Clinical trial NCT00750308: Renin Angiotensin Aldosterone System (RAAS) and Fibrinolysis in Humans: ACEi and PE5i
Official title: Renin Angiotensin Aldosterone System (RAAS) and Fibrinolysis in Humans: ACEi
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Lead sponsor: Vanderbilt University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2008-09-10
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

1. Ambulatory subjects, 18 to 70 years of age, inclusive
2. 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
3. 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:

1. 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
2. Use of hormone replacement therapy
3. Statin therapy
4. In hypertensive subjects, a seated systolic blood pressure greater than 179 mmHg or a seated diastolic blood pressure greater than 110 mmHg
5. Pregnancy
6. Breast-feeding
7. 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
8. Treatment with anticoagulants
9. History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack
10. History or presence of immunological or hematological disorders
11. Diagnosis of asthma
12. Clinically significant gastrointestinal impairment that could interfere with drug absorption
13. Impaired hepatic function (aspartate amino transaminase \[AST\] and/or alanine amino transaminase \[ALT\] \> 1.5 x upper limit of normal range)
14. Impaired renal function (serum creatinine \> 1.5 mg/dl)
15. Hematocrit \< 35%
16. 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
17. Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
18. Treatment with lithium salts
19. History of alcohol or drug abuse
20. Treatment with any investigational drug in the 1 month preceding the study
21. Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
22. Inability to comply with the protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study

Primary outcomes:
measure: Beta Cell Function
timeFrame: 3 hours
measure: Insulin Sensitivity
timeFrame: three weeks
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Vanderbilt University Medical Center
name: Nancy J Brown, M.D.
role: PRINCIPAL_INVESTIGATOR
References: