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