Investigating the Effects of Hydroxyvitamin D3 on Multiple Sclerosis

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

Official title:

Investigating the Effects of Hydroxyvitamin D3 Versus Vitamin D3 on Clinical, and Radiologic Progress and Th17/Tregs Balance in MS Patients: A Randomized, Clinical Trial- a Pilot Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05340985
• Other study ID #: 1400-3-233-56129
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: July 2022
• Est. completion date: December 2023

Study information

• Verified date: February 2022
• Source: Tehran University of Medical Sciences
• Contact: Zhila Maghbooli
• Phone: 00989121973516
• Email: zhilayas[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Investigating the effects of hydroxyvitamin D3 on clinical, radiologic and immunomodulatory markers in MS patients: A randomized, clinical trial- a pilot study

Description:

Vitamin D deficiency/insufficiency is a risk factor for developing MS and is linked to increased disease activity in those with established disease. Several clinical trials have already been conducted to consider the effect of vitamin D supplementation on clinical outcomes of the disease but the findings were inconsistent. This paradox may be explained by supplementation dose, trial duration and also an insufficient rise in serum 25-hydroxyvitamin D to be effective on immunomodulatory pathways and consequent clinical outcomes. Of note, it was revealed that MS patients have a lower rise in serum 25-hydroxyvitamin D [25(OH)D] levels compared with healthy controls (HCs), when given the same amount of oral cholecalciferol supplementation. Cholecalciferol is the main vitamin D supplement that was used in these trials. When vitamin D3 is ingested, it is incorporated into chylomicrons and enters the lymphatic system. The chylomicrons then enter into the bloodstream via the superior cava. Most of the vitamin D is incorporated into the body fat. Vitamin D3 in the circulation and the vitamin D3 that is slowly released from the body fat into the circulation is converted in the liver to 25(OH)D3, taking approximately 6-8 weeks to achieve a steady state concentration of 25(OH)D3. The more rapid increase in serum concentrations of 25(OH)D3, by treatment with calcifediol instead of cholecalciferol, may provide an advantage through rapid entry into its target innate and adaptive immune cells, resulting in the paracrine/autocrine production of 1α,25(OH)2D which interacts with the vitamin D receptor (VDR) to modulate immune function.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 54
• Est. completion date: December 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. MS type: relapsing-remitting MS (RRMS)

2. older than 18 year-old

3. Vitamin D deficiency/insufficiency (25(OH)D<30 ng/ml

Exclusion Criteria:

1. medications or disorders that would affect vitamin D metabolism

2. history of other chronic disorders

3. history of conditions that could lead to high serum calcium levels

4. pulse therapy in the last 3 months

5. history of attack in the last 3 months

6. using corticosteroid in the last 3 months

7. be pregnant

Related Conditions & MeSH terms

• Adult ALL
• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis
• Vitamin D3 Deficiency

Intervention

Dietary Supplement:
• 25(OH)D3
calcifediol
• vitamin D3
Cholecalciferol

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Tehran University of Medical Sciences	Boston University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of relapses	neurologic symptoms lasting more than 24 hours which occur at least 30 days after the onset of a preceding event	6 months (baseline and end of 6th month) in each intervention arm
Primary	disability	Change in expanded disability status scale (EDSS) according to Kurtzke 1983. The minimum is 0 (no disability) and maximum value is 10 (Death due to MS)- higher scores mean a worse outcome.	6 months (baseline and end of 6th month) in each intervention arm
Primary	Change in MRI parameters	new lesions on T2 weighted images, gadolinium enhancing lesions in T1-weighted images	6 months (baseline and end of 6th month) in each intervention arm
Primary	changing in brain parameters of Diffusion tensor imaging (DTI)	the integrity of white matter (WM) by analyzing WM microstructure through DTI	6 months (baseline and end of 6th month) in each intervention arm
Primary	changing in Cognition	Changing in cognitive functions by the Minimal Assessment of Cognitive Function in MS (MACFIMS) battery. The lower the score the more disfunction.; MACFIMS is consisting of 7 subtests including: the California Verbal Learning Test second edition (CVLT-II), with the range score: 0-80; the Paced Auditory Serial Addition Test (PASAT), with the range score: 0-16; the Symbol Digit Modalities Test (SDMT), with the range score: 0-110; the Brief Visuospatial Memory Test-Revised (BVMT-R), with the range score: 0-36; the Controlled Oral Word Association Test (COWAT), with the range score: 0-12; the Delis-Kaplan Executive Function System (DKEFS) sorting Test, with the range score: 0- undetermined; the Judgment of Line Orientation Test (JLO), with the range score: 0-30; The higher score in each subtest means the better cognitive function	6 months (baseline and end of 6th month) in each intervention arm
Primary	CD4+ T cell response	After six months, changing the balance of Th17 and Tregs subtypes of CD4+ T cells.; Detecting interleukin (IL) 17 -expressing T cells and Tregs expressing T cells by flow cytometry.	6 months (baseline and end of 6th month) in each intervention arm
Primary	Differential gene expression	After six months of 25-hydroxy vitamin D supplementation, the differentially expressed genes (DEGs) in peripheral blood mononuclear cells at the transcriptome level will be considered by RNA-seq	6 months (baseline and end of 6th month) in each intervention arm
Secondary	needing hospitalization	needing hospitalization due to remissions and exacerbations of the disease	6 months (baseline and end of 6th month) in each intervention arm
Secondary	changing in quality of life	changing in quality of life that determined by the Short Form Health Survey that contains 36-item (Sf36). The score is between 0-100.; The lower the score the more disability. The higher the score the less disability.	6 months (baseline and end of 6th month) in each intervention arm
Secondary	effective in rapidly raising circulating levels of 25(OH)D3	Serum levels of 25-hydroxy vitamin D (25(OH)D will be measured by High-performance liquid chromatography (HPLC)	6 months (baseline and end of 6th month) in each intervention arm
Secondary	changing in the circulating levels of interleukin 17 as a inflammatory marker	After six months of calcifediol/or cholecalciferol supplementation, measuring serum levels of IL-17 by enzyme-linked immunoassay (ELIZA) kit.	6 months (baseline and end of 6th month) in each intervention arm
Secondary	changing in the levels of interleukin 10 as anti- inflammatory marker	After six months of calcifediol/or cholecalciferol supplementation, measuring serum levels of IL-10 by ELIZA kit.	6 months (baseline and end of 6th month) in each intervention arm
Secondary	changing in the levels of Tumor Necrosis Factor alpha (TNF-a) as an inflammatory marker related the T-CD4 subsets	After six months of calcifediol/or cholecalciferol supplementation, measuring serum levels of TNF-a by ELIZA kit.	6 months (baseline and end of 6th month) in each intervention arm