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.

Inclusion Criteria:

- patients with sickle cell disease

- 3 to 20 years old

- pregnant females with sickle cell disease are eligible

Exclusion Criteria:

- no informed consent or assent

- unable or unwilling to comply with requirements of the clinical trial

- participation in another clinical trial

- history of hypercalcemia or diagnosis of any medical condition associated with
hypercalcemia, such as primary hyperparathyroidism, malignancy, familial hypocalciuric
hypercalcemia, William's syndrome and other rare causes

- therapy with thiazide diuretics or lithium carbonate

- known renal or liver disease

- known malabsorption syndrome and inflammatory bowel disease

- chronic use of corticosteroids, excluding inhaled steroids

- current use of anticonvulsants (phenytoin, phenobarbital, carbamazepine)

- current intake of vitamin D and calcium supplements

- initiation of hydroxyurea or iron chelation therapy within the past 3 months

- serum 25hydroxyvitamin D >60 ng/mL