Renin-Angiotensin Aldosterone System and Fibrinolysis Interaction in Humans-Specific Aim 3 - Full Text View

Sponsor:	Vanderbilt University
Collaborator:	National Institutes of Health (NIH)
Information provided by:	Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00685945

Purpose

The purpose of the study is to determine if giving isosorbide,a drug that is used to treat chest pain, affects blood vessel release of an anti-clotting factor.

Condition	Intervention
Obesity	Drug: Isosorbide Drug: Sildenafil

Study Type:	Interventional
Study Design:	Health Services Research, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment
Official Title:	Renin-Angiotensin Aldosterone System and Fibrinolysis(RAAS) Interaction in Humans- Specific Aim 3

Resource links provided by NLM:

MedlinePlus related topics: Obesity

Drug Information available for: Aldosterone Isosorbide-5-mononitrate omega-N-Methylarginine Isosorbide dinitrate Sildenafil Sildenafil citrate Isosorbide

U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

Measure tPA release [ Time Frame: end of each study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Measurement of forearm flow [ Time Frame: end of each study ] [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	April 2008
Estimated Study Completion Date:	April 2010
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Isosorbide- A: Active Comparator Subjects received Isosorbide Dinitrate 5 mg po after receiving Bradykinin and LNMMA. The Bradykinin and LNMMA is then repeated	Drug: Isosorbide Will use a non invasive measurement of endothelial function for first five minutes of the study. After arterial line and intravenous line placement; subject is given Aspirin 325 mg. After 30 minute rest period, a measurement of basal forearm bloodflow is obtained. After measurement, Bradykinin will be infused at 50, 100 and 200 ng/min. Each dose will be infused for 5 minutes and blood samples will be obtained. After a 30 minute rest period, LNMMA (12 umol/min) will be infused for 10 minutes and Bradykinin will be repeated. Blood samples will be obtained after each dose. Subjects will then be given IDSN 5 mg. One hour later, the LNMMA and Bradykinin infusion will be repeated and blood samples obtained.
Sildenafil - B: Active Comparator Subjects received Sildenafil after receiving Bradykinin and LNMMA. After 1 hour, Bradykinin and LNMMA is repeated.	Drug: Sildenafil Will use a non invasive measurement of endothelial function for first five minutes of the study.After arterial line and intravenous line placement; subject is given Aspirin 325 mg. After 30 minute rest period, a measurement of basal forearm bloodflow is obtained. After measurement, Bradykinin will be infused at 50, 100 and 200 ng/min. Each dose will be infused for 5 minutes and blood samples will be obtained. After a 30 minute rest period, LNMMA (12 umol/min) will be infused for 10 minutes and Bradykinin will be repeated. Blood samples will be obtained after each dose. Subjects will then be given Sildenafil 50 mg. One hour later, the LNMMA and Bradykinin infusion will be repeated and blood samples obtained.

Arms

Assigned Interventions

Isosorbide- A: Active Comparator

Subjects received Isosorbide Dinitrate 5 mg po after receiving Bradykinin and LNMMA. The Bradykinin and LNMMA is then repeated

Drug: Isosorbide

Will use a non invasive measurement of endothelial function for first five minutes of the study. After arterial line and intravenous line placement; subject is given Aspirin 325 mg. After 30 minute rest period, a measurement of basal forearm bloodflow is obtained. After measurement, Bradykinin will be infused at 50, 100 and 200 ng/min. Each dose will be infused for 5 minutes and blood samples will be obtained. After a 30 minute rest period, LNMMA (12 umol/min) will be infused for 10 minutes and Bradykinin will be repeated. Blood samples will be obtained after each dose. Subjects will then be given IDSN 5 mg. One hour later, the LNMMA and Bradykinin infusion will be repeated and blood samples obtained.

Sildenafil - B: Active Comparator

Subjects received Sildenafil after receiving Bradykinin and LNMMA. After 1 hour, Bradykinin and LNMMA is repeated.

Drug: Sildenafil

Will use a non invasive measurement of endothelial function for first five minutes of the study.After arterial line and intravenous line placement; subject is given Aspirin 325 mg. After 30 minute rest period, a measurement of basal forearm bloodflow is obtained. After measurement, Bradykinin will be infused at 50, 100 and 200 ng/min. Each dose will be infused for 5 minutes and blood samples will be obtained. After a 30 minute rest period, LNMMA (12 umol/min) will be infused for 10 minutes and Bradykinin will be repeated. Blood samples will be obtained after each dose. Subjects will then be given Sildenafil 50 mg. One hour later, the LNMMA and Bradykinin infusion will be repeated and blood samples obtained.

Detailed Description:

To test the hypothesis that the administration of the NO donor isosorbide dinitrate,but not the phosphodiesterase inhibitor sildenafil, will attenuate stimulated vascular t-PA release during ACE inhibition whereas both agents will improve glucose uptake.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

18-70 years of age
Male and female subjects
Surgical sterilization
Childbearing potential: beta HCg on study day
Subjects with a BMI of 25 or greater

Exclusion Criteria:

Diabetes type 1 to 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 mm Hg or taking hypertensives
Pregnancy/Breast Feeding
Cardiovascular disease such as myocardial infarction with 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable) deep vein thrombosis, pulmonary embolism, second or three 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
Diagnosis of asthma
Clinically significant gastrointestinal impairment that could interfere with drug absorption
Hematocrit <35%
Hyperlipidemic fasting Total Cholesterol >220
Impaired renal function (Serum creatinine >1.5 mg/dl)
History or presence of immunological or hematological disorders
Any underlying or acute disease requiring regular medication which could possible pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
Impaired hepatic function (SGOT, SGPT > 60)
Treatment with chronic systemic glucocorticoid therapy (more than 7 days in 1 month)
Treatment with lithium salts
History of Alcohol or drug abuse
Treatment with any investigational drug 1 month preceding study
Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
Inability to comply with the protocol

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00685945

Locations

United States, Tennessee
Vanderbilt University Medical Center-GCRC
Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

Vanderbilt University

National Institutes of Health (NIH)

Investigators

Principal Investigator:

Nancy J Brown, MD

Vanderbilt University

More Information

No publications provided

Responsible Party:	Vanderbilt University ( Nancy J. Brown, MD )
Study ID Numbers:	RAAS & Fibrinolysis, NIH grant # R060906
Study First Received:	May 27, 2008
Last Updated:	April 14, 2009
ClinicalTrials.gov Identifier:	NCT00685945 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Vanderbilt University:

Bradykinin
Obesity
Nitric Oxide Donor
tissue type plasminogen activator
isosorbide dinitrate

phosphodiesterase inhibitor
Renin-Angiotensin Aldosterone System
Fibrinolysis
Angiotensin converting enzyme

Additional relevant MeSH terms:

Isosorbide
Kininogens
Vasodilator Agents
Molecular Mechanisms of Pharmacological Action
Isosorbide-5-mononitrate
Hematologic Agents
Physiological Effects of Drugs
Diuretics
Tissue Plasminogen Activator
Isosorbide Dinitrate
Fibrinolytic Agents
Overweight
Nitric Oxide Donors
Body Weight
Signs and Symptoms

Fibrin Modulating Agents
Therapeutic Uses
Nutrition Disorders
Obesity
Bradykinin
Diuretics, Osmotic
Sildenafil
Enzyme Inhibitors
Cardiovascular Agents
Pharmacologic Actions
Protease Inhibitors
Phosphodiesterase Inhibitors
Natriuretic Agents
Cysteine Proteinase Inhibitors
Overnutrition

ClinicalTrials.gov processed this record on February 08, 2010