Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00009581
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2001-02-01
Brief Title:
Nitric Oxide to Improve Blood Flow in Sickle Cell Disease
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Targeted Delivery of Nitric Oxide by Hemoglobin to Improve Regional Blood Flow in Sickle Cell Disease
Status:
COMPLETED
Status Verified Date:
2003-01
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:
Nitric oxide is important in regulating blood vessel dilation and consequently blood flow This gas is continuously produced by cells that line the blood vessels It is also transported from the lungs by hemoglobin in red blood cells This study will examine how this gas regulates blood vessels and blood flow in people with sickle cell anemia It will also look at a possible benefit of using certain genetic information to compare the white blood cells of people with sickle cell anemia to those without the disease
Patients with sickle cell anemia and healthy normal volunteers 18 to 65 years of age may be eligible for this study Candidates will be screened with a medical history cardiovascular physical examination electrocardiogram and routine blood tests Participation of volunteers without sickle cell anemia will be limited to a single blood draw for genetic study Sickle cell disease patients will undergo the following procedures
Patients will lie in a reclining chair during the study After administration of a local anesthetic small tubes will be inserted through a needle into the artery and vein of the patients forearm These are used to measure blood pressure and draw blood samples during the study Forearm blood flow will be measured using pressure cuffs placed on the wrist and upper arm and a strain gauge a rubber band device placed around the forearm When the cuffs are inflated blood flows into the arm stretching the strain gauge and the flow measurement is recorded A small lamp will be positioned over the hand Light reflected back from the hand provides information about nitric oxide and hemoglobin in the blood of the skin A squeezing device called a dynamometer will be used to measure handgrip strength
Baseline blood flow nitric oxide hemoglobin and handgrip will be measured after an infusion of glucose sugar and water These measurements will be repeated at various times before during and after administration of small doses of the following drugs
Sodium nitroprusside - causes blood vessels to dilate and increases blood flow to the heart
Acetylcholine - causes blood vessels to dilate and slows heart rate
LNMMA - decreases blood flow by blocking the production of nitric oxide
There will be a 20- to 30-minute rest period between injections of the different drugs
When the above tests are completed the patient will breathe a mixture of room air and nitric oxide for 1 hour through a facemask placed over the face after which forearm blood flow and light reflected from the hand will be measured Then the patient will do the handgrip exercise for 5 minutes after which blood flow and hand lamp measurements will be taken After a 20-minute rest period with continued breathing of room airnitric oxide L-NMMA will be infused again The handgrip exercise blood flow and hand lamp measurements will be repeated The face mask will then be removed and the tubes will be removed 20 minutes later
Blood samples will be collected at various times during the 5- to 6-hour study through the tubes in the arm Some of the blood will be used to look at genes that make proteins involved in cell-to-cell communication inflammation and in making red and white blood cells stick to the lining of blood vessels
Patients with sickle cell anemia and healthy normal volunteers 18 to 65 years of age may be eligible for this study Candidates will be screened with a medical history cardiovascular physical examination electrocardiogram and routine blood tests Participation of volunteers without sickle cell anemia will be limited to a single blood draw for genetic study Sickle cell disease patients will undergo the following procedures
Patients will lie in a reclining chair during the study After administration of a local anesthetic small tubes will be inserted through a needle into the artery and vein of the patients forearm These are used to measure blood pressure and draw blood samples during the study Forearm blood flow will be measured using pressure cuffs placed on the wrist and upper arm and a strain gauge a rubber band device placed around the forearm When the cuffs are inflated blood flows into the arm stretching the strain gauge and the flow measurement is recorded A small lamp will be positioned over the hand Light reflected back from the hand provides information about nitric oxide and hemoglobin in the blood of the skin A squeezing device called a dynamometer will be used to measure handgrip strength
Baseline blood flow nitric oxide hemoglobin and handgrip will be measured after an infusion of glucose sugar and water These measurements will be repeated at various times before during and after administration of small doses of the following drugs
Sodium nitroprusside - causes blood vessels to dilate and increases blood flow to the heart
Acetylcholine - causes blood vessels to dilate and slows heart rate
LNMMA - decreases blood flow by blocking the production of nitric oxide
There will be a 20- to 30-minute rest period between injections of the different drugs
When the above tests are completed the patient will breathe a mixture of room air and nitric oxide for 1 hour through a facemask placed over the face after which forearm blood flow and light reflected from the hand will be measured Then the patient will do the handgrip exercise for 5 minutes after which blood flow and hand lamp measurements will be taken After a 20-minute rest period with continued breathing of room airnitric oxide L-NMMA will be infused again The handgrip exercise blood flow and hand lamp measurements will be repeated The face mask will then be removed and the tubes will be removed 20 minutes later
Blood samples will be collected at various times during the 5- to 6-hour study through the tubes in the arm Some of the blood will be used to look at genes that make proteins involved in cell-to-cell communication inflammation and in making red and white blood cells stick to the lining of blood vessels
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 are common complications of sickle cell anemia Inhaled nitric oxide NO has been proposed as a possible therapy for the acute chest syndrome Anecdotally NO has been described to rapidly improve the hypoxemia and the clinical course of the acute chest syndrome Furthermore a number of recent studies have suggested that NO may have a favorable impact on sickle red cells at the molecular level and could improve the abnormal microvascular perfusion that is characteristic of sickle cell anemia This clinical trial is designed to test the hypotheses that 1 individuals with sickle cell anemia have endothelial dysfunction with reduced local synthesis and release of NO that may reduce regional perfusion at rest and impair the vasodilator response to stress and 2 during NO inhalation delivery of NO bound to hemoglobin will be enhanced and will improve these abnormalities in regional vascular perfusion Studies will be performed on untreated sickle cell anemia patients and on patients managed with chronic hydroxyurea therapy Demonstration of improved regional perfusion with NO therapy could have significant implications for patient management during acute pain crisis and the acute chest syndrome
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 |
|---|---|---|---|
| 01-CC-0078 | None | None | None |