ACE Inhibition and Novel Cardiovascular Risk Factors

This study has been completed.
Sponsor:
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00051389
First received: January 9, 2003
Last updated: January 18, 2008
Last verified: January 2008
  Purpose

To determine the effects of an angiotensin converting enzyme inhibitor (ACE inhibitor), fosinopril, on multiple blood markers in 286 adults at high risk for cardiovascular disease.


Condition Intervention Phase
Cardiovascular Diseases
Heart Diseases
Hypertension
Drug: Fosinopril
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Prevention

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Study Start Date: February 2002
Study Completion Date: January 2007
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Detailed Description:

BACKGROUND:

Angiotensin converting enzyme inhibitors (ACE inhibitors) may prevent cardiovascular events in high risk persons and improve skeletal muscle function in heart failure patients by means of mechanisms that are independent of blood pressure changes. However, there is limited knowledge of all the mechanisms underlying the therapeutic benefits of ACE inhibition. ACE inhibitors may favorably modify markers of fibrinolysis, inflammation, endothelial function, and extracellular tissue remodeling, all of which are associated with atherosclerosis and cardiovascular disease. But, clinical trial evidence on these effects is limited. In addition, polymorphisms of the ACE, angiotensinogen, PAI-1 and IL-6 genes may modify the therapeutic response to ACE inhibitors.

DESIGN NARRATIVE:

This was a double-blind cross-over, randomized, placebo controlled trial in 286 persons with high cardiovascular risk to compare the effects of 6 months of treatment with fosinopril and 6 months with placebo on the following primary outcomes: plasma plasminogen activator inhibitor-1 (PAI-1) antigen, C- reactive protein (CRP), interleukin-6 (IL-6) and soluble vascular cell adhesion molecule-1 (sVCAM-1). The secondary objectives were (a) to assess the effects of fosinopril on IL-6/IL-6 Soluble Receptor ratio, PAI-1 activity, tissue plasminogen activator (TPA) antigen, fibrinogen, endothelin-1, TNF-alpha, soluble intercellular cell adhesion molecule-1 (sICAM-1), E-selectin, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1); and (b) to explore the effects of ACE, angiotensinogen, PAI-1, and IL-6 gene polymorphisms on these biomarkers, and test the interaction of the gene polymorphisms with the effects of fosinopril. The study had sufficient power to detect small changes in several biomarkers compared to placebo. The assessment of these biological mechanisms had clinical relevance for identifying the patients who may benefit the most from ACE inhibition. While the focus of the study was on novel cardiovascular risk factors, the results may also have future implications for developing new indications for ACE inhibitors, such as, for example, the prevention of age-related muscle wasting and physical disabilities in older persons, for which inflammation may be a causal factor.

  Eligibility

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

No eligibility criteria

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00051389

Sponsors and Collaborators
Investigators
Investigator: Marco Pahor Wake Forest School of Medicine
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00051389     History of Changes
Other Study ID Numbers: 155
Study First Received: January 9, 2003
Last Updated: January 18, 2008
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Cardiovascular Diseases
Heart Diseases
Hypertension
Vascular Diseases
Fosinopril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014