Clinical trial NCT02063334: The Effect of a High-dose Oral Vitamin D3 Bolus on Serum 25(OH)D3 and Vitamin D Receptor Target Gene Expression
Official title: The Effect of a High-dose Oral Vitamin D3 Bolus on Serum 25-hydroxyvitamin D3 and Vitamin D Receptor Target Gene Expression (VitDbol)
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
randomized controlled trial
men
adults
Lead sponsor: University of Eastern Finland
Sponsor class: OTHER
First posted: 2014-02-14
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of the study is to investigate 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.

Detailed description: Serum 25-hydroxyvitamin D \[25(OH)D3\] 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 study (VitDmet, Clinicaltrials.gov NCT01479933) we showed that only half of the participants responded to the 5-month vitamin D3 supplementation of 40 µg/day or 80 µg/day as expected and that certain vitamin D receptor (VDR) target genes were suitable biomarkers for displaying the transcriptomic response of human tissues to vitamin D3 supplementation.

The purpose of the current study is to investigate whether a high-dose vitamin D3 oral bolus produces marked VDR target gene expression response and whether there is large inter-individual variation, as what was suggested with the 5-month lower-dose supplementation.

In the Trial 1, the subjects are randomized to receive either 2,000 micrograms (80 000 IU) of vitamin D3 (n=20) or placebo (n=10) in one day. Blood samples are collected for peripheral blood mononuclear cell isolation and serum 25(OH)D3 measurements at baseline and 24 h and 48 h and 30 days after the first dose. Blood samples are also collected for immunomarker analyses. In the Trial 2, the procedures of the Trial 1 are repeated in two subjects with known low and high serum 25(OH)D3 concentrations in order to investigate more specifically the impact of different starting levels of serum 25(OH)D3.

In February 2015, new subjects were recruited to enter the Trial 1 in order to increase the size of the study. All the new subjects received the 2,000 microgram bolus of vitamin D3, there were no new subjects in the placebo arm.

June 30, 2016. Change to protocol: There will be no Trial 2, but instead the blood samples obtained in the Trial 1 from up to six subjects will be used for the additional analyses. The subjects are selected based on the response to vitamin D supplementation in the Trial 1.

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 vitamin D.

Primary outcomes:
measure: Change from baseline in vitamin D target gene expression
timeFrame: 24 h, 48 h, and 30 days after the baseline
Secondary outcomes:
measure: Change from baseline in serum 25(OH)D
timeFrame: 24 h, 48 h, and 30 days after the baseline
Other outcomes:
measure: Change from baseline in immunomarkers
timeFrame: 24 h, 48 h, and 30 days after the baseline
measure: Change from baseline in glucose metabolism
timeFrame: 24 h, 48 h, and 30 days after the baseline
measure: Change from baseline in safety measurements
timeFrame: 48 h and 30 days after the baseline
Locations:
city: Kuopio
country: Finland
facility: University of Eastern Finland
Study officials:
affiliation: University of Eastern Finland
name: Jyrki K Virtanen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Seuter S, Virtanen JK, Nurmi T, Pihlajamaki J, Mursu J, Voutilainen S, Tuomainen TP, Neme A, Carlberg C. Molecular evaluation of vitamin D responsiveness of healthy young adults. J Steroid Biochem Mol Biol. 2017 Nov;174:314-321. doi: 10.1016/j.jsbmb.2016.06.003. Epub 2016 Jun 6.