Pharmacogenetics of Ace Inhibitor-Associated Angioedema
Hypertension, Diabetes Type 2
About this trial
This is an interventional treatment trial for Hypertension focused on measuring DPPIV inhibitors, ACE inhibitors, Bradykinin, glucagon-like peptide (GLP-1), BNP, diabetes, hypertension
Eligibility Criteria
Inclusion Criteria:
- Age 18 to 65 inclusive
- Men and women
- Black and White Americans
- BMI <25
For female subjects:
- Postmenopausal status for at least 1 year
- Status post surgical sterilization
- If childbearing potential, utilization of a barrier method of birth control and willingness to undergo blood B-hcg testing prior to drug treatment and on every study day
Exclusion Criteria:
- Smoking
- Diabetes type 1 or 2, as defined by a fasting glucose of 126 mg/dl or greater or the use of anti-diabetic medication
- Hypertension as defined by an untreated seated SBP greater than 140 mmHg an untreated DBP greater than 90 mmHg or the use of antihypertensives
- History of reported or recorded hypoglycemia (plasma glucose less than 70 mg/dl)
- Pregnancy
- Breast-feeding
- Use of hormone replacement therapy
- The use of contraceptive therapy
- Use of any medication other than multivitamin
- Hematocrit <35%
- Cardiovascular disease such as history of myocardial infarction, presence of angina pectoris, significant arrhythmia, congestive heart failure(LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
- Asthma
- History of angioedema
- History of cough or other side effect during ACE inhibitor use
- Impaired renal function, as defined by an eGFR<60ml/min/1.73M2
- Clinically significant gastrointestinal impairment that could interfere with drug absorption
- Impaired hepatic function (aspartate amino transaminase[AST] and/or alanine amino transferase [ALT]>2 x upper limit of normal range
- History of alcohol or drug abuse
- Treatment with any investigational drug in the 1 month preceding the study
- Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
- Inability to comply with the protocol, e.g., uncooperative attitude, inability to return to follow-up visits, and the unlikelihood of completing the study
Sites / Locations
- Vanderbilt University- General Clinic Research Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Placebo Comparator
Placebo Comparator
Placebo Comparator
Placebo Comparator
Placebo then sitagliptin (DPP4 inhibition) group 1
Sitagliptin (DPP4 inhibition) then placebo group 1
Placebo then sitagliptin group 2
Sitagliptin (DPP4 inhibition) then comparator group 2
The effect of vehicle and enalaprilat on the forearm blood flow and t-PA responses to bradykinin and substance P are studied after administration of placebo or sitagliptin (DPP4 inhibition).
The effect of vehicle and enalaprilat (ACE inhibition) on the forearm blood flow and t-PA responses to substance P and bradykinin are studied after administration of sitagliptin (DPP4 inhibition) or placebo
The effect of vehicle and enalaprilat (ACE inhibition) on the forearm blood flow and t-PA responses to glucagon-like peptide-1 and brain natriuretic pepdie are studied after administration of placebo or sitagliptin (DPP4 inhibition).
The effect of vehicle and enalaprilat on the forearm blood flow and t-PA responses to glucagon-like peptide and brain natriuretic peptide are studied after administration of placebo or sitagliptin (DPP4 inhibition).