Chest PainPhase 2NCT00001716
Effects of Nitric Oxide and Nitroglycerin in Patients With Sickle Cell Anemia
A Phase 2 study testing Nitric Oxide and Nitroglycerin in people with Chest Pain and Sickle Cell Anemia, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial summary
Sickle cell anemia is the most common genetic disease affecting African-Americans. About 1 in every 1000 African-Americans has the disease and 1 in every 12 carry the genes that could be passed on to their children. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Chest Pain, Sickle Cell Anemia
- What is being tested?
- Nitric Oxide and Nitroglycerin
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 1998to Jul 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
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Males or females 18 to 65 years of age.
- Diagnosis of sickle cell disease (electrophoretic documentation of SS homozygosity is required) or identification as a normal volunteer.
- Hematocrit greater than 18% (with an absolute reticulocyte count greater than 100,000/ml).
- Hematocrit 18-21% (with an absolute reticulocyte count greater than 100,000/ml): Only 100 ml of blood may be drawn. The study subject may be re-entered in the study after four weeks (with repeat full screening labs).
Who cannot join
- Clinically unstable sickle cell anemia defined by the following:
- Having greater than two acute pain crises in the last two months; on hydroxyurea or butyrate therapy any time in the last 12 months; or blood transfusion within last three months, or % hemoglobin A greater than 20%.
- Age less than 18 years or greater than 65 years.
- Current pregnancy or lactation.
- Inability to exercise the anterior tibialis muscle.
- Active cigarette smoker-defined as the inhalation of smoke from any tobacco product in the last one month.
Show all 11Show fewer
- Medical conditions: diabetes mellitus; coronary artery disease; peripheral vascular disease; migraine headaches in the last 12 months; history of previous CVA or stroke; or creatinine greater than 1.0 mg/dL.
- MRI Exclusions: cardiac pacemaker or implantable defibrillator; aneurysm clip; neural stimulator (e.g. TENS-Unit); any type of ear implant; or metal in the eye (e.g. from machining); any implanted device (e.g. insulin pump, drug infusion device); or any metallic foreign body, shrapnel, or bullet.
- Hematocrit less than or equal to 18 percent: will not be eligible for the study; may return for evaluation at a later date.
- No aspirin or non-steroidal anti-inflammatory drugs (no NSAIDS and caffeine the day of the study.) Patients on opiates and acetaminophen will not be excluded.
- Patients taking Viagra will be excluded from the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Warren G. Magnuson Clinical Center (CC)
Bethesda, Maryland, 20892
About this study
Official title: Physiologic Effects of Inhaled Nitric Oxide, Nitroglycerin, and Placebo in Study Subjects With Sickle Cell Anemia
Sickle cell anemia is the most common genetic disease affecting African-Americans. About 1 in every 1000 African-Americans has the disease and 1 in every 12 carry the genes that could be passed on to their children. People with sickle cell anemia have abnormal hemoglobin, the molecules responsible for carrying oxygen in the blood. The abnormal hemoglobin can cause damage to the red blood cells. The damaged red blood cell may then stick in the blood vessels and cause pain and injury to organs. Some of the complications caused by the sticking of blood cells are called acute pain crisis and acute chest syndrome (ACS).
Nitric oxide (NO) is a gas that has been proposed as a possible therapy for the ACS complication of sickle cell anemia. Studies have shown that NO may favorably affect sickle cell hemoglobin molecules, thereby improving blood flow through small vessels.
This study is designed to evaluate the effects of NO, when taken in combination with a drug called nitroglycerin on patients with sickle cell anemia and normal volunteers. The effects of these two drugs only last while the patient is receiving them. Researchers hope the information learned from this study will help to develop new therapies for sickle cell anemia.
Read the detailed description
Sickle cell anemia is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Approximately 0.15% of African-Americans are homozygous for sickle cell disease, and 8% have sickle cell trait. Acute pain crisis and acute chest syndrome (ACS) are common complications of sickle cell anemia. Inhaled nitric oxide (NO) has been proposed as a possible therapy for the ACS. Anecdotally, NO has been described to rapidly improve the hypoxemia and the clinical course of the ACS. Furthermore, a number of recent studies have suggested that NO may have a favorable impact on sickle hemoglobin at the molecular level and could improve the abnormal microvascular perfusion that is characteristic of sickle cell anemia.
