Healthy
Conditions
Keywords
Sitagliptin, Endothelium, Ischemia-Reperfusion Injury, human
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.
Interventions
DRUGSitagliptin
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.
Sponsors
Kyunghee University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 3 weeks | Adverse events such as hypoglycemia |
Countries
South Korea
Contacts
Primary ContactWeon Kim, MD, PhD
Backup ContactJong Shin Woo, MD, PhD
Outcome results
None listed