Sickle cell disease (SCD) is a genetic disease characterized by abnormal hemoglobin, the main constituent of red blood cells. People with SCD have nutritional deficiencies, and vitamin D deficiency is one of the most common. Symptoms of vitamin D deficiency are similar to those of SCD and include chronic pain and bone complications. Correcting vitamin D nutrition of children with SCD represents a treatment that will improve their health. A single oral high-dose of vitamin D3 will be given to SCD children during one of their follow-up visits at the SCD clinic of CHU Sainte-Justine, Montreal, Canada. This mode of administration was chosen to ensure a better adherence to the treatment. The investigators will determine whether this dose is safe and its administration feasible in clinic. The impact of this dose on blood vitamin D and calcium, urinary calcium, growth, inflammation, bone health, pain and quality of life will also be assessed. This study intends to propose a new intervention to improve the nutrition of children with this disease.

Vitamin D deficiency is one of the most common nutritional conditions among patients with sickle cell disease (SCD). Since vitamin D deficiency and SCD share common manifestations including chronic pain, poor bone health and chronic systemic inflammation, it is reasonable to postulate that vitamin D deficiency may contribute to these complications. Thus, optimizing vitamin D nutrition represents an inexpensive strategy that may improve vitamin D status and health outcomes in SCD children. The working hypothesis is that administration of a single oral bolus of 300,000 IU of vitamin D3 to SCD children will result in the attainment of vitamin D sufficiency (25OHD levels >75 nmol/L) in 80% of participants after 3 months. The primary objectives are to assess feasibility, acceptability, and safety of the vitamin D3 bolus while secondary objectives are related to the mean change in serum 25OHD from baseline to 3 months post-bolus and its clinical impact. Seventy-two SCD children (5-17 years, SS and SC genotypes) will be randomized to one bolus of 300,000 IU of vitamin D3 or identical placebo. Blood will be collected at baseline and 3-month post-bolus to measure serum 25OHD and calculate the change from baseline at 3 months (efficacy outcomes). Other outcomes include urinary calcium/creatinine ratio and serum calcium (safety), questionnaires (acceptability and musculoskeletal pain) and parameters related to growth, haematology, inflammation and bone health (exploratory outcomes).

Inclusion Criteria:

• Children aged between 5 and 17 years old who are followed up at the SCD Clinic, CHU Sainte-Justine, Montreal, Canada.

Exclusion Criteria:

• Conditions or use of medications known to interfere with calcium or vitamin D absorption or metabolism
• Known hypercalcemia
• Conditions characterized by a hypersensitivity to vitamin D (e.g. granulomatous disorders)
• Patients clinically diagnosed with rickets or other conditions requiring vitamin D therapy
• History or presence of urolithiasis
• Anticipated difficult follow up
• Patients already enrolled in other investigational studies
• Patients who have recently been hospitalized for severe pain crisis or acute sickle complication in the past 2 weeks
• Patients with unresolved pain issues

The Applied Clinical Research Unit of Sainte-Justine UHC will generate the randomisation scheme. Group allocation codes will be held in a secure location with a restricted access by the Central pharmacy (Sainte-Justine UHC). All participants and research personnel, including the nurse, research trainee and research team will be blinded to group assignment.

The supplier Euro-Pharm will provide the placebo and vitamin D3 preparations in coded bottles. Pharmacy will prepare the 6-mL bolus in coded syringes following the randomisation scheme.