Sitagliptin and Endothelial Dysfunction

Phase 3

• Conditions: Healthy
• Interventions: Drug: Sitagliptin

• Registration Number: NCT02406950
• Lead Sponsor: Kyunghee University Medical Center

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.

Study Timeline

• Study Start: 2015-02
• Status Verified: 2015-03
• Study First Submitted: 2015-03-14
• Study First Submitted QC: 2015-04-01
• Last Update Submitted: 2015-04-01
• Study First Posted: 2015-04-02
• Last Update Posted: 2015-04-02
• Primary Completion: 2015-06
• Study Completion: 2015-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sitagliptin	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.
Sitagliptin and glibenclimide	Sitagliptin	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.

Primary Outcome Measures

Name	Time	Method
The difference of FMD [brachial artery endothelium-dependent flow-mediated dilatation] after IR injury (brachial FMD before and after IR injury will be assessed)	2 hours after study drug treatment

Secondary Outcome Measures

Name	Time	Method
The difference of FMD after IR injury in co-treatment of glibenclimide and sitagliptin ((brachial FMD before and after IR injury will be assessed)	3.5 hours after study drug treatment

Trial Locations

Locations (1)

Kyung Hee University Hospital; 🇰🇷 Seoul, Korea, Republic of