Coronary Artery DiseaseNCT00109018
Biomarkers for Cardiovascular Disease
An observational study of Coronary Artery Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Biomarkers for Cardiovascular Disease Summary: This study will examine the function of the lining cells of blood vessels and measure substances in the blood to see how they relate to various blood tests, including new tests under development to determine cardiovascular disease risk. Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Coronary Artery Disease
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Apr 2005to 15 Apr 2009
- 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 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adults older than 21, of both sexes:
- The initial study group will consist of 120 subjects, which will consist of 100 subjects with documented CAD (by cardiac catheterization showing greater than or equal to 70% stenosis in an epicardial vessel), previously documented MI (based on ECG or cardiac enzymes) or CAD risk equivalents (diabetes, peripheral vascular disease, abdominal aortic aneurysm, symptomatic carotid disease, or multiple risk factors that confer a 10 year risk of greater than 20% as defined by the Framingham Risk Score) and 20 healthy age- and sex-matched controls.
- Written informed consent.
Who cannot join
- Atrial fibrillation
- Any contraindications to oral nitrates
- Hypotension, bradycardia.
- Myocardial infarction within the prior 30 days
- Symptoms of acute CHF
- Pregnant women
Show all 9Show fewer
- Receiving active treatment for cancer
- Any other condition that may interfere with the interpretation of the study results or not be in the best interest of the subject in the opinion of the investigator.
- Since oral nitrate therapy is known to affect serum and possibly whole blood nitrite levels, we will exclude patients on long-acting nitrates for the initial group of 100 cardiac patients. Those patients on chronic nitrate therapy will subsequently be included in the later portion of the study but will be analyzed separately.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Nitrite as a Marker of Cardiovascular Risk; Development of Novel Biomarkers in Patients With Coronary Artery Disease
Biomarkers for Cardiovascular Disease
Summary: This study will examine the function of the lining cells of blood vessels and measure substances in the blood to see how they relate to various blood tests, including new tests under development to determine cardiovascular disease risk. Nitric oxide is a molecule produced by healthy blood vessels that helps keep them relaxed. Nitrate is a substance formed from nitric oxide in the blood. The release of nitric oxide by blood vessels is reduced in patients with coronary artery disease, compared with healthy people. Also, blood nitrite levels rise in some of these patients. Other substances in the blood and urine also change with risk for heart disease. This study will measure nitrite levels and other inflammatory substances in the blood and urine.
Read more
Healthy volunteers, people with various risk factors for heart disease, and people with blockage of one or more major heart arteries or a history of heart attack may be eligible for this study. Candidates must be 21 years of age or older. People who have an irregular heart rhythm or who cannot take oral nitrates are excluded.
Participants undergo the following tests and procedures:
- Blood tests: Samples are drawn three times for routine tests and to look for certain proteins that may affect the heart. Samples are collected once before any other tests, once before starting the exercise stress test (see below) and again after the stress test.
- Urine test: A sample may be tested for proteins in the urine and for other research studies.
- Brachial artery reactivity study: This ultrasound study tests how well a person's arteries widen. The subject rests on a bed. An ultrasound measuring device is placed over the artery just above the elbow. The size of the artery and blood flow through it are measured before and after inflating a pressure cuff around the forearm. The pressure cuff stops the flow of blood to the arm for 5 minutes and then is released while more ultrasound pictures are taken. After the subject rests, a nitroglycerin tablet (medicine that causes blood vessels to relax) is placed under the tongue. After the nitroglycerin is given, the size of the artery and blood flow through it are measured again. After a rest period, the study will be repeated in the healthy volunteers and first 20 patients with heart disease.
- Echocardiography (heart ultrasound): This test involves holding a small probe against the chest to use sound waves for obtaining pictures of the heart. A small catheter (plastic tube) may be placed in a vein to inject a contrast agent that enhances the pictures.
- Metabolic stress testing: Subjects will be asked to breathe in and out of a mask while baseline measurements are taken. Then they exercise on a treadmill while wearing a breathing mask. This test shows how much oxygen the body uses at rest and with exercise.
- Genetic testing (optional): A blood sample is collected to examine DNA - genetic material that determines inherited traits and contains information about body proteins. Some parts of DNA may be used as markers of the level of damage produced by oxygen by-products that may reflect the extent of heart disease in patients. Also, gene variations may make an individual more likely to develop a heart problem. Such markers may guide doctors in predicting how fast the disease will progress or may help find a new type of drug to prevent disease.
