Clinical trial NCT05591170: Effect of Single High Dose of Cholecalciferol on Serum Metabolites of Vitamin D
Official title: The Effect of Single High Dose of Vitamin D on Serum Levels of Its Metabolites
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Vitamin D Deficiency
Keywords: vitamin D
25(OH)D3
25(OH)D2
3-epi-25(OH)D3
24,25(OH)2D3
1,25(OH)2D3
Lead sponsor: Department of Endocrinology, Centre of Postgraduate Medical Education
Sponsor class: OTHER
First posted: 2022-10-24
Enrollment: 58
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The aim of this interventional study is to assess the effect of the single high dose of vitamin D on its serum metabolites in elderly.

The main questions it attempts to answer is:

1. what is the effect of a single, high, oral dose of vitamin D3 (120,000 IU) on serum 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, 3-epi-25(OH)D3, 1,25(OH)2D3, 24,25(OH)2D3/25(OH)D3 ratio, and 25(OH)D3/3-epi-25(OH)D3 ratio concentration at baseline, 3 days and 7 days after administration, compared to control group.
2. what is the influence of percentage of fat tissue on serum metabolites of vitamin D and their changes after bolus dose, compared to control group.

Detailed description: Vitamin D belongs to dietary micronutriens and it is known for pleiotropic actions, going far beyond its classical function of maintenance of calcium/phosphorous homeostasis. The extra-skeletal effects of vitamin D include the role in cellular proliferation, differentiation, and immune modulation. Therefore, vitamin D has become the subject of numerous studies in relation to its potential protective effect in pathophysiology of diabetes, cardiovascular diseases, autoimmune diseases, infections and cancer.

The most common form of vitamin D is 25(OH)D3 - it can be obtained by photochemical reaction in the skin and through diet via animal-based food. 25(OH)D2 may be found in some plant-based food and has lower affinity to vitamin D binding protein, therefore it has a shorter half-life in the blood. In many countries, due to insufficient skin synthesis, vitamin D has to be acquired through fortified food and supplements in different dosing schedules (e.g. once daily, once weekly). Higher doses of vitamin D taken less frequently may significantly improve patients' adherence to recommended treatment regimens. However, there are arising questions about the efficacy and safety of such interventions. 1,25(OH)2D3 is the product of 1-hydroxylation of 25(OH)D3 in kidneys and it is the active form of vitamin D with a short half-life in the blood, while 24,25(OH)2D3 is the product of the reaction of 24-hydroxylase and it is considered inactive. The measurement of serum levels of both metabolites may contribute to better understanding the mechanisms protecting against too high increase of active forms of vitamin D.

In the study, the investigators aim to establish the changes of serum vitamin D metabolites (namely 25OHD, 25(OH)D3, 24,25(OH)2D3, 25(OH)D2, 3-epi-25(OH)D3 and 1,25(OH)2D3) and chosen ratios after oral administration of 120 000 IU of vitamin D 3 days and 7 days after the intervention in hospitalized elderly patients. The investigators also address a question if the change of serum vitamin D metabolites after single high dose of vitamin D3 is dependent on the body fat percentage and severity of vitamin D deficiency. Quantitative analyses were performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS).

Eligibility criteria: Inclusion Criteria:

* written, informed consent,
* age ≥ 60 years-old,
* admission to the hospital due to emergency reasons.

Exclusion Criteria:

* hypercalcemia,
* nephrolithiasis,
* kidney insufficiency,
* documented vitamin D3 metabolism disorders such as sarcoidosis, parathyroid disease or genetic defects,
* vitamin D3 supplementation within 6 months prior to the hospitalisation.

Primary outcomes:
measure: Changes of serum vitamin D metabolites after the administration of 120 000 IU cholecalciferol compared to control group.
timeFrame: Measurements at baseline, 3 days and 7 days after.
Secondary outcomes:
measure: Influence of percentage of fat tissue on serum concentration of metabolites of vitamin D and their changes after bolus dose.
timeFrame: Dual-Energy X-Ray Absorptiometry (DXA) at baseline, measurements of vitamin D metabolites at baseline, 3 days and 7 days after.
Other outcomes:
Locations:
city: Warszawa
country: Poland
facility: Department of Endocrinology, Centre of Postgraduate Medical Education
Study officials:
affiliation: Department of Endocrinology, Centre of Postgraduate Medical Education
name: Wojciech Zgliczyński, Prof.
role: STUDY_CHAIR
References:
citation: Ilahi M, Armas LA, Heaney RP. Pharmacokinetics of a single, large dose of cholecalciferol. Am J Clin Nutr. 2008 Mar;87(3):688-91. doi: 10.1093/ajcn/87.3.688.
citation: Saleh L, Tang J, Gawinecka J, Boesch L, Fraser WD, von Eckardstein A, Nowak A. Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in adults with vitamin D insufficiency. Clin Chem Lab Med. 2017 Oct 26;55(12):1912-1921. doi: 10.1515/cclm-2016-1129.