This clinical trial is designed to evaluate the physiologic and molecular effects of inhaled NO and a currently available, safe, FDA-approved medication, nitroglycerin, that is a nitric oxide donor (i.e., a source of NO after metabolism in the body), in study subjects with and without sickle cell anemia. Whole blood will be analyzed to characterize the metabolism of NO and NO donors, the molecular interactions between hemoglobin and NO, the duration of effect of these therapies on hemoglobin oxygen affinity and other properties of the erythrocyte and intracellular hemoglobin (including the solubility of deoxy sickle hemoglobin).
We also plan to characterize the effect of NO delivery on microvascular perfusion in study subjects with and without sickle cell anemia. Measurements in study subjects will be made prior to and while receiving either NO, nitroglycerin, or placebo. These perfusion measurements will occur at rest and during concentric dorsiflexion exercise. Magnetic resonance imaging (MRI) of lower extremity skeletal muscle enhancement during first passage of intravenously injected gadolinium contrast will be used to evaluate regional skeletal muscle perfusion. Perfusion measurements will be paired with a [31]Phosphorus Magnetic Resonance Spectroscopy ([31]P-MRS) study of the concentration of muscle high energy phosphate compounds. Changes in their levels reflect the energy state of muscle and are dependent on the adequacy of blood flow.
This study will allow three major assessments: firstly, the characterization of the microvascular perfusion at rest and during exercise in study subjects with sickle cell anemia. Secondly, the effects of NO on red cell and hemoglobin function and skeletal muscle perfusion in normal study subjects (without sickle cell anemia), and finally, the effects of NO on red cell and hemoglobin function and skeletal muscle perfusion in study subjects with sickle cell anemia. Our hypothesis is that one or more of these effects could be of potential therapeutic benefit to sickle cell anemia patients.
- Conditions
- Chest Pain, Sickle Cell Anemia
- Being tested
- Nitric Oxide, Nitroglycerin
- Keywords
- Hemoglobin, P50, Microvascular, Perfusion, Magnetic Resonance Imaging, Sickle Cell Anemia
- Medical subject headings
- Chest Pain, Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric OxideDrug
NitroglycerinDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startJul 1998
- Study completionJul 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 Chest PainStudies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 58 participants
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001716
- Sponsor's protocol ID
- 980129
- Other IDs
- 98-CC-0129
- Status last verified
- Jul 2003
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med. 1997 Sep 11;337(11):762-9. doi: 10.1056/NEJM199709113371107. No abstract available.
PubMed 9287233Head CA, Brugnara C, Martinez-Ruiz R, Kacmarek RM, Bridges KR, Kuter D, Bloch KD, Zapol WM. Low concentrations of nitric oxide increase oxygen affinity of sickle erythrocytes in vitro and in vivo. J Clin Invest. 1997 Sep 1;100(5):1193-8. doi: 10.1172/JCI119631.
PubMed 9276736Gow AJ, Stamler JS. Reactions between nitric oxide and haemoglobin under physiological conditions. Nature. 1998 Jan 8;391(6663):169-73. doi: 10.1038/34402.
PubMed 9428761
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
- Physiologic Effects of Inhaled Nitric Oxide, Nitroglycerin, and Placebo in Study Subjects With Sickle Cell Anemia
- ClinicalTrials.gov ID
- NCT00001716
- Acronym / sponsor ID
- 980129
- Conditions
- Chest Pain, Sickle Cell Anemia
- Keywords
- Hemoglobin, P50, Microvascular, Perfusion, Magnetic Resonance Imaging, Sickle Cell Anemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Study start
- Jul 1998
- Study completion
- Jul 2003
- First posted
- 4 Nov 1999 (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.
Sickle cell anemia is the most common genetic disease affecting African-Americans. About 1 in every 1000 African-Americans has the disease and 1 in every 12 carry the genes that could be passed on to their children. People with sickle cell anemia have abnormal hemoglobin, the molecules responsible for carrying oxygen in the blood. The abnormal hemoglobin can cause damage to the red blood cells. The damaged red blood cell may then stick in the blood vessels and cause pain and injury to organs. Some of the complications caused by the sticking of blood cells are called acute pain crisis and acute chest syndrome (ACS).
Nitric oxide (NO) is a gas that has been proposed as a possible therapy for the ACS complication of sickle cell anemia. Studies have shown that NO may favorably affect sickle cell hemoglobin molecules, thereby improving blood flow through small vessels.
