A Dose Escalation Study of Intravenous L-citrulline in Steady-state Sickle Cell Disease

Inclusion Criteria: * Sickle cell disease genotypes (HbSS, HbS/β° thalassemia, HbS/β+thalassemia, HbSC) Exclusion Criteria: * Presence of any acute illness defined by fever \>100.4° F within the past 48 hours * Presence of sickle cell pain crisis defined by the presence of pain requiring oral or parental opioid therapy. * 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. * Severe anemia (hemoglobin \< 5g/dL) * History of red blood cell transfusion within the last 14 days * Systemic steroid therapy within the last 48 hours * Pregnant (as confirmed by a negative urine pregnancy test) or lactating female * Alanine/aspartate transferase \>2x upper limit of normal laboratory range for age. * Elevated serum creatinine \>1.5mg/dL * Patients with an inability to give consent will be excluded * Medications that are known to be contra-indicated with use of L-citrulline (concurrent use of hydroxyurea will be allowed). * History of diabetes due to risk of electrolyte imbalance