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Defining Strategies for Improving Endothelial and Fibrinolytic Dysfunction in Obesity

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ClinicalTrials.gov Identifier: NCT00608465
Recruitment Status : Terminated (Lack of enrollment)
First Posted : February 6, 2008
Results First Posted : May 1, 2017
Last Update Posted : August 11, 2017
Sponsor:
Information provided by (Responsible Party):
James Muldowney, Vanderbilt University

Brief Summary:
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 or disease Intervention/treatment Phase
Metabolic Syndrome X Drug: Eplerenone Drug: Ramipril Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Defining Strategies for Improving Endothelial and Fibrinolytic Dysfunction in Obesity
Actual Study Start Date : May 2006
Actual Primary Completion Date : May 2009
Actual Study Completion Date : May 2011

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00608465


Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: James AS Muldowney, MD Vanderbilt University Medical Center

Responsible Party: James Muldowney, Assistant Professor of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00608465     History of Changes
Other Study ID Numbers: 060369
060369
First Posted: February 6, 2008    Key Record Dates
Results First Posted: May 1, 2017
Last Update Posted: August 11, 2017
Last Verified: July 2017

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

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