as determined by past medical history, physical examination, vital signs, and clinical laboratory test;

4. Must have a body mass index (BMI) between 19-25kg/m2 (inclusive);

5. No weight fluctuation greater than 5% in late 3 months。

Exclusion Criteria

1. With impaired glucose tolerance, T2DM or any significant medical condition (within 3 years), laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study;

2. Used any prescribed systemic or topical medication within 30 days of the first dose administration;

3. Any medical or surgical conditions possibly affecting study drug absorption, distribution, metabolism and excretion;

4. 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);

5. Donated blood or plasma or had any other significant blood loss within 2 months preceding the first dose administration;

6. History of multiple drug allergies;

7. Any clinically significant allergic disease;

8. 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);

9. Smokers or users of other tobacco products in the 3 months prior to screening.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Guang Ning

the vice-president of Shanghai Jiao Tong University affiliated Rui jin Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Guang Ning, MD. PHD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Jiao Tong University School of Medicine

Locations

Shanghai Jiao Tong University School of Medicine

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Guang Ning, MD. PHD

Role: CONTACT

Phone: +8621-64370045

Email: guangning@medmail.com.cn

Facility Contacts

Guang Ning, MD,PHD

Role: primary

Other Identifiers

CCEMD014

Identifier Type: -

Identifier Source: org_study_id