This study will determine the dose of sodium nitrite that can safely be used to prevent
constriction, or tightening, of the arteries. Narrowed arteries in the brain can cause
stroke. Animal studies show that nitrite injections improve blood flow and that injections
over long periods of time prevent damage to the arteries in the brain; however, there is no
information on the effects of prolonged nitrite infusion in humans. This study will establish
the safe dose and side effects of nitrite infusion in humans.
Healthy normal volunteers between 21 and 60 years of age may be eligible for this study.
Candidates are screened for high or low blood pressure, aspirin use, pregnancy, and blood
levels of nitrite and methemoglobin (a substance that temporarily and slightly lowers the
oxygen carried in the red blood cells). Pregnant women are excluded from the study.
Participants are admitted to the Clinical Center for 16 1/4 days, the first 2 days in the
hospital's intensive care unit (ICU). Upon admission they provide a medical history, have
physical and cardiovascular examinations, and blood tests. For the infusion procedure, a
catheter (thin plastic tube) is inserted into an artery in the wrist or the crease of the
elbow to measure blood pressure, and catheters are placed in a vein in each arm for
administering the nitrite and withdrawing blood samples.
In the morning of day 1, after initial blood pressure and heart rate measurements are taken
and a blood sample is drawn, a saline (salt water) infusion is started. Blood pressure and
heart rate are monitored every 30 minutes for 6 hours, then every hour for 6 hours, then
every 2 hours for 12 hours. Blood samples are collected every 4 hours for 24 hours. On day 2,
the sodium nitrite infusion begins. Blood pressure and methemoglobin are monitored every 10
minutes for the first 2 hours. If blood pressure remains stable, the frequency of
measurements is decreased to every 30 minutes for 4 hours, then every 1 hour for the next 6
hours, and then every 4 hours for 12 hours. If the pressure continues to remain stable,
monitoring continues every 8 hours for the rest of the study. Blood is drawn periodically
from the catheter to determine the amount of nitrite and methemoglobin in the body, with
decreasing frequency from several times during the first hour of the infusion to every 24
hours. After the first 24 to 48 hours of the nitrite infusion, participants are transferred
from the ICU to a general nursing unit fo...
Phase:
Phase 1
Details
Lead Sponsor:
National Institute of Neurological Disorders and Stroke (NINDS)