Coronary DiseasePhase 2NCT00014040
Nitric Oxide Inhalation Therapy to Relieve Chest Pain in Patients With Coronary Artery Disease
A Phase 2 study testing Nitric Oxide and INOpulse Delivery System in people with Coronary Disease and Myocardial Ischemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
This study will test whether inhaling nitric oxide gas can improve blood flow to the heart, ventricular function, exercise tolerance in patients with coronary artery disease and chest pain that has not improved with medical or surgical therapy. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Coronary Disease, Myocardial Ischemia
- What is being tested?
- Nitric Oxide and INOpulse Delivery System
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2001to Apr 2003
- Phase
- Phase 2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Presence of angiographically determined CAD.
- At least 1 attempt at revascularization by catheter-based technique or by surgery.
- Myocardial ischemia as determined by stress echocardiography.
- Canadian Cardiovascular Society functional class II or III angina pectoris despite conventional medical management.
- Left ventricular ejection fraction greater than 30% (assessed by radionuclide angiography or by echocardiography).
- Subject understands protocol and provides written, informed consent in addition to willingness to comply with specified follow-up evaluations.
Who cannot join
- Left ventricular ejection fraction less than 30%.
- Active cigarette smoker.
- History of congestive heart failure.
- History of bronchospasm requiring treatment.
- Cardiac disease in addition to CAD (e.g. hypertrophic or dilated cardiomyopathy, valvular heart disease) as determined by echocardiography.
- Angina pectoris at rest, prolonged in duration (greater than 20 minutes), or does not respond to nitroglycerin (2 tablets) during 2 months prior to study.
Show all 11Show fewer
- Evidence of extra-cardiac disease other than diabetes mellitus as determined by physical examination and screening lab work (e.g., creatinine greater than 1.5x upper limit of reference, liver enzymes greater than 2x upper limit of reference, hemoglobin less than 10 g/dL).
- Patients who are HIV positive, have chronic inflammatory diseases, or are on chronic immunosuppressive medications.
- Women of childbearing age unless recent pregnancy test is negative.
- Lactating women.
- Age less than 21 years.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, 20892
About this study
Official title: Nitric Oxide Inhalation Therapy for Myocardial Ischemia in Patients With Coronary Artery Disease
This study will test whether inhaling nitric oxide gas can improve blood flow to the heart, ventricular function, exercise tolerance in patients with coronary artery disease and chest pain that has not improved with medical or surgical therapy.
Patients with coronary artery disease who have chest pain despite treatment with medicines and angioplasty or surgery may be eligible for this study. Those enrolled will receive monetary compensation for their participation in this study.
Read more
The duration of the study is 5 days, with 2 testing periods lasting 2 days each. During one of the periods, the study participants will breathe nitric oxide mixed with room air through a face mask during the tests. During the other period, the participants will breathe room air alone through a face mask during the tests. At least 1 day will separate the treatment periods. During each of the 2 treatment periods (nitric oxide and room air), participants will undergo 4 tests to determine whether the treatment improves the heart's response to stress with increased heart rate and contraction. Approximately one hour before each of the tests, participants will breathe either nitric oxide mixed with room air or room air alone through the face mask, and continue the inhalation treatment while each test is being performed. The face mask will be removed at the end of each test.
On the morning of the first day of each treatment period, participants will have a special echocardiogram with imaging of the heart. The echocardiogram will be performed during an infusion of dobutamine, a medicine that increases heart rate and contraction, and serves to stress the heart. This manner of stress testing is commonly used in hospitals around the country to determine if walls of the heart are receiving sufficient blood supply. That afternoon, participants will undergo a magnetic resonance imaging (MRI) study of the heart. The MRI will determine the heart's blood flow and contraction while receiving the same dosage of dobutamine as was used earlier in the day. On the morning of the second day of each treatment period, participants will exercise on a treadmill until moderately uncomfortable chest pain is reported. Later that morning, participants will undergo cardiac catheterization. For the cardiac catheterization, a long tube (catheter) will be placed into a vein of the neck once the skin is numbed with xylocaine. This tube will be positioned within the right atrium of the heart and into a tube-like structure called the coronary sinus, where venous blood exits the heart muscle. A small catheter will also be placed in an artery of the upper forearm after the skin has been numbed with xylocaine. Blood samples will be taken to allow us to measure the amount of nitric oxide transported in the blood. The blood samples will be drawn (through the tube in the heart and through the small tube in the artery) at the beginning of the study and during infusion of dobutamine to stress the heart. The dose of the dobutamine infusion will be the same dose used in the previous day's stress studies.
