Renin Angiotensin Aldosterone System (RAAS) and Fibrinolysis in Humans: ACEi and PE5i
Not Applicable
Completed
- Conditions
- Metabolic Syndrome
- Interventions
- Registration Number
- NCT00750308
- Lead Sponsor
- Vanderbilt University
- Brief Summary
This study will measure the effect of the agent tadalafil on glucose and insulin homeostasis in people with metabolic syndrome in the presence and absence of an ACE inhibitor.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 27
Inclusion Criteria
-
Ambulatory subjects, 18 to 70 years of age, inclusive
-
For female subjects, the following conditions must be met:
- Postmenopausal status for at least 1 year,
- Status-post surgical sterilization, or
- If of childbearing potential, utilization of adequate birth control, and willingness to undergo urine beta-hcg testing prior to drug treatment and on every study day
-
Metabolic syndrome as defined by 3 or more of the following:
- Fasting plasma glucose of at least 100 mg/dL (5.5 mmol/L),
- Serum triglycerides of at least 150 mg/dL (1.7 mmol/L),
- Serum HDL cholesterol less than 40 mg/dL (1.04 mmol/L) in males and less than 50mg/dl (1.30mmol/L) in females,
- Blood pressure of at least 130/85 mmHg, or
- Waist girth of more than 102 cm in men or 88 cm in women
Exclusion criteria:
Subjects presenting with any of the following will not be included in the study:
- Diabetes type 1 or type 2, as defined by a fasting glucose of 126 mg/dL or greater or the use of anti-diabetic medication
- Use of hormone replacement therapy
- Statin therapy
- In hypertensive subjects, a seated systolic blood pressure greater than 179 mmHg or a seated diastolic blood pressure greater than 110 mmHg
- Pregnancy
- Breast-feeding
- Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, 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
- Treatment with anticoagulants
- History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack
- History or presence of immunological or hematological disorders
- Diagnosis of asthma
- Clinically significant gastrointestinal impairment that could interfere with drug absorption
- Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino transaminase [ALT] > 1.5 x upper limit of normal range)
- Impaired renal function (serum creatinine > 1.5 mg/dl)
- Hematocrit < 35%
- 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 chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
- Treatment with lithium salts
- 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 for follow-up visits, and unlikelihood of completing the study
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description tadalafil, ramapril, combo, placebo placebo placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, ramipril + tadalafil, washout, placebo+placebo for three weeks tadalafil, placebo, ramipril, combo Tadalafil placebo+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+ramipril for three weeks, washout, ramipril+tadalafil for three weeks ramipril, combo, tadalfil, placebo placebo placebo+ramipril for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo for three weeks combo, placebo, tadalafil, ramipril Ramipril ramipril+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks tadalafil, combo, placebo, ramipril Ramipril placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+ramipril for three weeks tadalafil, ramapril, combo, placebo Tadalafil placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, ramipril + tadalafil, washout, placebo+placebo for three weeks combo, tadalafil, ramipril, placebo Tadalafil ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+placebo for three weeks ramipril, tadalafil, placebo, combo placebo placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks combo, placebo, tadalafil, ramipril placebo ramipril+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks tadalafil, placebo, ramipril, combo placebo placebo+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+ramipril for three weeks, washout, ramipril+tadalafil for three weeks ramipril, combo, tadalfil, placebo Ramipril placebo+ramipril for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo for three weeks combo, ramipril, placebo, tadalafil placebo ramipril+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks tadalafil, combo, placebo, ramipril placebo placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+ramipril for three weeks placebo, combo, ramipril, tadalafil Tadalafil placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks, washout placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks placebo, combo, ramipril, tadalafil placebo placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks, washout placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks combo, ramipril, placebo, tadalafil Tadalafil ramipril+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks combo, tadalafil, ramipril, placebo placebo ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+placebo for three weeks placebo, ramipril, tadalafil, combo placebo placebo+placebo for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks placebo, tadalafil, combo, ramipril placebo placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+ramipril for three weeks ramipril, placebo, combo, tadalafil placebo placebo+ramipril for three weeks, washout, placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks placebo, ramipril, tadalafil, combo Ramipril placebo+placebo for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks combo, tadalafil, ramipril, placebo Ramipril ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+placebo for three weeks tadalafil, ramapril, combo, placebo Ramipril placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, ramipril + tadalafil, washout, placebo+placebo for three weeks ramipril, tadalafil, placebo, combo Ramipril placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks ramipril, tadalafil, placebo, combo Tadalafil placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks combo, placebo, tadalafil, ramipril Tadalafil ramipril+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks placebo, combo, ramipril, tadalafil Ramipril placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks, washout placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks tadalafil, placebo, ramipril, combo Ramipril placebo+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+ramipril for three weeks, washout, ramipril+tadalafil for three weeks ramipril, combo, tadalfil, placebo Tadalafil placebo+ramipril for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo for three weeks combo, ramipril, placebo, tadalafil Ramipril ramipril+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks placebo, tadalafil, combo, ramipril Ramipril placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+ramipril for three weeks placebo, tadalafil, combo, ramipril Tadalafil placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+ramipril for three weeks tadalafil, combo, placebo, ramipril Tadalafil placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+ramipril for three weeks ramipril, placebo, combo, tadalafil Ramipril placebo+ramipril for three weeks, washout, placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks ramipril, placebo, combo, tadalafil Tadalafil placebo+ramipril for three weeks, washout, placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks placebo, ramipril, tadalafil, combo Tadalafil placebo+placebo for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks
- Primary Outcome Measures
Name Time Method Beta Cell Function 3 hours Beta cell function as measured during a frequently sampled IV glucose tolerance test
Insulin Sensitivity three weeks As assessed using IV glucose tolerance test and calculated using Min Mod units mU/mm
- Secondary Outcome Measures
Name Time Method