NCT02639637

Effect of DPP4 Inhibition on Vasoconstriction

Contribution of Neuropeptide Y (NPY) to Vasoconstriction and Sympathetic Activation in the Setting of Dipeptidyl Peptidase IV (DPP4) Inhibition

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Vanderbilt University · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to understand how dipeptidyl peptidase IV (DPP4) inhibition in diabetics affects hemodynamic parameters and sympathetic activation in the setting of increasing concentrations of neuropeptide Y, an endogenous peptide. The central hypothesis is that DPP4 inhibition decreases degradation of neuropeptide Y, resulting in increased vasoconstriction and sympathetic activation.

Detailed description

Dipeptidyl peptidase IV (DPP4) inhibitors are routinely used for the treatment of type II diabetes mellitus (T2DM). Since the prevalence of hypertension is 1.5-3 times greater in diabetics compared to sex-aged matched controls, the use of antihypertensives such as ACE inhibitors is also common in diabetics. DPP4 is involved in the degradation of multiple vasoactive peptides, one of which is neuropeptide Y. This peptide is thought to play a role in blood pressure regulation and sympathetic nervous system activation. The aim of this study is to investigate how DPP4 inhibition affects vasoconstriction in response to increasing neuropeptide Y concentrations. Additionally, the investigators want to understand how the combination of DPP4 inhibition and ACE inhibition affects vasoconstriction and sympathetic activation. Understanding the hemodynamic and neurohumoral changes associated with DPP4 and ACE inhibitors has important implications for the millions of patients with T2DM who take these drugs concurrently.

Conditions

• Type 2 Diabetes Mellitus

Interventions

Type	Name	Description
DRUG	Sitagliptin	Subjects will receive sitagliptin 100 mg daily for 7 days prior to one of the study days.
DRUG	Placebo	Subjects will receive a placebo capsule daily for 7 days prior to one of the study days.
DRUG	Neuropeptide Y	During the study days, neuropeptide Y will be infused through an intra-arterial line. There will be four doses of neuropeptide Y used (0.1, 0.3, 1.0, and 3.0 nmol/min) and each dose will be infused for 10 minutes.
DRUG	Enalaprilat	Ninety minutes after the last dose of neuropeptide Y, enalaprilat will be infused through the intra-arterial line at 0.33 µg/min/100mL of forearm volume. After 30 minutes, a second infusion of neuropeptide Y will begin. Similar to the previous neuropeptide infusion, four doses of neuropeptide Y will be used (0.1, 0.3, 1.0, and 3.0 nmol/min) and each dose will be infused for 10 minutes.
DRUG	Valsartan 160mg	Valsartan 160 mg/d for 7 days prior to one of the study days.

Timeline

• Start date: 2015-12-01
• Primary completion: 2017-06-01
• Completion: 2017-09-01
• First posted: 2015-12-24
• Last updated: 2018-08-27
• Results posted: 2018-08-27

Locations

1 site across 1 country: United States