The Efficacy and the Safety of Vitamin D3 30,000 IU for Loading Dose Schedules
Condition: Vitamin D Deficiency
MeSH terms: Vitamin D Deficiency
Study type: Interventional
Phase: Phase 3

Summary: 
      Treatment: A: Slower Loading Group (SLD): 30.000 IU cholecalciferol once weekly for ten
      weeks, followed by 30.000 IU cholecalciferol every two weeks for four weeks.

      B: Moderate Loading Dose group (MLD): 30.000 IU cholecalciferol twice weekly for five weeks,
      followed by 30.000 IU cholecalciferol every two weeks for four weeks.

      Every patients will receive calcium-citrate supplementation if average daily calcium intake
      does not reach the recommended daily amount.

      Setting: two-arms, controlled, randomised, comparative open-label, multicentric clinical
      trial aimed to assess the comparative efficacy on 25(OH)D elevation and on safety of the two
      loading dose schedules of 30.000 IU Vitamin D3 oral tablets (administered as "Moderate
      Loading Dose"or "Slower Loading Dose") combined with an follow-up maintenance period of
      biweekly administration. The comparative assessment is based on the elevation of 25(OH)D
      levels due to treatment efficacy from baseline and by the end of the maintenance (biweekly
      30.000 IU) period for each treatment groups, and also the ratio of patients in target range
      (30-50 ng/ml) in order to evaluate the most beneficial "loading dose" schedule. Upon the
      serum 25(OH)D levels are exceeded the 55ng/ml limits by the end of the loading period the
      trial subjects should continue with the standard maintenance dose of vitamin D3 for the
      remaining four weeks of the study. The evaluation of the comparative safety will be done also
      by controlling the serum and the urinary calcium levels and the registration of adverse drug
      reaction.

      The primary objective is to assess the efficacy of the orally administered loading dose
      schedules of vitamin D3 in deficient patients. Efficacy is measured as the elevation of
      25(OH)D levels compared to baseline.

      Rationale: Oral vitamin D3 is the treatment of choice in vitamin D deficiency. The UK NOS
      guideline recommended where rapid correction of vitamin D deficiency is required, such as in
      patients with symptomatic disease or about to start treatment with a potent antiresorptive
      agent, the recommended treatment regimen is based on fixed loading doses followed by regular
      maintenance therapy. The loading dose regimen to provide a total of approximately 300,000 IU
      vitamin D, given either as separate weekly or daily doses over 6 to 10 weeks followed by a
      maintenance therapy comprising vitamin D in doses equivalent to 800-2000 IU daily in general
      or up to 4,000 IU daily), given either daily or intermittently at higher doses. (NOS
      guidelines 2014). Recent research on vitamin D and the widening range of therapeutic
      applications available for cholecalciferol, which can be classified as both a vitamin and a
      pro-hormone. Additionally, it was now realized that the Food and Nutrition Board's previously
      defined Upper Limit (UL) for safe intake at 2,000 IU/day was set far too low and that the
      physiologic requirement for vitamin D in adults may be as high as 5,000 IU/day, which is less
      than half of the >10,000 IU that can be produced endogenously with full-body sun exposure.

      In a recent study showed that the safety of doses over 2000 IU/day-4000 IU/day for 3 months
      resulting in a ~360,000 UI cumulative dose. According to the study results, for the majority
      of the patients the 4000 IU/day (360,000 UI cumulative dose) was needed to achieve a 25(OH)D
      serum concentration above 75nmol/L (30 ng/mL), which is otherwise set as the target value by
      Endocrine Society Clinical Practice Guideline (Holick 2011b).

      Another study (Verussio et al 2014) cited shows the safety and efficacy of 50.000 IU/week for
      8 weeks (400,000 UI cumulative dose for 8 weeks), followed by 25,000 IU twice a month which
      was more effective in raising the 25(OH)D level to the target range (of >30 ng/L) than 25,000
      IU twice a month (50,000 IU/ month). In the latter group only 40% of the patients reached the
      target 25(OH)D levels at 6 months, compared to the 72% in the first group. The study supports
      efficacy of dosing and safety of the treatment of vitamin D deficiency a 50,000 IU /week
      loading dose scheme with a 8 weeks cumulative dose of >400,000 UI.
    


Intervention name(s): Cholecalciferol
Intervention type(s): Drug
Intervention description(s): tablet containing 30.000IU cholecalciferol
Intervention MeSH terms: Cholecalciferol; Vitamin D
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: vitamin D deficiency; vitamin D loading dose