Investigating the Effects of Hydroxyvitamin D3 on Multiple Sclerosis

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis, Relapsing-Remitting; Vitamin D3 Deficiency; Adult ALL
• Intervention / Treatment: Dietary supplement: 25(OH)D3; Dietary supplement: vitamin D3

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Zhila Maghbooli; Phone Number: 00989121973516; Email: zhilayas@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 25(OH)D3 (Calcifediol); 50 micrograms per day 25(OH)D3 or vitamin D hydroxylated for 24 weeks	Dietary supplement: 25(OH)D3; calcifediol; Other Names: vitamin D analog
Experimental: Cholecalciferol; 50 micrograms (2000IU) per day Cholecalciferol for 24 Weeks	Dietary supplement: vitamin D3; Cholecalciferol; Other Names: activated 7-dehydrocholesterol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
needing hospitalization	needing hospitalization due to remissions and exacerbations of the disease	6 months (baseline and end of 6th month) in each intervention arm
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Collaborators: Boston University
• Investigators: Principal Investigator: Michael F Holick, PhD,MD, Boston University; Study Chair: Mohamadali Sahraian, MD, Multiple Sclerosis Research Center, Tehran University of Medical Sciences; Principal Investigator: Zhila Maghbooli, PhD, Multiple Sclerosis Research Center, Tehran University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2022
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: March 2, 2022
• First Submitted That Met QC Criteria: April 16, 2022
• First Posted (Actual): April 22, 2022

Study Record Updates

• Last Update Posted (Actual): April 22, 2022
• Last Update Submitted That Met QC Criteria: April 16, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Provitamins; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols; Calcifediol; Dehydrocholesterols; 7-dehydrocholesterol
• Other Study ID Numbers: 1400-3-233-56129

Drug and device information, study documents

• 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