Defining Vitamin D Insufficiency in School Age Children: A Randomized Placebo Controlled Trial of Vitamin D3
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      The study objective is to characterize the threshold levels of serum 25-hydroxyvitamin D for
      the definition of vitamin D insufficiency in 8-14 year old African American and Caucasian
      children.

      We propose a 6 month randomized placebo controlled trial of vitamin D (vitamin D3 1000 IU/day
      vs. placebo) initiated during October through March (during fall and winter) in 8 to 14 year
      old African American and Caucasian children. The results of the trial will help establish the
      cutoff threshold value of serum 25(OH)D for defining vitamin D insufficiency in preadolescent
      and adolescent children. Safety of vitamin D supplementation will be assessed by measuring
      serum calcium at 0, 2 and 6 months and by monitoring for adverse events. Currently
      recommended adequate intake for vitamin D of 200 IU daily may not meet the body's daily needs
      for vitamin D. Therefore, it is likely that a higher level of daily vitamin D intake may be
      needed to meet the body's skeletal and non-skeletal demands for vitamin D. Determining the
      dietary required intake of vitamin D for the prevention of vitamin D insufficiency during
      childhood has immense public health potential for addressing health disparities and ensuring
      better bone health during adulthood. The primary outcome measure will be serum 25(OH)D and
      parathyroid hormone (PTH). The secondary outcome measures will include: markers of bone
      formation (serum P1NP) and bone resorption (serum CTX).We will also examine differences in
      serum 25(OH)D, PTH, and markers of bone turnover in African American vs. Caucasian children.
    

Detailed description: 
      Epidemiologic and clinical data document a high prevalence of vitamin D insufficiency among
      adults and adolescents in the US. Vitamin D insufficiency during childhood has the potential
      to impact the acquisition of peak bone mass. Vitamin D insufficiency is also associated with
      several non-skeletal disorders including cancer (prostate, breast, and colon), diabetes
      mellitus (type 1 and type 2), and multiple sclerosis. In our pilot study nearly 50% of 6 to
      10 year old African American children residing in Pittsburgh, Pennsylvania, were deemed
      vitamin D insufficient (serum 25-hydroxyvitamin D (25(OH)D): ≤ 20 ng/mL; Rajakumar K, et al.
      Clinical Pediatrics. 2005;44:683-692). To extend this field further, we are proposing a
      randomized placebo-controlled trial of vitamin D3 for establishing the serum
      25-hydroxyvitamin D (25(OH)D) cutoff threshold levels for defining vitamin D insufficiency
      during childhood and to document the safety and efficacy of treatment on the vitamin D status
      of the study cohort. A total of 168 (African American: 84, Caucasian: 84) 8 to 14 year old
      preadolescent and adolescent children will undergo a randomized-placebo controlled trial
      (RCT) of vitamin D3 1000 IU daily vs. placebo for 6 months initiated during fall and winter
      (October through March). Safety of vitamin D supplementation will be assessed by measuring
      serum calcium at 0, 2 and 6 months and by monitoring for adverse events. We will also examine
      the differences in serum 25(OH)D, PTH, and markers of bone turnover in African American vs.
      Caucasian children. The primary outcome measure will be serum 25(OH)D and PTH. The secondary
      outcome measures will include: markers of bone formation: serum osteocalcin (OC) and bone
      resorption: serum C-terminal cross-linking telopeptide of type 1 collagen (serum CTX).
      Additional outcomes will include: dietary intake of vitamin D and calcium, skin color
      (Fitzpatrick Sunreactive Skin Type and Melanin Index), sun exposure, and body mass index.
      Vitamin D deficiency will be defined as serum 25-hydroxyvitamin D concentrations <20 ng/mL.
      Public health importance of childhood vitamin D insufficiency is linked to the impact of
      vitamin D status on the acquisition of peak bone mass. Reduced peak bone mass can predispose
      to premature onset of osteoporosis and increase the risk for osteoporosis related fragility
      fractures. Achieving and maintaining vitamin D sufficiency during childhood can positively
      impact the skeletal health of children and reduce their "osteoporosis" burden during
      adulthood, and modify their risk for the non-skeletal disorders associated with chronic
      vitamin D insufficiency. Paucity of data regarding threshold levels of serum 25(OH)D
      associated with vitamin D insufficiency status among school age children and the likelihood
      that the serum 25(OH)D threshold levels for vitamin D sufficiency could be different among
      African American and Caucasian children makes it compelling for this issue to be explored.
      Based on expert opinion and supportive data in the medical literature, we feel that the
      currently recommended adequate intake for vitamin D for pre- and adolescent children (200 IU
      daily) is woefully inadequate to meet the daily needs for vitamin D. Therefore, it is likely
      that a higher level of daily vitamin D intake may be needed to meet the body's skeletal and
      non-skeletal demands for vitamin D. This study will determine the serum 25(OH)D cutoff for
      the definition of vitamin D insufficiency and document the safety and efficacy of treatment
      on vitamin D status.
    

Intervention name(s): Vitamin D3 1000 IU; Placebo Tablet
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Vitamin D3 1000 IU Tablet once daily for 6 months; Placebo Tablet once daily for 6 months
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: Vitamin D Deficiency; Vitamin D Insufficiency; Child; Adolescent; African American; Caucasian; Definition; Preadolescent