After the completion of the first treatment period, we will stop testing for at least one day. Participants will begin the second treatment period with the inhalation treatment not received during the first treatment period.
Read the detailed description
Although medical therapy and revascularization procedures are effective for relief of chest pain symptoms in many patients with coronary artery disease (CAD), others either do not respond to or tolerate medical therapies, or have failed attempts at revascularization. For this growing number of patients, there is a need for novel therapeutic approaches. The purpose of this protocol is to test the effectiveness of nitric oxide (NO) inhalation therapy for the relief of inducible myocardial ischemia in patients with CAD who have failed conventional attempts at medical and revascularization management. Our hypothesis is that enriched NO transport in blood from the lungs and delivery to the coronary vasculature with NO inhalation will improve blood flow to the myocardium during stress by dilating coronary arteries and arterioles. The primary end-point of this study is improvement in treadmill exercise duration during NO inhalation compared with exercise duration during room air breathing, with secondary end-points selected to provide mechanistic insight as to relief of inducible ischemia by NO, including effects on: 1) arterial delivery and myocardial extraction of NO transport molecules, 2) myocardial perfusion, and 3) global and regional myocardial contractility. This clinical trial is randomized, double-blind, and placebo (room air)-controlled in design, with CAD patients treated with NO (or room air) breathing for approximately 1 hour before each stress test, followed by crossover to the alternate therapy after two days of testing. Demonstration of benefit from NO inhalation could result in an important therapeutic option for CAD patients with few alternatives for the relief of myocardial ischemia.
- Conditions
- Coronary Disease, Myocardial Ischemia
- Being tested
- Nitric Oxide and INOpulse Delivery System
- Keywords
- Angina Pectoris, Endothelium, Platelets, Inflammation, Atherosclerosis, Coronary Artery Disease, Chest Pain, Nitrous Oxide Inhalation, Treadmill Exercise
- Medical subject headings
- Coronary Disease, Myocardial Ischemia, Angina Pectoris, Inflammation, Atherosclerosis, Coronary Artery Disease, Chest Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric Oxide and INOpulse Delivery SystemDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2001 (estimated)
- Study startApr 2001
- Study completionApr 2003
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 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 25 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00014040
- Sponsor's protocol ID
- 010140
- Other IDs
- 01-H-0140
- Status last verified
- Apr 2003
- First submitted
- 7 Apr 2001
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun 16;333(6174):664-6. doi: 10.1038/333664a0.
PubMed 3131684Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11-17;327(6122):524-6. doi: 10.1038/327524a0.
PubMed 3495737Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373-6. doi: 10.1038/288373a0.
PubMed 6253831
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nitric Oxide Inhalation Therapy for Myocardial Ischemia in Patients With Coronary Artery Disease
- ClinicalTrials.gov ID
- NCT00014040
- Acronym / sponsor ID
- 010140
- Conditions
- Coronary Disease, Myocardial Ischemia
- Keywords
- Angina Pectoris, Endothelium, Platelets, Inflammation, Atherosclerosis, Coronary Artery Disease, Chest Pain, Nitrous Oxide Inhalation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Apr 2001
- Study completion
- Apr 2003
- First posted
- 9 Apr 2001 (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.
This study will test whether inhaling nitric oxide gas can improve blood flow to the heart, ventricular function, exercise tolerance in patients with coronary artery disease and chest pain that has not improved with medical or surgical therapy.
Patients with coronary artery disease who have chest pain despite treatment with medicines and angioplasty or surgery may be eligible for this study. Those enrolled will receive monetary compensation for their participation in this study.
The duration of the study is 5 days, with 2 testing periods lasting 2 days each. During one of the periods, the study participants will breathe nitric oxide mixed with room air through a face mask during the tests. During the other period, the participants will breathe room air alone through a face mask during the tests. At least 1 day will separate the treatment periods. During each of the 2 treatment periods (nitric oxide and room air), participants will undergo 4 tests to determine whether the treatment improves the heart's response to stress with increased heart rate and contraction. Approximately one hour before each of the tests, participants will breathe either nitric oxide mixed with room air or room air alone through the face mask, and continue the inhalation treatment while each test is being performed. The face mask will be removed at the end of each test.
