NCT02130687

Effect of Chronic ACE and DPP4 Inhibition on Blood Pressure

Contribution of Substance P to Blood Pressure Regulation in the Setting of Dipeptidyl Peptidase IV (DPP4) and Angiotensin-Converting Enzyme (ACE) Inhibition

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 106 (actual)
• Sponsor: Vanderbilt University · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

In this study the investigators will test the hypothesis that dipeptidyl peptidase IV (DPP4) inhibition attenuates the antihypertensive effect of angiotensin-converting enzyme (ACE) inhibition but not angiotensin receptor blockade or calcium channel blockade. The investigators further hypothesize that this effect is mediated by substance P.

Detailed description

The use of dipeptidyl peptidase IV (DPP4) inhibitors for the treatment of type 2 diabetes (T2DM) is growing rapidly. The majority of patients with T2DM are also taking ACE inhibitors or angiotensin receptor blockers (ARBs) in order to reduce cardiovascular and renal morbidity and mortality. DPP4 and ACE inhibitors share the common vasoactive substrate substance P. Substance P acts as a vasodilator but also activates the sympathetic nervous system. Understanding the interactive effects of DPP4 and ACE inhibitors on blood pressure and neurohumoral activation has important implications for the millions of patients with T2DM who take these drugs concurrently.

Conditions

• Type 2 Diabetes Mellitus
• Hypertension

Interventions

Type	Name	Description
DRUG	Placebo	Subjects will receive two capsules of placebo to preserve the blinding of the study. In a separate period, subjects will receive one capsule of placebo and one capsule of sitagliptin.
DRUG	Sitagliptin	Subjects will receive sitagliptin 100mg daily for 7 days. In addition, subjects will receive either aprepitant or a capsule of placebo to preserve the blinding of the study.
DRUG	Aprepitant	Subjects will receive aprepitant (125 mg on the first day followed by 80mg/d) for 7 days along with sitagliptin.
OTHER	Mixed Meal Test (MMT)	The first 18 subjects per arm/ group will undergo a mixed meal test on the 7th day of each medication intervention. This will take place after the first half of the study day at the clinical research center, following a 30 minute rest. Subjects will ingest a shake (combination of fixed carbohydrates/ fat/ protein) and have blood pressure, heart rate, and venous blood sample measurements collected for 4 hours after the meal.

Timeline

• Start date: 2014-06-01
• Primary completion: 2020-05-01
• Completion: 2020-08-01
• First posted: 2014-05-05
• Last updated: 2022-03-02
• Results posted: 2021-07-26

Locations

1 site across 1 country: United States