Clinical trial NCT03537027: Efficiency of Vitamin D3 and 25-hydroxyvitamin D3 on Transcriptomic Changes of Low Vitamin D Responders
Official title: Comparing the Efficiency of Vitamin D3 and 25-hydroxyvitamin D3 Treatment on Changes of the Transcriptome of Low Vitamin D Responders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Vitamin D Receptor Target Gene Expression
Serum 25(OH)D Concentration
Keywords: vitamin D3
cholecalciferol
calcidiol
25-hydroxyvitamin D
gene expression
vitamin D receptor
adults
clinical trial
Lead sponsor: University of Eastern Finland
Sponsor class: OTHER
Collaborators: name: DSM Nutritional Products, Inc.
First posted: 2018-05-25
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Non-smoking
* BMI 20-25 kg/m2.

Exclusion Criteria:

* History of kidney stones, renal failure or dialysis, hypercalcemia, hypo- or hyperparathyroidism, severe liver disease (cirrhosis), or sarcoidosis or other granulomatous diseases, such as active chronic tuberculosis or Wegener's granulomatosis.
* Continuous use of anti-inflammatory medicines.
* Regular use of supplements containing over 20 micrograms of vitamin D.

Primary outcomes:
measure: In vivo change from baseline in vitamin D target gene expression in the subjects
timeFrame: 24 hours after the baseline
measure: In vitro change from baseline in vitamin D target gene expression in peripheral blood mononuclear cells
timeFrame: 24 hours after the baseline
Secondary outcomes:
measure: In vivo change from baseline in serum 25(OH)D concentration
timeFrame: 24 hours after the baseline
measure: In vivo change from baseline in serum calcium concentration (safety and tolerability)
timeFrame: 24 hours after the baseline
measure: In vivo change from baseline in serum alanine transaminase concentration (safety and tolerability)
timeFrame: 24 hours after the baseline
measure: In vivo change from baseline in serum gamma-glutamyl transferase concentration (safety and tolerability)
timeFrame: 24 hours after the baseline
measure: In vivo change from baseline in serum creatinine concentration (safety and tolerability)
timeFrame: 24 hours after the baseline
Other outcomes:
Locations:
city: Kuopio
country: Finland
facility: University of Eastern Finland
Study officials:
affiliation: University of Eastern Finland
name: Carsten Carlberg, PhD
role: PRINCIPAL_INVESTIGATOR
References: