Study of Vitamin D in Children With Sickle Cell Disease

Sickle cell disease is a genetic red blood cell disorder that affects an estimated 89,000 Americans, predominantly those of African ancestry. The leading causes of morbidity and of death in sickle cell disease are respiratory complications, particularly a life-threatening lung disease unique to sickle cell disease called the "acute chest syndrome". An infectious trigger and a pro-inflammatory state appear to be critical mechanisms of the respiratory problems in sickling disorders. Emerging evidence that vitamin D has antimicrobial and anti-inflammatory functions in the respiratory tract, and the recognition of widespread vitamin D insufficiency in sickle cell children provide a compelling new rationale for vitamin D supplementation in sickle cell disease.

This will be an open label, single arm study to assess the efficacy and safety of oral vitamin D3 100,000 IU administered monthly for six months in children and adolescents with sickle cell disease. Twelve pediatric patients with sickle cell disease, 3-20 years old, will be recruited. The primary outcome measure (efficacy and safety) will be serum 25-hydroxyvitamin D concentration. Other safety measures will include serum calcium and urinary calcium and creatinine. Serial measurements of serum 25-hydroxyvitamin D, serum chemistries, and urinary calcium and creatinine will be performed at baseline entry, monthly for six months during treatment with vitamin D3, and at study exit. Other measures relevant to our planned Phase 2 clinical trial, including markers of bone turnover, immune function, and inflammation, will also be obtained at baseline, midpoint and exit. Recruitment and enrollment of subjects is expected to be for 3 months; study assessments will be for 7 months (1 month screening and 6 months treatment); and, the remaining 2 months will be devoted to data collation and analysis.

Study Procedures

Screening: After signing written informed consent by a parent or legal guardian (and assent, if applicable) or patient, eligible participants will undergo a screening examination including a standardized history and physical examination.

A venous blood sample will be obtained for baseline screening measures including serum 25-hydroxyvitamin D, serum chemistries, and urine calcium and creatinine. Within one month, eligible participants who do not have any of the exclusion criteria will return for enrollment in the pilot study.

Intervention: Participants will be seen monthly for administration of oral vitamin D3 100,000 IU under the direct observation by the Clinical Research Nurse. History and examination will be performed to capture symptoms and signs of adverse events. Questionnaires to collect data on vitamin D and calcium dietary intake and respiratory events will be administered. Venous blood and urine samples for study assessments (serum 25-hydroxyvitamin D, serum albumin, calcium and phosphate, urine calcium and creatinine) will be obtained at each visit prior to administration of study drug.