To determine the effects of an angiotensin converting enzyme inhibitor (ACE inhibitor), enalapril, on multiple blood markers in 290 adults at high risk for cardiovascular disease.

Condition	Treatment or Intervention	Phase
Cardiovascular Diseases Heart Diseases Hypertension	Drug: Enalapril	Phase III

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 is a double-blind cross-over, randomized, placebo controlled trial in 290 persons with high cardiovascular risk to compare the effects of 6 months of treatment with enalapril 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 are (a) to assess the effects of enalapril 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 enalapril. The study will have sufficient power to detect small changes in several biomarkers compared to placebo. The assessment of these biological mechanisms will have clinical relevance for identifying the patients who may benefit the most from ACE inhibition. While the focus of the study is 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.

Ages Eligible for Study:  55 Years and above,  Genders Eligible for Study:  Both

Criteria

No eligibility criteria

North Carolina
      Wake Forest University Health Sciences, Winston Salem,  North Carolina,  27157,  United States; Recruiting

Study chairs or principal investigators

Marco Pahor,  Wake Forest University   

Study ID Numbers:  155
Record last reviewed:  August 2004
Record first received:  January 9, 2003
ClinicalTrials.gov Identifier:  NCT00051389
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27