Sitagliptin and Endothelial Dysfunction

NCT ID: NCT02406950

Last Updated: 2015-04-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2015-08-31

Brief Summary

Over the years, numbers of cardioprotective drugs have been evaluated to attenuate lethal ischemia-reperfusion (IR) injuries. There is little study whether sitagliptin protects against endothelial dysfunction induced by IR injury in humans.

Detailed Description

Glucagon-like peptide-1 (GLP-1) is a novel insulinotropic peptide which is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4). In addition to its attractive merit in type 2 diabetes, interest in the cardioprotective effects of GLP-1 has been increased with various reports and evidence. Previously, the investigators could show exenatide, GLP-1 receptor agonist protects ischemic/reperfusion injury-induced endothelial dysfunction through opening of KATP (ATP-sensitive potassium) channels in human ischemic/reperfusion injury model. But, recent clinical studies showed 2 different DPP-4 inhibitors, alogliptin and saxagliptin, did not decrease major adverse cardiovascular events even though improving glycemic control. The investigators will investigate the role of sitagliptin in human ischemic/reperfusion (IR) injury model of forearm conductance vessels as previous described method.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Sitagliptin

All participant will exam brachial artery endothelium-dependent flow-mediated dilatation (FMD). After then, pneumatic cuff wiil be inflated to 200 mmHg for 15 minutes to induce brachial artery ischemia. At the end of ischemia, 15 minutes of reperfusion was performed to induce reperfusion injury. After ischemia-reperfusion (IR) injury, brachial artery FMD will be measured again. After randomization, sitagliptin group will be treated by single dose of sitagliptin (Januvia) 50mg. In 2 hours later, brachial artery FMD measurement, IR injury and brachial artery FMD measurement will be measured again.

Group Type: EXPERIMENTAL

Sitagliptin

Intervention Type: DRUG

The brachial FMD before and after IR injury will be assessed. After randomization, study medication will be treated. In 2 hours later, the brachial FMD before and after IR injury will be assessed again. All volunteers had a wash-out period of 7 days. Seven days later, the subjects returned to crossover study medication (ie, sitagliptin or placebo), and the protocol described above was repeated.

Placebo

After brachial artery FMD measurement, IR injury for each 15 minutes will be performed, and brachial artery FMD will be measured again. After randomization, placebo group will be treated by nothing. In 2 hours later, brachial artery FMD measurement, IR injury and brachial artery FMD measurement will be measured again.

Group Type: PLACEBO_COMPARATOR

No interventions assigned to this group

Sitagliptin and glibenclimide

If sitagliptin treatment show preventive effects of IR injury, the investigator will perform additional experiment to explore the mechanism (Protocol 2 study). Additional 15 healthy volunteers will be treated 5 mg of glibenclamide (Euglucon) 1 hour before administration of 50 m g of sitagliptin. In 2 hours after sitagliptin administration, FMD measurement before and after IR injury will be performed as described above.

Group Type: OTHER

Sitagliptin

Intervention Type: DRUG

The brachial FMD before and after IR injury will be assessed. After randomization, study medication will be treated. In 2 hours later, the brachial FMD before and after IR injury will be assessed again. All volunteers had a wash-out period of 7 days. Seven days later, the subjects returned to crossover study medication (ie, sitagliptin or placebo), and the protocol described above was repeated.

Interventions

Sitagliptin

The brachial FMD before and after IR injury will be assessed. After randomization, study medication will be treated. In 2 hours later, the brachial FMD before and after IR injury will be assessed again. All volunteers had a wash-out period of 7 days. Seven days later, the subjects returned to crossover study medication (ie, sitagliptin or placebo), and the protocol described above was repeated.

Intervention Type: DRUG

Other Intervention Names

Januvia

Eligibility Criteria

Inclusion Criteria

• healthy volunteer age 20 to 40 years
• non-smoker

Exclusion Criteria

• High blood pressure (>140/90 mmHg) or any antihypertensive medications
• diabetes
• any cardiovascular disease
• kidney disease
• thyroid disease
• cerebrovascular disease
• liver disease (bilirubin level >2 mg/dl)
• pregnancy
• body mass index >25 kg/m2

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Kyunghee University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Weon Kim

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Weon Kim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Kyunghee University Medical Center

Locations

Kyung Hee University Hospital

Seoul, Seoul, South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Weon Kim, MD, PhD

Role: CONTACT

mylovekw@hanmail.net

82-2-958-8170

Jong Shin Woo, MD, PhD

Role: CONTACT

snowball77@hanmail.net

82-2-958-8176

Facility Contacts

Weon Kim, MD, PhD

Role: primary

mylovekw@hanmail.net

2-958-8170 ext. 82

Jong Shin Woo, MD

Role: backup

snowball77@hanmail.net

2-958-8176 ext. 82

Other Identifiers

Signal

Identifier Type: -

Identifier Source: org_study_id