Ignite Creation Date:
2024-05-05 @ 11:38 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00095472
Status:
COMPLETED
Last Update Posted:
2019-11-05
First Post:
2004-11-04
Brief Title:
Therapeutic Application of Intravascular Nitrite for Sickle Cell Disease
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Therapeutic Application of Intravascular Nitrite for Sickle Cell Disease
Status:
COMPLETED
Status Verified Date:
2015-12-07
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:
This study examines ways in which nitric oxide NO an important molecule that controls how blood flows through the bodys vessels might be restored with a compound called sodium nitrite It is hoped that the result will reverse the effect of decreased flow of blood due to sickled cells-that is cells that have changed into the shape of a crescent or sickle Sickle cell disease is the most common genetic disease affecting African Americans About 8 of that population has the sickle cell trait The changed cells can become attached to blood vessels decreasing blood flow to vital organs There can be the loss of needed proteins including hemoglobin that deliver oxygen throughout the body
Adults at least 18 years of age who have the SS form of sickle cell disease or S-beta-thalassemia are in either a steady state or crisis give informed and written consent for participation and have had a negative pregnancy test may be eligible for this study Adults with any other disease that puts them at risk for reduced circulation are not eligible Women who are breastfeeding are not eligible
Participants will undergo a medical history including family medical history and a detailed physical evaluation to take about 1 hour There will be a collection of blood echocardiogram which involves taking a picture of the heart and its four chambers and measurement of exhaled carbon monoxide carbon dioxide and NO A procedure called orthogonal polarization spectral imaging will be performed A small object the size of a Popsicle stick will be placed under the tongue or on a fingertip This procedure presents a picture of blood flow and how the red blood cells appear as they circulate through blood vessels The study will be conducted in the Vascular LaboratoryCardiovascular Floor or Intensive Care and will last about 4 hours
During the study patients will lie in an adjustable reclining bed and chair Small tubes will be placed in the artery and vein of the forearm at the inside of the elbow A small pressure cuff will be applied to the wrist and a larger one to the upper arm Both cuffs will be inflated with air A strain gauge resembling a rubber band will go around the widest part of the forearm When the pressure cuffs fill with air blood will flow into the arm and information from the strain gauge will be recorded Between administrations of each medicine there will be 30-minute rests Normal saline will be put into the small tube in the artery Measurements of the blood flow in the forearm will be taken and a small blood sample will be taken to measure blood counts proteins and other natural body chemicals Then a medicine called sodium nitroprusside which causes blood vessels to expand and increase blood flow will be placed into the forearm It will be given at three different doses for 3 minutes each with measurements recorded after each dose Then a medicine called L-NMMA will be placed into the forearm L-NMMA generally decreases local blood flow by preventing nitric oxide from being produced in the cells lining the blood vessels It will be given at two different doses for 5 minutes each with blood flow measured after each dose Next nitrite will be placed in the forearm at three different doses for 5 minutes each Before and after nitrite is given the researchers will measure the amount of the NO carbon monoxide and carbon dioxide that the patients breathe out Then the procedure for administering normal saline sodium nitroprusside and L-NMMA will be repeated as will a blood test
This study will not have a direct benefit for participants However it is hoped that the information gained from the study will help to develop treatment options for patients with sickle cell disease
Adults at least 18 years of age who have the SS form of sickle cell disease or S-beta-thalassemia are in either a steady state or crisis give informed and written consent for participation and have had a negative pregnancy test may be eligible for this study Adults with any other disease that puts them at risk for reduced circulation are not eligible Women who are breastfeeding are not eligible
Participants will undergo a medical history including family medical history and a detailed physical evaluation to take about 1 hour There will be a collection of blood echocardiogram which involves taking a picture of the heart and its four chambers and measurement of exhaled carbon monoxide carbon dioxide and NO A procedure called orthogonal polarization spectral imaging will be performed A small object the size of a Popsicle stick will be placed under the tongue or on a fingertip This procedure presents a picture of blood flow and how the red blood cells appear as they circulate through blood vessels The study will be conducted in the Vascular LaboratoryCardiovascular Floor or Intensive Care and will last about 4 hours
During the study patients will lie in an adjustable reclining bed and chair Small tubes will be placed in the artery and vein of the forearm at the inside of the elbow A small pressure cuff will be applied to the wrist and a larger one to the upper arm Both cuffs will be inflated with air A strain gauge resembling a rubber band will go around the widest part of the forearm When the pressure cuffs fill with air blood will flow into the arm and information from the strain gauge will be recorded Between administrations of each medicine there will be 30-minute rests Normal saline will be put into the small tube in the artery Measurements of the blood flow in the forearm will be taken and a small blood sample will be taken to measure blood counts proteins and other natural body chemicals Then a medicine called sodium nitroprusside which causes blood vessels to expand and increase blood flow will be placed into the forearm It will be given at three different doses for 3 minutes each with measurements recorded after each dose Then a medicine called L-NMMA will be placed into the forearm L-NMMA generally decreases local blood flow by preventing nitric oxide from being produced in the cells lining the blood vessels It will be given at two different doses for 5 minutes each with blood flow measured after each dose Next nitrite will be placed in the forearm at three different doses for 5 minutes each Before and after nitrite is given the researchers will measure the amount of the NO carbon monoxide and carbon dioxide that the patients breathe out Then the procedure for administering normal saline sodium nitroprusside and L-NMMA will be repeated as will a blood test
This study will not have a direct benefit for participants However it is hoped that the information gained from the study will help to develop treatment options for patients with sickle cell disease
Detailed Description:
Sickle cell disease 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 Hemoglobin S polymerization leads to red cell rigidity microvascular obstruction inflammation and end-organ ischemia-reperfusion injury and infarction Our published data indicate that up to 50 of sickle cell patients have endothelial dysfunction due to impaired bioavailability of endogenous nitric oxide due in large part to scavenging of nitric oxide by cell-free plasma hemoglobin These data suggest that therapies directed at restoring NO bioavailability might prove beneficial We have recently discovered that the nitrite anion available currently for human use as a component of the cyanide antidote kit is a vasodilator in vivo by generating nitric oxide NO in tissues with lower oxygen tension and pH The mechanism involves a novel physiological function of human hemoglobin as an oxygen- and pH dependent nitrite reductase To date we have observed that nitrite infusions in animal models significantly reduce liver and cardiac ischemia-reperfusion injury and infarction in mouse models prevent cerebral vasospasm after subarachnoid hemorrhage in primates and decrease pulmonary hypertension in newborn hypoxic sheep The current protocol is designed as a phase III trial to address the hypothesis that nitrite infusions will vasodilate the circulation in patients with sickle cell disease at rest and during vaso-occlusive pain crisis inactivate circulating cell-free plasma hemoglobin reduce pulmonary artery pressures and reduce ischemia-reperfusion injury measured by circulating markers of oxidant stress
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 |
|---|---|---|---|
| 05-H-0016 | None | None | None |