Hydroxyurea to Prevent Brain Injury in Sickle Cell Disease

Inclusion Criteria for Screening

• Participant must have sickle cell anemia (hemoglobin SS) or sickle Beta-zero (null) thalassemia (hemoglobin S-B0) as confirmed at the local institution by hemoglobin analysis after six months of age.
• Participant must be 9 to 48 months of age. All screening procedures except MRI can be completed between 9 and 12 months of age, with the exception of the MRI, for which the child must have reached the age of 12 months.
• Informed consent must be signed by the participant's legally authorized guardian acknowledging written consent to join the study.

Exclusion Criteria for Screening

• History of a focal neurologic event lasting more than 24 hours with medical documentation or a history of prior overt stroke.
• Other neurological problems, such as neurofibromatosis, lead poisoning, non-febrile seizure disorder, or tuberous sclerosis.
• Known human immunodeficiency virus (HIV) infection.
• Treatment with anti-sickling drugs or hydroxyurea within 3 months or anticipated treatment during the course of the study.
• Chronic blood transfusion therapy, ongoing or planned.
• Poor adherence likely per his/her hematologist and study coordinator based on previous compliance in clinic appointments and following advice.
• Presence or planned permanent (or semi-permanent) metallic structures attached to their body. (e.g., braces on teeth), which their physicians believe will interfere with the MRI of the brain.
• History of two or more TCD studies with a velocity ≥ 200 cm/sec by the non-imaging technique, or ≥185 cm/sec for the imaging technique or a indeterminate TCD.
• Significant cytopenias [absolute neutrophil count (ANC) 9 g/dl]. Cytopenias will be considered transient exclusions.
• Other significant organ system dysfunction
• Known allergy or intolerance of hydroxyurea
• Significant prematurity (gestational age of 38˚ C on the day of sedation
• Upper or lower respiratory infection, active bronchospasm, acute chest syndrome, splenic sequestration or other acute complications of sickle cell disease other than pain in the last 4 weeks (from resolution of symptoms) 9. Pain crisis within two weeks requiring treatment with opiates

Inclusion Criteria for Randomization

• Participant must be 12 to 54 months of age
• Participant must have successfully completed screening procedures (TCD, MRI of the brain, neurology exam, and cognitive evaluation)

Exclusion Criteria for Randomization

• Participants whose MRI show a silent or overt cerebral infarct.
• Participants who have a non-imaging TCD study with a velocity ≥ 185 cm/sec or a TCD that is indeterminate.
• Participants with abnormal kidney function (creatinine > 0.8 mg/dl)
• Significant cytopenias [absolute neutrophil count (ANC) 9 g/dl]. Cytopenias will be considered transient exclusions.