Effects of Nitric Oxide and Nitroglycerin in Patients With Sickle Cell Anemia
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00001716|
Recruitment Status : Completed
First Posted : November 4, 1999
Last Update Posted : March 4, 2008
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.
|Condition or disease||Intervention/treatment||Phase|
|Chest Pain Sickle Cell Anemia||Drug: Nitric Oxide Drug: Nitroglycerin||Phase 2|
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 Phosphorus Magnetic Resonance Spectroscopy (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 Type :||Interventional (Clinical Trial)|
|Enrollment :||58 participants|
|Official Title:||Physiologic Effects of Inhaled Nitric Oxide, Nitroglycerin, and Placebo in Study Subjects With Sickle Cell Anemia|
|Study Start Date :||July 1998|
|Study Completion Date :||July 2003|
U.S. FDA Resources
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001716
|United States, Maryland|
|Warren G. Magnuson Clinical Center (CC)|
|Bethesda, Maryland, United States, 20892|