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

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ClinicalTrials.gov Identifier: NCT01660386
Recruitment Status : Unknown
Verified December 2012 by Guang Ning, Shanghai Jiao Tong University School of Medicine.
Recruitment status was:  Recruiting
First Posted : August 8, 2012
Last Update Posted : December 17, 2012
Sponsor:
Information provided by (Responsible Party):
Guang Ning, Shanghai Jiao Tong University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Drug: Sitagliptin Drug: Saxagliptin Drug: Glimepiride Drug: Blank control Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Official Title: An Open-label, Randomized, Four-way Cross-over, Single Dose Study to Compare the Different Effect of DPP-4 Inhibitors and Sulfonylurea on the Beta Cell Function by Using "Biphase-Hyperglycemic Clamp"
Study Start Date : July 2012
Estimated Primary Completion Date : December 2012
Estimated Study Completion Date : March 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Saxagliptin

Arm Intervention/treatment
Experimental: 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.
Drug: Sitagliptin
100mg po once
Other Name: Januvia

Experimental: 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.
Drug: Saxagliptin
5mg po once
Other Name: Onglyza

Experimental: 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.
Drug: Glimepiride
2mg po once
Other Name: Amaryl

Blank control
the subjects take no medication at experimental day and start bi-phase hyperglycaemic clamp at 9am.
Drug: Blank control
the subjects take no medication at experimental day and start bi-phase hyperglycaemic clamp at 9am.
Other Name: Baseline




Primary Outcome Measures :
  1. The acute phase and second phase of insulin secretion and C peptide secretion [ Time Frame: 1-2 months ]
    The primary outcome measures are improvement in beta cell function measured as insulin secretion and C-peptide secretion during the bi-phase hyperglycaemic clamp. The first phase of insulin and C-peptide secretion is defined as the secretion between 0-10min, the second phase is defined as secretion between 20-90min of bi-phase hyperglycaemic clamp


Secondary Outcome Measures :
  1. Alpha cell function,GLP-1 response [ Time Frame: 1-2 months ]
    The secondary outcome measures are a relative increase in glucagon concentration which indicates alpha cell function and the GLP-1 response, DPP-4 activity and before taken the medicine and in 0, 10, 90,150,160,240min during the bi-phase hyperglycaemic clamp.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 30 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01660386


Contacts
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Contact: Guang Ning, MD. PHD +8621-64370045 ext 665340 guangning@medmail.com.cn

Locations
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China
Shanghai Jiao Tong University School of Medicine Recruiting
Shanghai, China, 200021
Contact: Guang Ning, MD,PHD    +8621-64370045 ext 665340    guangning@medmail.com.cn   
Principal Investigator: Guang Ning, MD,PHD         
Sponsors and Collaborators
Shanghai Jiao Tong University School of Medicine
Investigators
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Principal Investigator: Guang Ning, MD. PHD Shanghai Jiao Tong University School of Medicine

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Responsible Party: Guang Ning, the vice-president of Shanghai Jiao Tong University affiliated Rui jin Hospital, Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier: NCT01660386     History of Changes
Other Study ID Numbers: CCEMD014
First Posted: August 8, 2012    Key Record Dates
Last Update Posted: December 17, 2012
Last Verified: December 2012

Keywords provided by Guang Ning, Shanghai Jiao Tong University School of Medicine:
Type 2 Diabetes
Dpp-4 inhibitor
Sulfonylurea
beta cell function

Additional relevant MeSH terms:
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Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin Phosphate
Glimepiride
Saxagliptin
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Immunosuppressive Agents
Immunologic Factors