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

NCT00750308 | Completed Results

• 1 other identifier: 060198
• Study Type: interventional
• Target: 27
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Metabolic Syndrome

Outcome Measures

Primary Outcomes (2)

• Beta Cell Function

  Beta cell function as measured during a frequently sampled IV glucose tolerance test

  3 hours

• Insulin Sensitivity

  As assessed using IV glucose tolerance test and calculated using Min Mod units mU/mm

  three weeks

Study Arms (12)

tadalafil, ramapril, combo, placebo

ACTIVE COMPARATOR

placebo+tadalafil for three weeks, washout, placebo+ramipril for three weeks, washout, ramipril + tadalafil, washout, placebo+placebo for three weeks

Drug: Ramipril; Drug: Tadalafil; Drug: placebo

ramipril, tadalafil, placebo, combo

ACTIVE COMPARATOR

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; Drug: Tadalafil; Drug: placebo

combo, placebo, tadalafil, ramipril

ACTIVE COMPARATOR

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; Drug: Tadalafil; Drug: placebo

placebo, combo, ramipril, tadalafil

ACTIVE COMPARATOR

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; Drug: Tadalafil; Drug: placebo

tadalafil, placebo, ramipril, combo

ACTIVE COMPARATOR

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; Drug: Tadalafil; Drug: placebo

ramipril, combo, tadalfil, placebo

ACTIVE COMPARATOR

placebo+ramipril for three weeks, washout, ramipril+tadalafil for three weeks, washout, placebo+tadalafil for three weeks, washout, placebo for three weeks

Drug: Ramipril; Drug: Tadalafil; Drug: placebo

combo, ramipril, placebo, tadalafil

ACTIVE COMPARATOR

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; Drug: Tadalafil; Drug: placebo

placebo, tadalafil, combo, ramipril

ACTIVE COMPARATOR

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; Drug: Tadalafil; Drug: placebo

tadalafil, combo, placebo, ramipril

ACTIVE COMPARATOR

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; Drug: Tadalafil; Drug: placebo

ramipril, placebo, combo, tadalafil

ACTIVE COMPARATOR

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; Drug: Tadalafil; Drug: placebo

combo, tadalafil, ramipril, placebo

ACTIVE COMPARATOR

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; Drug: Tadalafil; Drug: placebo

placebo, ramipril, tadalafil, combo

ACTIVE COMPARATOR

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; Drug: Tadalafil; Drug: placebo

Interventions

Ramipril DRUG

Ramipril 10 mg per day for three weeks

Also known as: Altace

combo, placebo, tadalafil, ramipril; combo, ramipril, placebo, tadalafil; combo, tadalafil, ramipril, placebo; placebo, combo, ramipril, tadalafil; placebo, ramipril, tadalafil, combo; placebo, tadalafil, combo, ramipril; ramipril, combo, tadalfil, placebo; ramipril, placebo, combo, tadalafil; ramipril, tadalafil, placebo, combo; tadalafil, combo, placebo, ramipril; tadalafil, placebo, ramipril, combo; tadalafil, ramapril, combo, placebo

Tadalafil DRUG

tadalafil 10 mg every other day for three weeks

Also known as: Cialis

combo, placebo, tadalafil, ramipril; combo, ramipril, placebo, tadalafil; combo, tadalafil, ramipril, placebo; placebo, combo, ramipril, tadalafil; placebo, ramipril, tadalafil, combo; placebo, tadalafil, combo, ramipril; ramipril, combo, tadalfil, placebo; ramipril, placebo, combo, tadalafil; ramipril, tadalafil, placebo, combo; tadalafil, combo, placebo, ramipril; tadalafil, placebo, ramipril, combo; tadalafil, ramapril, combo, placebo

placebo DRUG

placebo matching ramipril

Also known as: matching ramipril

combo, placebo, tadalafil, ramipril; combo, ramipril, placebo, tadalafil; combo, tadalafil, ramipril, placebo; placebo, combo, ramipril, tadalafil; placebo, ramipril, tadalafil, combo; placebo, tadalafil, combo, ramipril; ramipril, combo, tadalfil, placebo; ramipril, placebo, combo, tadalafil; ramipril, tadalafil, placebo, combo; tadalafil, combo, placebo, ramipril; tadalafil, placebo, ramipril, combo; tadalafil, ramapril, combo, placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Vanderbilt University: lead
• National Institutes of Health (NIH): collaborator

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

Ramipril; Tadalafil

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Indole Alkaloids; Indoles; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Dr. Nancy J. Brown
• Organization: Vanderbilt University

nancy.j.brown@vanderbilt.edu

615-343-8701

Study Officials

• Nancy J Brown, M.D.

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 5, 2008
• First Posted: September 10, 2008
• Study Start: December 1, 2006
• Primary Completion: January 1, 2009
• Study Completion: May 1, 2009
• Last Updated: December 18, 2014
• Results First Posted: April 12, 2010

Record last verified: 2014-12