Renin Angiotensin Aldosterone System (RAAS) and Fibrinolysis in Humans: ACEi
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Vanderbilt University
- Enrollment
- 27
- Primary Endpoint
- Beta Cell Function
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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
Arms & Interventions
tadalafil, ramapril, combo, placebo
placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, ramipril + tadalafil, washout, placebo+placebo for three weeks
Intervention: Ramipril (Drug)
tadalafil, ramapril, combo, placebo
placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, ramipril + tadalafil, washout, placebo+placebo for three weeks
Intervention: Tadalafil (Drug)
tadalafil, ramapril, combo, placebo
placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, ramipril + tadalafil, washout, placebo+placebo for three weeks
Intervention: placebo (Drug)
ramipril, tadalafil, placebo, combo
placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks
Intervention: Ramipril (Drug)
ramipril, tadalafil, placebo, combo
placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks
Intervention: Tadalafil (Drug)
ramipril, tadalafil, placebo, combo
placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks
Intervention: placebo (Drug)
combo, placebo, tadalafil, ramipril
ramipril+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks
Intervention: Ramipril (Drug)
combo, placebo, tadalafil, ramipril
ramipril+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks
Intervention: Tadalafil (Drug)
combo, placebo, tadalafil, ramipril
ramipril+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks
Intervention: placebo (Drug)
placebo, combo, ramipril, tadalafil
placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks, washout placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks
Intervention: Ramipril (Drug)
placebo, combo, ramipril, tadalafil
placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks, washout placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks
Intervention: Tadalafil (Drug)
placebo, combo, ramipril, tadalafil
placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks, washout placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks
Intervention: placebo (Drug)
tadalafil, placebo, ramipril, combo
placebo+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+ramipril for three weeks, washout, ramipril+tadalafil for three weeks
Intervention: Ramipril (Drug)
tadalafil, combo, placebo, ramipril
placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+ramipril for three weeks
Intervention: placebo (Drug)
tadalafil, placebo, ramipril, combo
placebo+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+ramipril for three weeks, washout, ramipril+tadalafil for three weeks
Intervention: Tadalafil (Drug)
tadalafil, placebo, ramipril, combo
placebo+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+ramipril for three weeks, washout, ramipril+tadalafil for three weeks
Intervention: placebo (Drug)
ramipril, combo, tadalfil, placebo
placebo+ramipril for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo for three weeks
Intervention: Ramipril (Drug)
ramipril, combo, tadalfil, placebo
placebo+ramipril for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo for three weeks
Intervention: Tadalafil (Drug)
ramipril, combo, tadalfil, placebo
placebo+ramipril for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo for three weeks
Intervention: placebo (Drug)
placebo, tadalafil, combo, ramipril
placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+ramipril for three weeks
Intervention: Ramipril (Drug)
combo, ramipril, placebo, tadalafil
ramipril+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks
Intervention: Ramipril (Drug)
combo, ramipril, placebo, tadalafil
ramipril+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks
Intervention: Tadalafil (Drug)
combo, ramipril, placebo, tadalafil
ramipril+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks
Intervention: placebo (Drug)
placebo, tadalafil, combo, ramipril
placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+ramipril for three weeks
Intervention: Tadalafil (Drug)
placebo, tadalafil, combo, ramipril
placebo+placebo for three weeks, washout, placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+ramipril for three weeks
Intervention: placebo (Drug)
tadalafil, combo, placebo, ramipril
placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+ramipril for three weeks
Intervention: Ramipril (Drug)
tadalafil, combo, placebo, ramipril
placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+placebo for three weeks, washout, placebo+ramipril for three weeks
Intervention: Tadalafil (Drug)
ramipril, placebo, combo, tadalafil
placebo+ramipril for three weeks, washout, placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks
Intervention: Ramipril (Drug)
ramipril, placebo, combo, tadalafil
placebo+ramipril for three weeks, washout, placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks
Intervention: Tadalafil (Drug)
ramipril, placebo, combo, tadalafil
placebo+ramipril for three weeks, washout, placebo+placebo for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks
Intervention: placebo (Drug)
combo, tadalafil, ramipril, placebo
ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+placebo for three weeks
Intervention: Ramipril (Drug)
combo, tadalafil, ramipril, placebo
ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+placebo for three weeks
Intervention: Tadalafil (Drug)
combo, tadalafil, ramipril, placebo
ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+placebo for three weeks
Intervention: placebo (Drug)
placebo, ramipril, tadalafil, combo
placebo+placebo for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks
Intervention: Ramipril (Drug)
placebo, ramipril, tadalafil, combo
placebo+placebo for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks
Intervention: Tadalafil (Drug)
placebo, ramipril, tadalafil, combo
placebo+placebo for three weeks, washout, placebo+ramipril for three weeks, washout, placebo+tadalafil for three weeks, washout, ramipril+tadalafil for three weeks
Intervention: placebo (Drug)
Outcomes
Primary Outcomes
Beta Cell Function
Time Frame: 3 hours
Beta cell function as measured during a frequently sampled IV glucose tolerance test
Insulin Sensitivity
Time Frame: three weeks
As assessed using IV glucose tolerance test and calculated using Min Mod units mU/mm
Secondary Outcomes
No secondary outcomes reported
Investigators
Nancy J. Brown
Professor of Medicine
Vanderbilt University