Efficiency of Vitamin D3 and 25-hydroxyvitamin D3 on Transcriptomic Changes of Low Vitamin D Responders (VitDHiD)

Comparing the Efficiency of Vitamin D3 and 25-hydroxyvitamin D3 Treatment on Changes of the Transcriptome of Low Vitamin D Responders

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.

Study Overview

• Status: Completed
• Conditions: Vitamin D Receptor Target Gene Expression; Serum 25(OH)D Concentration
• Intervention / Treatment: Dietary supplement: Vitamin D3

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Finland
  • Kuopio, Finland, 70211
    • University of Eastern Finland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin D3; 2000 micrograms of vitamin D3 in two doses during one day	Dietary supplement: Vitamin D3; 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 Names: cholecalciferol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In vivo change from baseline in vitamin D target gene expression in the subjects	Effect of 2000 microgram vitamin D3 dose on the expression of vitamin D receptor target genes	24 hours after the baseline
In vitro change from baseline in vitamin D target gene expression in peripheral blood mononuclear cells	Effects of treatment of cells for 24 h with 100 nM of 25(OH)D3, 1 nM of 1,25(OH)2D3 or vehicle (solvent) on the expression of vitamin D receptor target genes	24 hours after the baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In vivo change from baseline in serum 25(OH)D concentration	Effect of 2000 microgram vitamin D3 dose on serum 25(OH)D3 concentrations	24 hours after the baseline
In vivo change from baseline in serum calcium concentration (safety and tolerability)	Effect of 2000 microgram vitamin D3 dose on in vivo changes in serum calcium concentrations	24 hours after the baseline
In vivo change from baseline in serum alanine transaminase concentration (safety and tolerability)	Effect of 2000 microgram vitamin D3 dose on in vivo changes in serum alanine transaminase (ALAT) concentrations	24 hours after the baseline
In vivo change from baseline in serum gamma-glutamyl transferase concentration (safety and tolerability)	Effect of 2000 microgram vitamin D3 dose on in vivo changes in serum gamma-glutamyl transferase (GGT) concentrations	24 hours after the baseline
In vivo change from baseline in serum creatinine concentration (safety and tolerability)	Effect of 2000 microgram vitamin D3 dose on in vivo changes in serum creatinine concentrations	24 hours after the baseline

Collaborators and Investigators

• Sponsor: University of Eastern Finland
• Collaborators: DSM Nutritional Products, Inc.
• Investigators: Principal Investigator: Carsten Carlberg, PhD, University of Eastern Finland

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2018
• Primary Completion (Actual): May 31, 2018
• Study Completion (Actual): May 31, 2018

Study Registration Dates

• First Submitted: April 26, 2018
• First Submitted That Met QC Criteria: May 14, 2018
• First Posted (Actual): May 25, 2018

Study Record Updates

• Last Update Posted (Actual): October 12, 2018
• Last Update Submitted That Met QC Criteria: October 11, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: clinical trial; 25-hydroxyvitamin D; vitamin D3; adults; cholecalciferol; gene expression; calcidiol; vitamin D receptor
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: VitDHiD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No