Sitagliptin and Endothelial Dysfunction

Kyung Hee University

Status and phase: Unknown; Phase 3

Conditions: Healthy

Treatments: Drug: Sitagliptin

Study type: Interventional

Funder types: Other

Identifiers

NCT02406950

Signal

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 estimated patients

Sex: All

Ages: 20 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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10 participants in 3 patient groups, including a placebo group

Sitagliptin

Experimental group

Description:

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.

Treatment:

Drug: Sitagliptin

Placebo

Placebo Comparator group

Description:

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.

Sitagliptin and glibenclimide

Other group

Description:

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.

Treatment:

Drug: Sitagliptin