Efficiency of Vitamin D3 and 25-hydroxyvitamin D3 on Transcriptomic Changes of Low Vitamin D Responders
Condition: Vitamin D Receptor Target Gene Expression; Serum 25(OH)D Concentration
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to investigate in vivo whether a high-dose vitamin D3 oral bolus
      (2000 micrograms) produces marked vitamin D receptor target gene expression response and
      whether there is large inter-individual variation. These effects are compared to in vitro
      treatment of peripheral blood mononuclear cells from these subjects with 25(OH)D.
    

Detailed description: 
      Serum 25-hydroxyvitamin D3 [25(OH)D3] is a well-established marker for vitamin D status of
      the human body. In addition to the general importance of vitamin D for bone health, low serum
      25(OH)D3 concentrations have been associated with increased risk of several health outcomes,
      such as autoimmune diseases, type 2 diabetes and cardiovascular complications. However, there
      is significant inter-individual variation in the average serum 25(OH)D3 concentrations and
      also in the response to supplementation with vitamin D. Genetic and epigenetic factors have
      been suggested to be responsible for a large part of the variation, but currently there is
      little information about the health effects of the variation.

      In our previous studies VitDmet (Clinicaltrials.gov NCT01479933) and VitDbol
      (Clinicaltrials.gov NCT02063334) we showed that the participants can be classified into high,
      mid and low responders to vitamin D and defined the new biomarker "vitamin D response index".
      Some 25% of the population seem to be low responders and are under higher risk to suffer from
      insufficient supplementation with vitamin D. The current study will focus on low vitamin D
      responders (among the 40 healthy individuals recruited in the study, 20-60 years old), i.e.
      it will use the same oral vitamin D3 bolus (2,000 µg, i.e. 80,000 IU in one day) as in our
      VitDbol study, in order to identify low vitamin D responders.

      By in vitro treatment of peripheral blood mononuclear cells (PBMCs) of low responders with
      25(OH)D3 for 24 h (in comparison to in vitro stimulations with 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3] and in vivo vitamin D3 supplementation of the same subjects) we will obtain
      samples that allow the transcriptome-wide investigation of changes in gene expression. The
      underlying hypothesis of this study is that a stimulation with 25(OH)D3 is more efficient
      than a treatment with vitamin D3, so that in future low vitamin D responders may be
      supplemented with 25(OH)D3 rather than with vitamin D3.
    

Intervention name(s): Vitamin D3
Intervention type(s): Dietary Supplement
Intervention description(s): In total 20 pills will be taken by the subjects, each containing 100 micrograms of vitamin D3, resulting in the total amount of 2000 micrograms of vitamin D3. Of the 20 pills, 10 will be taken in the morning with breakfast and 10 with lunch.
Other intervention name(s): cholecalciferol
Intervention MeSH terms: Vitamin D; Cholecalciferol
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: vitamin D3; cholecalciferol; calcidiol; 25-hydroxyvitamin D; gene expression; vitamin D receptor; adults; clinical trial