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

Coronary Artery Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01430780
• Other study ID #: 2009A062
• Status: Recruiting
• Phase: N/A
• First received: September 1, 2011
• Last updated: March 21, 2013
• Start date: August 2009
• Est. completion date: December 2013

Study information

• Verified date: March 2013
• Source: Zhejiang University
• Contact: Jiangtao Lai, Doctor
• Phone: +8657187236502
• Email: ericlaijt1[@]163.com
• Is FDA regulated: No
• Health authority: China: Ministry of Science and Technology
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Heart Diseases
• Myocardial Ischemia

Intervention

Drug:
• nitrate group
Isosorbide Mononitrate orally 20mg twice per day.
• control group
placebo

Locations

Country	Name	City	State
China	Department of Cardiology, First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	flow-mediated dilation	Endothelial function evaluated by brachial artery ultrasound imaging during reactive hyperemia.	one year	Yes
Secondary	serum superoxide dismutase (SOD) level	Superoxide dismutase (SOD) was determined by Xanthinoxidase method.	one year	Yes
Secondary	serum malondialdehyde (MDA) level	Malondialdehyde (MDA) was determined by thiobarbituric acid method.	one year	Yes
Secondary	serum hypersensitive C-reactive protein (hsCRP) level	An ELISA was used to determine hypersensitive C-reactive protein (hsCRP).	one year	Yes