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

This study is currently recruiting participants. (see Contacts and Locations)
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
  Purpose

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.


Condition Intervention
Coronary Artery Disease
Drug: nitrate group
Drug: control group

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
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

Resource links provided by NLM:


Further study details as provided by Zhejiang University:

Primary Outcome Measures:
  • flow-mediated dilation [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    Endothelial function evaluated by brachial artery ultrasound imaging during reactive hyperemia.


Secondary Outcome Measures:
  • 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).


Estimated Enrollment: 68
Study Start Date: August 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with catheterization confirmed coronary artery disease.

Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01430780

Contacts
Contact: Jiangtao Lai, Doctor +8657187236502 ericlaijt1@163.com

Locations
China, Zhejiang
Department of Cardiology, First Affiliated Hospital, College of Medicine, Zhejiang University Recruiting
Hangzhou, Zhejiang, China, 310003
Contact: Jiangtao Lai, Doctor         
Sub-Investigator: Yunpeng Shang, Doctor         
Sponsors and Collaborators
Zhejiang University
Investigators
Principal Investigator: Jiangtao Lai, Doctor Zhejiang University
  More Information

No publications provided by Zhejiang University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jiangtao Lai, MD, Zhejiang University
ClinicalTrials.gov Identifier: NCT01430780     History of Changes
Other Study ID Numbers: 2009A062
Study First Received: September 1, 2011
Last Updated: March 21, 2013
Health Authority: China: Ministry of Science and Technology

Keywords provided by Zhejiang University:
Coronary artery disease
nitrate
endothelium

Additional relevant MeSH terms:
Heart Diseases
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on September 22, 2014