The Effect of a High-dose Oral Vitamin D3 Bolus on Serum 25(OH)D3 and Vitamin D Receptor Target Gene Expression

Serum 25(OH)D Concentration Clinical Trial

— VitDbol  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02063334
• Other study ID #: VitDbol
• Status: Completed
• Phase: Phase 1
• First received: February 4, 2014
• Last updated: July 28, 2016
• Start date: February 2014
• Est. completion date: June 2015

Study information

• Verified date: June 2016
• Source: University of Eastern Finland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Finland: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Serum 25(OH)D Concentration
• Vitamin D Receptor Target Gene Expression

Intervention

Dietary Supplement:
• Vitamin D3
In total 25 pills will be taken by the subjects, each containing 80 micrograms of vitamin D3 or placebo. Of the 25 pills, 13 will be taken in the morning with breakfast and 12 with lunch.
• Placebo

Locations

Country	Name	City	State
Finland	University of Eastern Finland	Kuopio

Sponsors (1)

Lead Sponsor	Collaborator
University of Eastern Finland

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from baseline in immunomarkers	Effect of 2000 microgram Vitamin D3 dose or placebo on immune system and inflammatory responses, such as hs-CRP, IL-6, TNF-alfa and IL-1RA.	24 h, 48 h, and 30 days after the baseline	Yes
Other	Change from baseline in glucose metabolism	Effect of 2000 microgram vitamin D3 dose or placebo on glucose metabolism responses, i.e. blood glucose and insulin	24 h, 48 h, and 30 days after the baseline	Yes
Other	Change from baseline in safety measurements	Serum calcium, alanine transaminase (ALAT), gamma-glutamyl transferase (GGT) and creatinine	48 h and 30 days after the baseline	Yes
Primary	Change from baseline in vitamin D target gene expression	Effect of 2000 microgram vitamin D3 dose or placebo on the expression of vitamin D receptor target genes	24 h, 48 h, and 30 days after the baseline	No
Secondary	Change from baseline in serum 25(OH)D	Effect of 2000 microgram vitamin D3 dose or placebo on serum 25(OH)D3 concentrations	24 h, 48 h, and 30 days after the baseline	Yes