Therapeutic Application of Intravascular Nitrite for Sickle Cell Disease
Status:
Completed
Trial end date:
2007-08-24
Target enrollment:
Participant gender:
Summary
This study examines ways in which nitric oxide (NO), an important molecule that controls how
blood flows through the body's 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 Laboratory/Cardiovascular 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.