Patient description: The patient is a 34-year-old African American man with the known history of Sickle cell disease comes to the clinic with severe bone pain. The patient had severe pain in his lower back that radiated to both thighs scored 9 out of 10. The patient has had positive history of sickle cell crises since childhood. He also had the same symptoms in past two weeks treated with oxycodone which was not beneficial to his pain. His PCP sent him to the emergency department to receive intra venous pain modulators. The patient is afebrile within the normal blood pressure. No splenomegaly was detected in the physical exam. He has no positive history of drug allergy. He won't smoke or uses any illicit drugs. The lab study is as bellow: Hgb: 8 g/dl WBC: 10000 /mm3 Plt: 300000 /ml MCV: 106 fL Hemoglobine electrophoresis: 91% HbS 6%HbF 3%HbA2 AST: 22 U/L ALT: 43 U/L Alk P: 53 U/L Ferritin: 1200 ng/ml

Clinical trial eligibility criteria: eligible ages (years): 6.0-21.0,  Acute Vaso Occlusive Crisis (VOC) Sickle cell disease (all genotypes) 2. Children, adolescents and young adults between ages 6 to 21 years 3. In a steady disease state and not in the midst of any acute complication other than VOC due to sickle cell disease at study entry 4. For female of childbearing potential, a negative urine pregnancy test and using an adequate method of contraception, or denies sexual activity 5. Subjects or parents or legal guardian of the subject who are willing and able to sign and provide consent and assent (where appropriate for the age of the child)  Current pain lasting >3 days 2. >6 hospital admissions in the prior year 3. History of opioid dependence/substance abuse 4. Has been on a clinical trial of a new therapy for sickle cell disease within the last 3 months 5. Presence of any other complication related to sickle cell disease such as splenic sequestration, hepatic sequestration, stroke, avascular necrosis of the hip/shoulder, acute priapism, renal dysfunction, dactylitis, acute chest syndrome and other major medical conditions or organ dysfunction 6. Severe anemia (hemoglobin <6 g/dL) 7. History of red blood cell transfusion within the last 30 days 8. Systemic steroid therapy within the last 48 hours 9. Pregnancy or lactation (subjects must have a negative urine pregnancy test) 10. Serum creatinine levels: 1. Age 6 to 13 years >0.9 mg/dL 2. Age 14 to 17 years >1.0 mg/dL 3. Age >18 years >1.5 mg/dL 11. Report of fever (>38°C) within last 48 hours 12. Presence of acute chest syndrome, sepsis, bacterial infection, hemodynamic instability 13. Subjects with inability to have parental assent given (ages 6 to 17 years) or consent (ages 18 through 21 years). Note: Parents or legal guardians can provide consent for subjects who are unable to provide assent (eg, sleepy or preoccupied by their pain). 14. History of allergic reaction to L-citrulline product 15. Medications that are known to be contra-indicated with use of L-citrulline 16. History of diabetes. 17. Subjects with a baseline prothrombin time International Normalized ratio (INR) >2.0. 18. Received any blood products within 3 weeks of the screening visit. 19. Unreliable venous access 20. The PI considers that the subject will be unable to comply with the study requirements