Principal Investigator moved to another institution

Sickle cell disease is a genetic red blood cell disorder that can result in blocking of the small blood vessels from sickle shaped red blood cells. This causes pain, the main feature of sickle cell disease. Also, low amounts of nitric oxide can occur in sickle cell disease, a substance important for widening the blood vessel wall and therefore preventing blockage of the small blood vessels.

Citrulline is a drug that is known to increase nitric oxide. This is a phase I study of citrulline given by mouth to evaluate the safety, tolerability and appropriate dosing of this medication for individuals with sickle cell disease.

Inclusion Criteria:

1. Sickle cell disease genotypes (HbSS, HbS/β-thalassemia
2. HbS/β+thalassemia, HbSC)
3. Patients with sickle cell disease aged 10 to 25 years old
4. Patients ages 10 through 17 years of age, whose parents have signed permission, and who provide signed patient assent themselves
5. Patients 18 through 25 years of age who provide signed consent.

Exclusion Criteria:

1. Presence of any acute illness defined by fever >100.4°F within the past 48 hours
2. Presence of sickle cell pain crisis defined by the presence of pain requiring oral or parental opioid therapy.
3. Presence of acute chest syndrome or presence of any other complication related to sickle cell disease requiring hospitalization such as splenic sequestration, hepatic sequestration, stroke, avascular necrosis of the hip/shoulder, acute priapism, and patients with diabetes etc.
4. Severe anemia (hemoglobin < 5g/dL)
5. History of red blood cell transfusion within the last 14 days
6. Systemic steroid therapy within the last 48 hours
7. Pregnant (as confirmed by a negative urine pregnancy test) or lactating female
8. Alanine/aspartate transferase >2x upper limit of normal laboratory range for age.
9. Elevated serum creatinine: Age 6 to 13 years > 0.9 mg/dL, Age 14-17 years 1.0 mg/dL, Age >18 years >1.5mg/dL
10. Patients with an inability to give assent (ages 10 to 17 years) or consent (ages 18 through 25 years) will be excluded
11. History of diabetes due to risk of electrolyte imbalance