On the morning of the first day of each treatment period, participants will have a special echocardiogram with imaging of the heart. The echocardiogram will be performed during an infusion of dobutamine, a medicine that increases heart rate and contraction, and serves to stress the heart. This manner of stress testing is commonly used in hospitals around the country to determine if walls of the heart are receiving sufficient blood supply. That afternoon, participants will undergo a magnetic resonance imaging (MRI) study of the heart. The MRI will determine the heart's blood flow and contraction while receiving the same dosage of dobutamine as was used earlier in the day. On the morning of the second day of each treatment period, participants will exercise on a treadmill until moderately uncomfortable chest pain is reported. Later that morning, participants will undergo cardiac catheterization. For the cardiac catheterization, a long tube (catheter) will be placed into a vein of the neck once the skin is numbed with xylocaine. This tube will be positioned within the right atrium of the heart and into a tube-like structure called the coronary sinus, where venous blood exits the heart muscle. A small catheter will also be placed in an artery of the upper forearm after the skin has been numbed with xylocaine. Blood samples will be taken to allow us to measure the amount of nitric oxide transported in the blood. The blood samples will be drawn (through the tube in the heart and through the small tube in the artery) at the beginning of the study and during infusion of dobutamine to stress the heart. The dose of the dobutamine infusion will be the same dose used in the previous day's stress studies.
After the completion of the first treatment period, we will stop testing for at least one day. Participants will begin the second treatment period with the inhalation treatment not received during the first treatment period.
Detailed description
Although medical therapy and revascularization procedures are effective for relief of chest pain symptoms in many patients with coronary artery disease (CAD), others either do not respond to or tolerate medical therapies, or have failed attempts at revascularization. For this growing number of patients, there is a need for novel therapeutic approaches. The purpose of this protocol is to test the effectiveness of nitric oxide (NO) inhalation therapy for the relief of inducible myocardial ischemia in patients with CAD who have failed conventional attempts at medical and revascularization management. Our hypothesis is that enriched NO transport in blood from the lungs and delivery to the coronary vasculature with NO inhalation will improve blood flow to the myocardium during stress by dilating coronary arteries and arterioles. The primary end-point of this study is improvement in treadmill exercise duration during NO inhalation compared with exercise duration during room air breathing, with secondary end-points selected to provide mechanistic insight as to relief of inducible ischemia by NO, including effects on: 1) arterial delivery and myocardial extraction of NO transport molecules, 2) myocardial perfusion, and 3) global and regional myocardial contractility. This clinical trial is randomized, double-blind, and placebo (room air)-controlled in design, with CAD patients treated with NO (or room air) breathing for approximately 1 hour before each stress test, followed by crossover to the alternate therapy after two days of testing. Demonstration of benefit from NO inhalation could result in an important therapeutic option for CAD patients with few alternatives for the relief of myocardial ischemia.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Presence of angiographically determined CAD.
- At least 1 attempt at revascularization by catheter-based technique or by surgery.
- Myocardial ischemia as determined by stress echocardiography.
- Canadian Cardiovascular Society functional class II or III angina pectoris despite conventional medical management.
- Left ventricular ejection fraction greater than 30% (assessed by radionuclide angiography or by echocardiography).
Key exclusion criteria (11 listed)
- Left ventricular ejection fraction less than 30%.
- Active cigarette smoker.
- History of congestive heart failure.
- History of bronchospasm requiring treatment.
- Cardiac disease in addition to CAD (e.g. hypertrophic or dilated cardiomyopathy, valvular heart disease) as determined by echocardiography.
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 |
|---|---|---|
| Nitric Oxide and INOpulse Delivery System | Drug | – |
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 4 Mar 2008.
- Background: PubMed 3131684Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun 16;333(6174):664-6. doi: 10.1038/333664a0.
- Background: PubMed 3495737Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11-17;327(6122):524-6. doi: 10.1038/327524a0.
- Background: PubMed 6253831Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373-6. doi: 10.1038/288373a0.
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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?
A Phase 2 study testing Nitric Oxide and INOpulse Delivery System in people with Coronary Disease and Myocardial Ischemia, 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 6 inclusion and 11 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 4 Mar 2008. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 NCT00014040, 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 4 Mar 2008.