A Prospective Study to Evaluate the Effect of Chronic Nitrate Therapy on Vasodilation Function in Coronary Heart Disease

March 21, 2013 updated by: Jiangtao Lai, Zhejiang University

A Prospective Study to Evaluate the Influence of Oxygen Free Radical Injury Induced by Long-term Nitrates Therapy on Vasodilation Function of Patients With Coronary Heart Disease

Basic studies has showed that sustained use of nitrates might associated with adverse effects on vascular function mediated by an increase in nitrate-induced oxidative stress. But it remains unclear whether oxidative stress increases with endothelial function impairment in patients with coronary artery disease (CAD) during administration of long-term oral nitrates. The investigators evaluated whether administration of long-term isosorbide mononitrate (ISMN) treatment was associated with oxidative stress increase and endothelial function impairment in patients with CAD.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Organic nitrates are widely prescribed for the treatment of angina pectoris in patients with coronary artery disease (CAD). In China, many patients with CAD are prescribed nitrates as a long-term treatment. The most commonly prescribed nitrates for long-time treatment is isosorbide mononitrate (ISMN). The reason for their use is that the majority of physicians believe chronic therapy with organic nitrates is associated with an improvement in symptoms and has neutral or potentially beneficial effects on long-term patient outcome, although this assumption remains unproven.

Recently, multiple lines of evidence documented that sustained use of nitrates was associated with adverse effects on vascular function which appeared to be mediated by an increase in nitrate-induced oxidative stress. The accumulation of oxygen free radicals during chronic nitrate therapy was associated with endothelial dysfunction, increased arterial sensitivity to vasoconstrictors and the development of abnormalities in a number of important enzymes involved in the regulation of vascular homeostasis, including the superoxide dismutase, protein kinase C, matrix metalloproteinases, and prostaglandin synthase. This may lead to development of nitrate tolerance, endothelial dysfunction. Furthermore, endothelial dysfunction is a risk factor for worse prognosis of patients with CAD.

Up to date, some clinical research focus on how to prevent tolerance and clinical outcome of nitrate therapy were involved short follow-up periods of only a few weeks. It is too short to assess the true clinical impact of nitrate-induced endothelial dysfunction, and the safety of long-term nitrate therapy requires systematic review. So prospective, randomized study with longer treatment period is needed to observe the chronic impact of nitrate therapy on endothelial function.

Therefore, the investigators prospectively investigated whether long-term ISMN therapy had any influence on endothelial function evaluated by brachial artery ultrasound imaging during reactive hyperemia in patients with catheterization confirmed CAD, and whether this was associated with increased oxidization or inflammation burden.

Study Type

Observational

Enrollment (Anticipated)

68

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310003
        • Recruiting
        • Department of Cardiology, First Affiliated Hospital, College of Medicine, Zhejiang University
        • Contact:
          • Jiangtao Lai, Doctor
        • Sub-Investigator:
          • Yunpeng Shang, Doctor

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

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with catheterization confirmed coronary artery disease.

Description

Inclusion Criteria:

  • Individuals were considered eligible for enrollment if they had at least 1 significant de novo stenosis (reduction ≥50% of the lumen diameter) on any coronary vessel at angiography.

Exclusion Criteria:

  • Patients with liver and renal failure with creatinine>3 mg/dL were excluded.

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
control group
placebo
Drug: control group
placebo
nitrate group
Isosorbide Mononitrate orally 20mg twice per day.
Drug: nitrate group
Isosorbide Mononitrate orally 20mg twice per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
flow-mediated dilation
Time Frame: one year
Endothelial function evaluated by brachial artery ultrasound imaging during reactive hyperemia.
one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
serum superoxide dismutase (SOD) level
Time Frame: one year
Superoxide dismutase (SOD) was determined by Xanthinoxidase method.
one year
serum malondialdehyde (MDA) level
Time Frame: one year
Malondialdehyde (MDA) was determined by thiobarbituric acid method.
one year
serum hypersensitive C-reactive protein (hsCRP) level
Time Frame: one year
An ELISA was used to determine hypersensitive C-reactive protein (hsCRP).
one year

Collaborators and Investigators

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

Sponsor

Zhejiang University

Investigators

  • Principal Investigator: Jiangtao Lai, Doctor, Zhejiang University

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

August 1, 2009

Primary Completion (Anticipated)

December 1, 2013

Study Completion (Anticipated)

December 1, 2013

Study Registration Dates

First Submitted

September 1, 2011

First Submitted That Met QC Criteria

September 6, 2011

First Posted (Estimate)

September 8, 2011

Study Record Updates

Last Update Posted (Estimate)

March 22, 2013

Last Update Submitted That Met QC Criteria

March 21, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2009A062

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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