Safety and Efficacy of Sodium Nitrite in Sickle Cell Disease

Nitric oxide (NO) is a naturally occuring chemical that relaxes blood vessels and helps
improve blood flow.

The pain associated with vaso-occlusive crisis (pain crisis) in sickle cell disease is caused
in part by lack of oxygen and increased tissue acid because blood flow is blocked by stiff
sickle red cells. Administration of sodium nitrite should generate nitric oxide in this area
of hypoxia and acidosis and improve blood flow.

Inclusion Criteria:

Subjects meeting all of the following criteria will be considered for admission to the
study:

1. Male or female subject aged between 8 and 23 years of age; only patients up to the age
of 23 will be studied at Childrens Hospital Los Angeles

2. Electrophoretic diagnosis of sickle cell disease;

3. Sudden onset of acute pain involving >=1 sites typical of vaso-occlusive crisis
(Vaso-occlusive crisis is defined as acute, severe pain in the extremities, chest,
abdomen, or back that can not be explained by other complications of sickle cell
disease or by a cause other than sickle cell disease.);

4. Severe pain requiring parenteral analgesics and hospitalization.

5. Informed consent obtained from a legal representative or from subjects 18 years of age
or older before enrollment;

6. Being willing and able to be followed for at least 30 days for evaluation.

Exclusion Criteria:

Subjects presenting with any of the following will not be included in the study:

1. Clinically significant bleeding;

2. Current drug abuse or participation in methadone program;

3. Episode of pain requiring hospitalization within 2 weeks prior to current admission;

4. Other complications of sickle cell disease including cerebrovascular accident,
pulmonary hypertension, or seizure;

5. Pregnancy (confirmed by a serum human chorionic gonadotropin pregnancy test) or breast
feeding;

6. Blood pressure less than 25th percentile for the subject's age and sex on admission or
at the time of screening;

7. Methemoglobinemia >3%;

8. Anemia with hemoglobin level less than 6 g/dL;

9. Red blood cell G6PD deficiency, by laboratory testing prior to enrollment;

10. History of allergy to nitrites or allergy to other substances characterized by dyspnea
and cyanosis;

11. Treatment with allopurinol, a medication that could interfere with nitrite metabolism,
within the past 30 days before screening;

12. Treatment with any investigational drug within the past 30 days;

13. Significant acute or chronic concomitant diseases (including renal, hepatic,
cardiovascular, pulmonary, or oncologic disease, sepsis, pulmonary edema, pulmonary
embolism) that would be inconsistent with survival for at least 6 months;

14. Any subject judged by the clinical investigator or study manager to be inappropriate
for the study.