- Time requirements: This study is expected to take approximately 5-6 hours for completion within one or two days.
- Follow-up: Patients are contacted by phone every 6 months for information on chest pain, surgical procedures related to the heart, and hospitalizations.
Read the detailed description
Cardiovascular events are a major cause of morbidity and mortality world-wide and traditional risk factor assessment is limited in its ability to predict which patients will have an event. The endothelium is known to play a central role in vascular homeostasis and nitric oxide (NO) is believed to be the main component responsible for normal endothelial function. Increasing evidence suggests that oxidative stress leading to reduced NO bioavailability and subsequent endothelial dysfunction is an important factor in the progression of vascular diseases. Further investigation of NO metabolites in blood may provide insight into the mechanisms of endothelial dysfunction and disease progression. Preliminary data suggest that although plasma nitrite levels are decreased in CAD patients and correlate with endothelial dysfunction, the nitrite within red blood cells and whole blood is compensatorily increased. Since this new measure is more reproducible and convenient to measure, it may serve as a biomarker of endothelial dysfunction. A prospective study of nitrite and other novel NO-based assays, proteomics, and current biomarkers linked to endothelial function phenotype will allow further investigation into the pathophysiology of endothelial dysfunction and permit development of future markers of atherothrombosis.
- Conditions
- Coronary Artery Disease
- Keywords
- Risk Assessment, Coronary Heart Disease, Vascular Function, Nitric Oxide Metabolites, Blood Tests, Nitrite, Flow-Mediated Dilation, Biomarker, Endothelial Dysfunction, Coronary Artery Disease, CAD, Coronary Artery Disease At Risk, Healthy Volunteer
- Medical subject headings
- Coronary Artery Disease, Coronary Disease
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2005 (estimated)
- Study start19 Apr 2005
- Study completion15 Apr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- 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
- Enrolment
- 120 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00109018
- Sponsor's protocol ID
- 050145
- Other IDs
- 05-H-0145
- Status last verified
- 15 Apr 2009
- First submitted
- 21 Apr 2005
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Myerburg RJ, Interian A Jr, Mitrani RM, Kessler KM, Castellanos A. Frequency of sudden cardiac death and profiles of risk. Am J Cardiol. 1997 Sep 11;80(5B):10F-19F. doi: 10.1016/s0002-9149(97)00477-3.
PubMed 9291445Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998 May 12;97(18):1837-47. doi: 10.1161/01.cir.97.18.1837.
PubMed 9603539Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002 Nov 14;347(20):1557-65. doi: 10.1056/NEJMoa021993.
PubMed 12432042
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nitrite as a Marker of Cardiovascular Risk; Development of Novel Biomarkers in Patients With Coronary Artery Disease
- ClinicalTrials.gov ID
- NCT00109018
- Acronym / sponsor ID
- 050145
- Conditions
- Coronary Artery Disease
- Keywords
- Risk Assessment, Coronary Heart Disease, Vascular Function, Nitric Oxide Metabolites, Blood Tests, Nitrite, Flow-Mediated Dilation, Biomarker
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 120 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 19 Apr 2005
- Study completion
- 15 Apr 2009
- First posted
- 22 Apr 2005 (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.
Biomarkers for Cardiovascular Disease
Summary: This study will examine the function of the lining cells of blood vessels and measure substances in the blood to see how they relate to various blood tests, including new tests under development to determine cardiovascular disease risk. Nitric oxide is a molecule produced by healthy blood vessels that helps keep them relaxed. Nitrate is a substance formed from nitric oxide in the blood. The release of nitric oxide by blood vessels is reduced in patients with coronary artery disease, compared with healthy people. Also, blood nitrite levels rise in some of these patients. Other substances in the blood and urine also change with risk for heart disease. This study will measure nitrite levels and other inflammatory substances in the blood and urine.
Healthy volunteers, people with various risk factors for heart disease, and people with blockage of one or more major heart arteries or a history of heart attack may be eligible for this study. Candidates must be 21 years of age or older. People who have an irregular heart rhythm or who cannot take oral nitrates are excluded.
Participants undergo the following tests and procedures:
- Blood tests: Samples are drawn three times for routine tests and to look for certain proteins that may affect the heart. Samples are collected once before any other tests, once before starting the exercise stress test (see below) and again after the stress test.
