ACE Inhibition and Novel Cardiovascular Risk Factors

February 17, 2016 updated by: National Heart, Lung, and Blood Institute (NHLBI)
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

No eligibility criteria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Marco Pahor, Wake Forest University Health Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2002

Primary Completion (Actual)

January 1, 2007

Study Completion (Actual)

January 1, 2007

Study Registration Dates

First Submitted

January 9, 2003

First Submitted That Met QC Criteria

January 10, 2003

First Posted (Estimate)

January 13, 2003

Study Record Updates

Last Update Posted (Estimate)

February 18, 2016

Last Update Submitted That Met QC Criteria

February 17, 2016

Last Verified

January 1, 2008

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 155
  • R01HL068901 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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