Defining Strategies for Improving Endothelial and Fibrinolytic Dysfunction in Obesity

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2009 by Vanderbilt University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00608465
First received: January 22, 2008
Last updated: April 10, 2009
Last verified: April 2009
  Purpose

The combination of high blood pressure and having central obesity is an increasing important factor for heart disease in men and women. It can also lead to the early development of hardening of the arteries and increased risk of a stroke. This study will analyze patients' genetic make up to identify who may be at greater risk for heart disease and strokes in relationship to high blood pressure and central obesity.


Condition Intervention Phase
Metabolic Syndrome X
Drug: Eplerenone
Drug: Ramipril
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Defining Strategies for Improving Endothelial and Fibrinolytic Dysfunction in Obesity

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Secreted factors from adipocytes have autocrine, paracrine and endocrine effects that have a deleterious effect on the fibrinolytic system, either by enhancing PAI-1 production or impairing endothelial t-PA release [ Time Frame: 10-Week period ] [ Designated as safety issue: No ]
  • This study will analyze patients' genetic make up to identify who may be at greater risk for heart disease and strokes in relationship to high blood pressure and central obesity. [ Time Frame: 10-weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: May 2006
Estimated Study Completion Date: May 2011
Estimated Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Treatment A
Eplerenone (study drug)
Drug: Eplerenone
5 mg x 1 week followed by 10 mg x 9 weeks.
Other Name: Inspra
Active Comparator: Treatment B
Ramipril
Drug: Ramipril
Ramipril 5mg qd x 1 week f/b Ramipril qd x 9 weeks.

Detailed Description:

Obesity is an increasingly important risk factor for cardiovascular disease in men and women and is associated with the premature development of atherosclerosis, and increased risk of stroke. A classical perspective of cardiovascular risk does not adequately explain all of the cardiovascular events associated with obesity. Elevated plasma levels of plasminogen activator inhibitor type I (PAI-1) are one of the biochemical hallmarks for obesity and likely contribute the increased risk of atherothrombotic events in patients with obesity. The central hypothesis of this proposal is that the increased risk of atherothrombotic events in patients with obesity. The central hypothesis of this proposal is that vascular PAI-1 excess promotes the development of intravascular thrombosis. We will test the hypothesis that secreted factors from adipocytes have autocrine, paracrine and endocrine effects that have a deleterious effect on the fibrinolytic system, either by enhancing PAI-1 production or impairing endothelial t-PA release. From a public health perspective, there is no greater threat to America's cardiovascular health than the epidemic of obesity. It is anticipated that this study will provide new insights nto the molecular mechanisms that contribute to the development of fibrinolytic dysfunction and cardiovascular disease in obesity.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or females between the ages of 18 to 65 years of age.
  • Documented diagnosis for the metabolic syndrome:
  • Subjects with hypertension (SP>130mmHg)
  • Subjects with central obesity (females waist >35"; males waist >40")
  • Subjects with dyslipidemia (HDL <40mg/dl, triglycerides > 150 mg/dl)
  • Subjects who are insulin resistance (fasting glucose >100mg/dl)

Exclusion Criteria:

  • Subjects who smoke
  • Women who are pregnant (confirmed by urine beta-HCG).
  • Women who are breast feeding
  • Subjects with documentation of the following health risk:

    • Subjects with serum creatinine >2.0 mg/dl (males), >1.8 mg/dl (females)
    • Subjects whose creatinine clearance < 50 mls/min
    • Subjects with serum potassium >5.5mEql
    • Subjects with Type 2 diabetes with microalbuminuria (spot urine protein/creatinine ration >0.2)
  • Subjects who are currently taking the following medications:
  • Warfarin
  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: NCT00608465

Contacts
Contact: James AS Muldowney, III, MD 615-936-1719 james.muldowney@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: James AS Muldowney, III, MD    615-936-1750    james.muldowney@vanderbilt.edu   
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: James AS Muldowney, MD Vanderbilt University
  More Information

No publications provided

Responsible Party: James A.S. Muldowney III, MD, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT00608465     History of Changes
Other Study ID Numbers: 060369, 060369
Study First Received: January 22, 2008
Last Updated: April 10, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt University:
Fibrolytic Dysfunction
Obesity
PAI-1

Additional relevant MeSH terms:
Metabolic Syndrome X
Obesity
Body Weight
Glucose Metabolism Disorders
Hyperinsulinism
Insulin Resistance
Metabolic Diseases
Nutrition Disorders
Overnutrition
Overweight
Signs and Symptoms
Eplerenone
Ramipril
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Cardiovascular Agents
Diuretics
Diuretics, Potassium Sparing
Enzyme Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Mineralocorticoid Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014