- Urine test: A sample may be tested for proteins in the urine and for other research studies.
- Brachial artery reactivity study: This ultrasound study tests how well a person's arteries widen. The subject rests on a bed. An ultrasound measuring device is placed over the artery just above the elbow. The size of the artery and blood flow through it are measured before and after inflating a pressure cuff around the forearm. The pressure cuff stops the flow of blood to the arm for 5 minutes and then is released while more ultrasound pictures are taken. After the subject rests, a nitroglycerin tablet (medicine that causes blood vessels to relax) is placed under the tongue. After the nitroglycerin is given, the size of the artery and blood flow through it are measured again. After a rest period, the study will be repeated in the healthy volunteers and first 20 patients with heart disease.
- Echocardiography (heart ultrasound): This test involves holding a small probe against the chest to use sound waves for obtaining pictures of the heart. A small catheter (plastic tube) may be placed in a vein to inject a contrast agent that enhances the pictures.
- Metabolic stress testing: Subjects will be asked to breathe in and out of a mask while baseline measurements are taken. Then they exercise on a treadmill while wearing a breathing mask. This test shows how much oxygen the body uses at rest and with exercise.
- Genetic testing (optional): A blood sample is collected to examine DNA - genetic material that determines inherited traits and contains information about body proteins. Some parts of DNA may be used as markers of the level of damage produced by oxygen by-products that may reflect the extent of heart disease in patients. Also, gene variations may make an individual more likely to develop a heart problem. Such markers may guide doctors in predicting how fast the disease will progress or may help find a new type of drug to prevent disease.
- Time requirements: This study is expected to take approximately 5-6 hours for completion within one or two days.
- Follow-up: Patients are contacted by phone every 6 months for information on chest pain, surgical procedures related to the heart, and hospitalizations.
Detailed description
Cardiovascular events are a major cause of morbidity and mortality world-wide and traditional risk factor assessment is limited in its ability to predict which patients will have an event. The endothelium is known to play a central role in vascular homeostasis and nitric oxide (NO) is believed to be the main component responsible for normal endothelial function. Increasing evidence suggests that oxidative stress leading to reduced NO bioavailability and subsequent endothelial dysfunction is an important factor in the progression of vascular diseases. Further investigation of NO metabolites in blood may provide insight into the mechanisms of endothelial dysfunction and disease progression. Preliminary data suggest that although plasma nitrite levels are decreased in CAD patients and correlate with endothelial dysfunction, the nitrite within red blood cells and whole blood is compensatorily increased. Since this new measure is more reproducible and convenient to measure, it may serve as a biomarker of endothelial dysfunction. A prospective study of nitrite and other novel NO-based assays, proteomics, and current biomarkers linked to endothelial function phenotype will allow further investigation into the pathophysiology of endothelial dysfunction and permit development of future markers of atherothrombosis.
Study design
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- The initial study group will consist of 120 subjects, which will consist of 100 subjects with documented CAD (by cardiac catheterization showing greater than or equal to 70% stenosis in an epicardial vessel), previously documented MI (based on ECG or cardiac enzymes) or CAD risk equivalents (diabetes, peripheral vascular disease, abdominal aortic aneurysm, symptomatic carotid disease, or multiple risk factors that confer a 10 year risk of greater than 20% as defined by the Framingham Risk Score) and 20 healthy age- and sex-matched controls.
- Written informed consent.
Key exclusion criteria (9 listed)
- Atrial fibrillation
- Any contraindications to oral nitrates
- Hypotension, bradycardia.
- Myocardial infarction within the prior 30 days
- Symptoms of acute CHF
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 9291445Myerburg RJ, Interian A Jr, Mitrani RM, Kessler KM, Castellanos A. Frequency of sudden cardiac death and profiles of risk. Am J Cardiol. 1997 Sep 11;80(5B):10F-19F. doi: 10.1016/s0002-9149(97)00477-3.
- Background: PubMed 9603539Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998 May 12;97(18):1837-47. doi: 10.1161/01.cir.97.18.1837.
- Background: PubMed 12432042Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002 Nov 14;347(20):1557-65. doi: 10.1056/NEJMoa021993.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
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 3 inclusion and 9 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: finished, as of the sponsor's last update on 2 Jul 2017. 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 United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00109018, which also lists 3 linked publications.
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 2 Jul 2017.