Effect of DPP4 Inhibition on Vasoconstriction
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Sitagliptin; Placebo; Neuropeptide Y; Enalaprilat; Valsartan 160mg
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Subjects will receive sitagliptin 100 mg daily for 7 days prior to one of the study days.; Subjects will receive a placebo capsule daily for 7 days prior to one of the study days.; 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.; 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.; Valsartan 160 mg/d for 7 days prior to one of the study days.
Other intervention name(s): Januvia; Microcrystalline cellulose; NPY; Vasotec I.V.; valsartan p.o.
Intervention MeSH terms: Sitagliptin Phosphate; Valsartan; Enalaprilat; Enalapril
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Crossover Arms 1 and 2, Crossover Arms 3 and 4
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Type 2 Diabetes Mellitus; Sitagliptin; Dipeptidyl Peptidase IV Inhibitors; Angiotensin Converting Enzyme Inhibitors; Enalaprilat; Neuropeptide Y