Coronary Artery DiseaseNCT01430780
A Prospective Study to Evaluate the Effect of Chronic Nitrate Therapy on Vasodilation Function in Coronary Heart Disease
An observational study of Coronary Artery Disease, run by Zhejiang University at 1 site in China.
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)… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- nitrate group
- Type of treatment
- Pill or oral medicine
- How many people
- 68 participants
- Where
- 1 siteChina
- Study dates
- Aug 2009to Dec 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with catheterization confirmed coronary artery disease.
Who may be able to join
- 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.
Who cannot join
- Patients with liver and renal failure with creatinine>3 mg/dL were excluded.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Cardiology, First Affiliated Hospital, College of Medicine, Zhejiang University
Hangzhou, Zhejiang, 310003
Jiangtao Lai, Doctor
Yunpeng Shang, Doctor
About this study
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
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.
Read the 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.
- Conditions
- Coronary Artery Disease
- Being tested
- nitrate group, control group
- Keywords
- Coronary artery disease, nitrate, endothelium
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nitrate groupDrug
Isosorbide Mononitrate orally 20mg twice per day.
control groupDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| control group | placebo Receives: Drug: control group | |
| nitrate group | Isosorbide Mononitrate orally 20mg twice per day. Receives: Drug: nitrate group |
What is being measured
The primary outcome is the main question the study is designed to answer.
flow-mediated dilation
Endothelial function evaluated by brachial artery ultrasound imaging during reactive hyperemia.
Measured: one year
Secondary outcomes (3)
serum superoxide dismutase (SOD) level
Superoxide dismutase (SOD) was determined by Xanthinoxidase method.
Measured: one year
serum malondialdehyde (MDA) level
Malondialdehyde (MDA) was determined by thiobarbituric acid method.
Measured: one year
serum hypersensitive C-reactive protein (hsCRP) level
An ELISA was used to determine hypersensitive C-reactive protein (hsCRP).
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2011 (estimated)
- Study startAug 2009
- Primary completionDec 2013 (estimated)
- Study completionDec 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jiangtao Lai, Zhejiang University
- Investigators
- Jiangtao Lai, Doctor, Principal investigator, Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01430780
- Sponsor's protocol ID
- 2009A062
- Status last verified
- Mar 2013
- First submitted
- 1 Sep 2011
- Last updated
- 22 Mar 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lai J, Wu B, Sun J, Shang Y, Zhu J. Long-term isosorbide mononitrate treatment impairs endothelial function in patients with coronary artery disease. Coron Artery Dis. 2013 Nov;24(7):566-71. doi: 10.1097/MCA.0000000000000029.
PubMed 23994882
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01430780
- Acronym / sponsor ID
- 2009A062
- Conditions
- Coronary Artery Disease
- Keywords
- Coronary artery disease, nitrate, endothelium
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- Zhejiang UniversityUniversity, hospital or other
- Study start
- Aug 2009
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2013 (estimated)
- First posted
- 8 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| control group | – | Drug: control groupplacebo |
| nitrate group | – | Drug: nitrate groupIsosorbide Mononitrate orally 20mg twice per day. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with catheterization confirmed coronary artery disease.
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- Patients with liver and renal failure with creatinine>3 mg/dL were excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nitrate groupIsosorbide Mononitrate orally 20mg twice per day. | Drug | nitrate group |
| control groupplacebo | Drug | control group |
Primary outcome
flow-mediated dilation
Time frame: one year
Endothelial function evaluated by brachial artery ultrasound imaging during reactive hyperemia.
3 secondary outcomes
serum superoxide dismutase (SOD) level
Time frame: one year
serum malondialdehyde (MDA) level
Time frame: one year
serum hypersensitive C-reactive protein (hsCRP) level
Time frame: one year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2013.
- Derived from this study: PubMed 23994882Lai J, Wu B, Sun J, Shang Y, Zhu J. Long-term isosorbide mononitrate treatment impairs endothelial function in patients with coronary artery disease. Coron Artery Dis. 2013 Nov;24(7):566-71. doi: 10.1097/MCA.0000000000000029.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jiangtao Lai, Doctor principal investigator
Zhejiang University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Coronary Artery Disease, run by Zhejiang University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jiangtao Lai, Doctor (+8657187236502, ericlaijt1@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
flow-mediated dilation (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01430780, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2013.