This study is designed to evaluate the effects of NO, when taken in combination with a drug called nitroglycerin on patients with sickle cell anemia and normal volunteers. The effects of these two drugs only last while the patient is receiving them. Researchers hope the information learned from this study will help to develop new therapies for sickle cell anemia.
Detailed description
Sickle cell anemia is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Approximately 0.15% of African-Americans are homozygous for sickle cell disease, and 8% have sickle cell trait. Acute pain crisis and acute chest syndrome (ACS) are common complications of sickle cell anemia. Inhaled nitric oxide (NO) has been proposed as a possible therapy for the ACS. Anecdotally, NO has been described to rapidly improve the hypoxemia and the clinical course of the ACS. Furthermore, a number of recent studies have suggested that NO may have a favorable impact on sickle hemoglobin at the molecular level and could improve the abnormal microvascular perfusion that is characteristic of sickle cell anemia.
This clinical trial is designed to evaluate the physiologic and molecular effects of inhaled NO and a currently available, safe, FDA-approved medication, nitroglycerin, that is a nitric oxide donor (i.e., a source of NO after metabolism in the body), in study subjects with and without sickle cell anemia. Whole blood will be analyzed to characterize the metabolism of NO and NO donors, the molecular interactions between hemoglobin and NO, the duration of effect of these therapies on hemoglobin oxygen affinity and other properties of the erythrocyte and intracellular hemoglobin (including the solubility of deoxy sickle hemoglobin).
We also plan to characterize the effect of NO delivery on microvascular perfusion in study subjects with and without sickle cell anemia. Measurements in study subjects will be made prior to and while receiving either NO, nitroglycerin, or placebo. These perfusion measurements will occur at rest and during concentric dorsiflexion exercise. Magnetic resonance imaging (MRI) of lower extremity skeletal muscle enhancement during first passage of intravenously injected gadolinium contrast will be used to evaluate regional skeletal muscle perfusion. Perfusion measurements will be paired with a [31]Phosphorus Magnetic Resonance Spectroscopy ([31]P-MRS) study of the concentration of muscle high energy phosphate compounds. Changes in their levels reflect the energy state of muscle and are dependent on the adequacy of blood flow.
This study will allow three major assessments: firstly, the characterization of the microvascular perfusion at rest and during exercise in study subjects with sickle cell anemia. Secondly, the effects of NO on red cell and hemoglobin function and skeletal muscle perfusion in normal study subjects (without sickle cell anemia), and finally, the effects of NO on red cell and hemoglobin function and skeletal muscle perfusion in study subjects with sickle cell anemia. Our hypothesis is that one or more of these effects could be of potential therapeutic benefit to sickle cell anemia patients.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Males or females 18 to 65 years of age.
- Diagnosis of sickle cell disease (electrophoretic documentation of SS homozygosity is required) or identification as a normal volunteer.
- Hematocrit greater than 18% (with an absolute reticulocyte count greater than 100,000/ml).
- Hematocrit 18-21% (with an absolute reticulocyte count greater than 100,000/ml): Only 100 ml of blood may be drawn. The study subject may be re-entered in the study after four weeks (with repeat full screening labs).
Key exclusion criteria (11 listed)
- Having greater than two acute pain crises in the last two months; on hydroxyurea or butyrate therapy any time in the last 12 months; or blood transfusion within last three months, or % hemoglobin A greater than 20%.
- Age less than 18 years or greater than 65 years.
- Current pregnancy or lactation.
- Inability to exercise the anterior tibialis muscle.
- Active cigarette smoker-defined as the inhalation of smoke from any tobacco product in the last one month.
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 | Drug | – |
| Nitroglycerin | 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 9287233Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med. 1997 Sep 11;337(11):762-9. doi: 10.1056/NEJM199709113371107. No abstract available.
- Background: PubMed 9276736Head CA, Brugnara C, Martinez-Ruiz R, Kacmarek RM, Bridges KR, Kuter D, Bloch KD, Zapol WM. Low concentrations of nitric oxide increase oxygen affinity of sickle erythrocytes in vitro and in vivo. J Clin Invest. 1997 Sep 1;100(5):1193-8. doi: 10.1172/JCI119631.
- Background: PubMed 9428761Gow AJ, Stamler JS. Reactions between nitric oxide and haemoglobin under physiological conditions. Nature. 1998 Jan 8;391(6663):169-73. doi: 10.1038/34402.
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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 Nitroglycerin in people with Chest Pain and Sickle Cell Anemia, run by National Institutes of Health Clinical Center (CC) 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 4 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 NCT00001716, 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.