Study of Vitamin D in Children With Sickle Cell Disease
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This pilot study aims to answer the question whether monthly oral vitamin D3 supplementation,
      100,000 IU, will be safe and effective in raising serum 25-hydroxyvitamin D (form of vitamin
      D measured in the blood) to levels considered sufficient (30 ng/mL) but well below the
      threshold for toxicity (150 ng/mL) in children with sickle cell disease. Information from
      this study will be crucial before we perform a larger clinical trial to determine the effects
      of vitamin D in reducing respiratory complications in patients with sickle cell disease.
    

Detailed description: 
      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.
    

Intervention name(s): Vitamin D3
Intervention type(s): Drug
Intervention description(s): Oral vitamin D3 100,000 IU administered monthly for six months in children and adolescents with sickle cell disease
Other intervention name(s): Vitamin D
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: sickle cell disease; children; vitamin D; safety