Ignite Creation Date:
2024-05-05 @ 11:21 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001716
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
1999-11-03
Brief Title:
Effects of Nitric Oxide and Nitroglycerin in Patients With Sickle Cell Anemia
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Physiologic Effects of Inhaled Nitric Oxide Nitroglycerin and Placebo in Study Subjects With Sickle Cell Anemia
Status:
COMPLETED
Status Verified Date:
2003-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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
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 015 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 ie 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 31Phosphorus Magnetic Resonance Spectroscopy 31P-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
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 ie 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 31Phosphorus Magnetic Resonance Spectroscopy 31P-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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 98-CC-0129 | None | None | None |