Renin Angiotensin Aldosterone System (RAAS) and Fibrinolysis in Humans: ACEi and PE5i

This study has been completed.
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00750308
First received: September 5, 2008
Last updated: December 8, 2014
Last verified: December 2014
  Purpose
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.

Condition Intervention
Metabolic Syndrome
Drug: Ramipril
Drug: Tadalafil
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Renin Angiotensin Aldosterone System (RAAS) and Fibrinolysis in Humans: ACEi

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Beta Cell Function [ Time Frame: 3 hours ] [ Designated as safety issue: No ]
    Beta cell function as measured during a frequently sampled IV glucose tolerance test

  • Insulin Sensitivity [ Time Frame: three weeks ] [ Designated as safety issue: No ]
    As assessed using IV glucose tolerance test and calculated using Min Mod units mU/mm


Enrollment: 27
Study Start Date: December 2006
Study Completion Date: May 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: tadalafil, ramapril, combo, placebo
placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, ramipril + tadalafil, washout, placebo+placebo for three weeks
Drug: Ramipril
Ramipril 10 mg per day for three weeks
Other Name: Altace
Drug: Tadalafil
tadalafil 10 mg every other day for three weeks
Other Name: Cialis
Drug: placebo
placebo matching ramipril
Other Name: matching ramipril
Drug: placebo
placebo matching tadalafil
Other Name: matching tadalfil
Active Comparator: 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
Drug: Ramipril
Ramipril 10 mg per day for three weeks
Other Name: Altace
Drug: Tadalafil
tadalafil 10 mg every other day for three weeks
Other Name: Cialis
Drug: placebo
placebo matching ramipril
Other Name: matching ramipril
Drug: placebo
placebo matching tadalafil
Other Name: matching tadalfil
Active Comparator: 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
Drug: Ramipril
Ramipril 10 mg per day for three weeks
Other Name: Altace
Drug: Tadalafil
tadalafil 10 mg every other day for three weeks
Other Name: Cialis
Drug: placebo
placebo matching ramipril
Other Name: matching ramipril
Drug: placebo
placebo matching tadalafil
Other Name: matching tadalfil
Active Comparator: 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
Drug: Ramipril
Ramipril 10 mg per day for three weeks
Other Name: Altace
Drug: Tadalafil
tadalafil 10 mg every other day for three weeks
Other Name: Cialis
Drug: placebo
placebo matching ramipril
Other Name: matching ramipril
Drug: placebo
placebo matching tadalafil
Other Name: matching tadalfil
Active Comparator: 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
Drug: Ramipril
Ramipril 10 mg per day for three weeks
Other Name: Altace
Drug: Tadalafil
tadalafil 10 mg every other day for three weeks
Other Name: Cialis
Drug: placebo
placebo matching ramipril
Other Name: matching ramipril
Drug: placebo
placebo matching tadalafil
Other Name: matching tadalfil
Active Comparator: 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
Drug: Ramipril
Ramipril 10 mg per day for three weeks
Other Name: Altace
Drug: Tadalafil
tadalafil 10 mg every other day for three weeks
Other Name: Cialis
Drug: placebo
placebo matching ramipril
Other Name: matching ramipril
Drug: placebo
placebo matching tadalafil
Other Name: matching tadalfil
Active Comparator: 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
Drug: Ramipril
Ramipril 10 mg per day for three weeks
Other Name: Altace
Drug: Tadalafil
tadalafil 10 mg every other day for three weeks
Other Name: Cialis
Drug: placebo
placebo matching ramipril
Other Name: matching ramipril
Drug: placebo
placebo matching tadalafil
Other Name: matching tadalfil
Active Comparator: 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
Drug: Ramipril
Ramipril 10 mg per day for three weeks
Other Name: Altace
Drug: Tadalafil
tadalafil 10 mg every other day for three weeks
Other Name: Cialis
Drug: placebo
placebo matching ramipril
Other Name: matching ramipril
Drug: placebo
placebo matching tadalafil
Other Name: matching tadalfil
Active Comparator: 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
Drug: Ramipril
Ramipril 10 mg per day for three weeks
Other Name: Altace
Drug: Tadalafil
tadalafil 10 mg every other day for three weeks
Other Name: Cialis
Drug: placebo
placebo matching ramipril
Other Name: matching ramipril
Drug: placebo
placebo matching tadalafil
Other Name: matching tadalfil
Active Comparator: 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
Drug: Ramipril
Ramipril 10 mg per day for three weeks
Other Name: Altace
Drug: Tadalafil
tadalafil 10 mg every other day for three weeks
Other Name: Cialis
Drug: placebo
placebo matching ramipril
Other Name: matching ramipril
Drug: placebo
placebo matching tadalafil
Other Name: matching tadalfil
Active Comparator: 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
Drug: Ramipril
Ramipril 10 mg per day for three weeks
Other Name: Altace
Drug: Tadalafil
tadalafil 10 mg every other day for three weeks
Other Name: Cialis
Drug: placebo
placebo matching ramipril
Other Name: matching ramipril
Drug: placebo
placebo matching tadalafil
Other Name: matching tadalfil
Active Comparator: 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
Drug: Ramipril
Ramipril 10 mg per day for three weeks
Other Name: Altace
Drug: Tadalafil
tadalafil 10 mg every other day for three weeks
Other Name: Cialis
Drug: placebo
placebo matching ramipril
Other Name: matching ramipril
Drug: placebo
placebo matching tadalafil
Other Name: matching tadalfil

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00750308

Sponsors and Collaborators
Vanderbilt University
National Institutes of Health (NIH)
Investigators
Principal Investigator: Nancy J Brown, M.D. Vanderbilt University
  More Information

Responsible Party: Nancy J. Brown, Professor of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00750308     History of Changes
Other Study ID Numbers: 060198 
Study First Received: September 5, 2008
Results First Received: January 6, 2010
Last Updated: December 8, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Tadalafil
Ramipril
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Antihypertensive Agents

ClinicalTrials.gov processed this record on July 28, 2016