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

This study is currently recruiting participants.
Verified March 2013 by Zhejiang University
Sponsor:
Information provided by (Responsible Party):
Jiangtao Lai, Zhejiang University
ClinicalTrials.gov Identifier:
NCT01430780
First received: September 1, 2011
Last updated: March 21, 2013
Last verified: March 2013

September 1, 2011
March 21, 2013
August 2009
December 2013   (final data collection date for primary outcome measure)
flow-mediated dilation [ Time Frame: one year ] [ Designated as safety issue: Yes ]
Endothelial function evaluated by brachial artery ultrasound imaging during reactive hyperemia.
Same as current
Complete list of historical versions of study NCT01430780 on ClinicalTrials.gov Archive Site
  • serum superoxide dismutase (SOD) level [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    Superoxide dismutase (SOD) was determined by Xanthinoxidase method.
  • serum malondialdehyde (MDA) level [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    Malondialdehyde (MDA) was determined by thiobarbituric acid method.
  • serum hypersensitive C-reactive protein (hsCRP) level [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    An ELISA was used to determine hypersensitive C-reactive protein (hsCRP).
Same as current
Not Provided
Not Provided
 
A Prospective Study to Evaluate the Effect of Chronic Nitrate Therapy on Vasodilation Function in Coronary Heart Disease
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.

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.

Observational
Observational Model: Case Control
Time Perspective: Prospective
Not Provided
Not Provided
Non-Probability Sample

Patients with catheterization confirmed coronary artery disease.

Coronary Artery Disease
  • Drug: nitrate group
    Isosorbide Mononitrate orally 20mg twice per day.
  • Drug: control group
    placebo
  • control group
    placebo
    Intervention: Drug: control group
  • nitrate group
    Isosorbide Mononitrate orally 20mg twice per day.
    Intervention: Drug: nitrate group
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
68
December 2013
December 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years to 80 Years
No
Contact: Jiangtao Lai, Doctor +8657187236502 ericlaijt1@163.com
China
 
NCT01430780
2009A062
Yes
Jiangtao Lai, Zhejiang University
Zhejiang University
Not Provided
Principal Investigator: Jiangtao Lai, Doctor Zhejiang University
Zhejiang University
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP