Effect of Chronic ACE and DPP4 Inhibition on Blood Pressure

• Status: Completed
• Trial end date: 2020-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University
• Treatments: Angiotensin-Converting Enzyme Inhibitors; Aprepitant; Dipeptidyl-Peptidase IV Inhibitors; Fosaprepitant; Ramipril; Sitagliptin Phosphate

Criteria

Inclusion Criteria:

Age 18 to 80 years old

For female subjects the following conditions must be met:

Postmenopausal status for at least 1 year, or Status-post surgical sterilization, or If of childbearing potential, utilization of barrier methods of birth control and willingness to undergo urine β-HCG testing prior to drug treatment and on every study day

T2DM, as defined by 1 or more of the following at the time of screening visit:

• Hgb A1C ≥6.5%, or

• Fasting plasma glucose ≥126mg/dL, or

• 2-hour plasma glucose ≥200 mg/dL following 75gr oral glucose load

Hypertension, as defined by:

• Seated SBP ≥130 mm Hg on three occasions documented in medical record, or

• Seated DBP ≥80 mm Hg on three occasions documented in medical record, or

• Treatment with antihypertensive medications for a minimum of 6 months

Exclusion Criteria:

• Type 1 diabetes

• Poorly controlled T2DM, defined as Hgb A1C>8.7%

• Use of anti-diabetic medications other than metformin for at least 12 months prior to initiation of the study

• Secondary hypertension

• Subjects who have participated in a weight-reduction program during the last 6 months and whose weight has increased or decreased more than 5 kg over the preceding 6 months

• Pregnancy

• Breast-feeding

• Treatment with drugs primarily metabolized through CYP3A4 (e.g. cisapride, pimozide)

• Clinically significant gastrointestinal impairment that could interfere with drug absorption

• Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy and diastolic dysfunction acceptable), deep vein thrombosis, pulmonary embolism, second- or third-degree AV block, mitral valve stenosis, or hypertrophic cardiomyopathy

• Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino transaminase [ALT] >3 x upper limit of normal range)

• Impaired renal function (eGFR< 50mL/min/1.73m2 as determined by the MDRD equation)

• History or presence of immunological or hematological disorders.

• History of pancreatitis or know pancreatic lesion

• History of angioedema while taking an ACE inhibitor

• Hematocrit <35%

• Treatment with anticoagulants

• Diagnosis of asthma requiring use of inhaled β-2 agonist more than 1 time per week

• Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult

• Treatment with systemic glucocorticoids within the last 6 months

• Treatment with lithium salts

• Treatment with any investigational drug in the 1 month preceding the study

• Mental conditions rendering the subject unable to understand the nature, scope, or possible consequences of the study

• Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study