Effect of Single High Dose of Cholecalciferol on Serum Metabolites of Vitamin D

• Sponsor: Department of Endocrinology, Centre of Postgraduate Medical Education (Other)
• Overall Status: Completed
• CT.gov ID: NCT05591170
• Collaborator: (none)
• Enrollment: 58
• Location: 1
• Arms: 2
• Actual Duration (Months): 5
• Patients Per Site Per Month: 11.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Vitamin D Deficiency	Drug: Cholecalciferol 120 000 IU	Phase 4

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 our study we would like 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. We would like also to 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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: The Effect of Single High Dose of Vitamin D on Serum Levels of Its Metabolites
• Actual Study Start Date: Apr 1, 2021
• Actual Primary Completion Date: Aug 31, 2021
• Actual Study Completion Date: Aug 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Study Group Participants received single, high, oral dose of vitamin D3 (120,000 IU), 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 (measured by LC-MS/MS) at baseline, 3 days and 7 days after bolus dose were measured. The percentage of fat tissue was determined using Dual-Energy X-Ray Absorptiometry (DXA).	Drug: Cholecalciferol 120 000 IU; single, oral administration of high dose of vitamin D; Other Names: Solderol
No Intervention: Control Group 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 (measured by LC-MS/MS) were measured at baseline, 3 days and 7 days after. The percentage of fat tissue was determined using Dual-Energy X-Ray Absorptiometry (DXA).

Outcome Measures

Primary Outcome Measures

1. Changes of serum vitamin D metabolites after the administration of 120 000 IU cholecalciferol compared to control group. [Measurements at baseline, 3 days and 7 days after.]

   Changes of 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 the intervention, compared to control group.

Secondary Outcome Measures

1. Influence of percentage of fat tissue on serum concentration of metabolites of vitamin D and their changes after bolus dose. [Dual-Energy X-Ray Absorptiometry (DXA) at baseline, measurements of vitamin D metabolites at baseline, 3 days and 7 days after.]

   Influence of percentage of fat tissue on serum 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, 3-epi-25(OH)D3, 1,25(OH)2D3 and their changes at baseline, 3 days and 7 days after the intervention, compared to control group.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Endocrinology, Centre of Postgraduate Medical Education	Warszawa		Poland	01-813

Sponsors and Collaborators

• Department of Endocrinology, Centre of Postgraduate Medical Education

Investigators

• Study Chair: Wojciech Zgliczyński, Prof., Department of Endocrinology, Centre of Postgraduate Medical Education

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• Responsible Party: Dorota Lesczyńska, MD, Department of Endocrinology, Centre of Postgraduate Medical Education
• ClinicalTrials.gov Identifier: NCT05591170
• Other Study ID Numbers: 042021082021
• First Posted: Oct 24, 2022
• Last Update Posted: Oct 24, 2022
• Last Verified: Oct 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Dorota Lesczyńska, MD, Department of Endocrinology, Centre of Postgraduate Medical Education: vitamin D; 25(OH)D3; 25(OH)D2; 3-epi-25(OH)D3; 24,25(OH)2D3; 1,25(OH)2D3
• Additional relevant MeSH terms: Vitamin D Deficiency; Cholecalciferol; Vitamin D

Study Results

No Results Posted as of Oct 24, 2022