Investigating the Effects of Hydroxyvitamin D3 on Multiple Sclerosis
Primary Purpose
Multiple Sclerosis, Relapsing-Remitting, Adult ALL, Vitamin D3 Deficiency
Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
25(OH)D3
vitamin D3
Sponsored by
About this trial
This is an interventional basic science trial for Multiple Sclerosis, Relapsing-Remitting
Eligibility Criteria
Inclusion Criteria:
- MS type: relapsing-remitting MS (RRMS)
- older than 18 year-old
- Vitamin D deficiency/insufficiency (25(OH)D<30 ng/ml
Exclusion Criteria:
- medications or disorders that would affect vitamin D metabolism
- history of other chronic disorders
- history of conditions that could lead to high serum calcium levels
- pulse therapy in the last 3 months
- history of attack in the last 3 months
- using corticosteroid in the last 3 months
- be pregnant
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
25(OH)D3 (Calcifediol)
Cholecalciferol
Arm Description
50 micrograms per day 25(OH)D3 or vitamin D hydroxylated for 24 weeks
50 micrograms (2000IU) per day Cholecalciferol for 24 Weeks
Outcomes
Primary Outcome Measures
Number of relapses
neurologic symptoms lasting more than 24 hours which occur at least 30 days after the onset of a preceding event
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.
Change in MRI parameters
new lesions on T2 weighted images, gadolinium enhancing lesions in T1-weighted images
changing in brain parameters of Diffusion tensor imaging (DTI)
the integrity of white matter (WM) by analyzing WM microstructure through DTI
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
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.
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
Secondary Outcome Measures
needing hospitalization
needing hospitalization due to remissions and exacerbations of the disease
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.
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)
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.
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.
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.
Full Information
NCT ID
NCT05340985
First Posted
March 2, 2022
Last Updated
April 16, 2022
Sponsor
Tehran University of Medical Sciences
Collaborators
Boston University
1. Study Identification
Unique Protocol Identification Number
NCT05340985
Brief Title
Investigating the Effects of Hydroxyvitamin D3 on Multiple Sclerosis
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 2022 (Anticipated)
Primary Completion Date
June 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tehran University of Medical Sciences
Collaborators
Boston University
4. Oversight
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
5. Study Description
Brief Summary
Investigating the effects of hydroxyvitamin D3 on clinical, radiologic and immunomodulatory markers in MS patients: A randomized, clinical trial- a pilot study
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Relapsing-Remitting, Adult ALL, Vitamin D3 Deficiency
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
This is a randomized clinical trial with a parallel group and allocation 1:1.
Masking
Outcomes Assessor
Masking Description
All participants at the MS clinic will be blinded to trial intervention allocation. The main outcomes will be evaluated by neurologists.
Investigator is also blind; two type of vitamin D; 25(OH)D3 and cholecalciferol capsules with similar shape and color.
Allocation
Randomized
Enrollment
54 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
25(OH)D3 (Calcifediol)
Arm Type
Experimental
Arm Description
50 micrograms per day 25(OH)D3 or vitamin D hydroxylated for 24 weeks
Arm Title
Cholecalciferol
Arm Type
Experimental
Arm Description
50 micrograms (2000IU) per day Cholecalciferol for 24 Weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
25(OH)D3
Other Intervention Name(s)
vitamin D analog
Intervention Description
calcifediol
Intervention Type
Dietary Supplement
Intervention Name(s)
vitamin D3
Other Intervention Name(s)
activated 7-dehydrocholesterol
Intervention Description
Cholecalciferol
Primary Outcome Measure Information:
Title
Number of relapses
Description
neurologic symptoms lasting more than 24 hours which occur at least 30 days after the onset of a preceding event
Time Frame
6 months (baseline and end of 6th month) in each intervention arm
Title
disability
Description
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.
Time Frame
6 months (baseline and end of 6th month) in each intervention arm
Title
Change in MRI parameters
Description
new lesions on T2 weighted images, gadolinium enhancing lesions in T1-weighted images
Time Frame
6 months (baseline and end of 6th month) in each intervention arm
Title
changing in brain parameters of Diffusion tensor imaging (DTI)
Description
the integrity of white matter (WM) by analyzing WM microstructure through DTI
Time Frame
6 months (baseline and end of 6th month) in each intervention arm
Title
changing in Cognition
Description
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
Time Frame
6 months (baseline and end of 6th month) in each intervention arm
Title
CD4+ T cell response
Description
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.
Time Frame
6 months (baseline and end of 6th month) in each intervention arm
Title
Differential gene expression
Description
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
Time Frame
6 months (baseline and end of 6th month) in each intervention arm
Secondary Outcome Measure Information:
Title
needing hospitalization
Description
needing hospitalization due to remissions and exacerbations of the disease
Time Frame
6 months (baseline and end of 6th month) in each intervention arm
Title
changing in quality of life
Description
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.
Time Frame
6 months (baseline and end of 6th month) in each intervention arm
Title
effective in rapidly raising circulating levels of 25(OH)D3
Description
Serum levels of 25-hydroxy vitamin D (25(OH)D will be measured by High-performance liquid chromatography (HPLC)
Time Frame
6 months (baseline and end of 6th month) in each intervention arm
Title
changing in the circulating levels of interleukin 17 as a inflammatory marker
Description
After six months of calcifediol/or cholecalciferol supplementation, measuring serum levels of IL-17 by enzyme-linked immunoassay (ELIZA) kit.
Time Frame
6 months (baseline and end of 6th month) in each intervention arm
Title
changing in the levels of interleukin 10 as anti- inflammatory marker
Description
After six months of calcifediol/or cholecalciferol supplementation, measuring serum levels of IL-10 by ELIZA kit.
Time Frame
6 months (baseline and end of 6th month) in each intervention arm
Title
changing in the levels of Tumor Necrosis Factor alpha (TNF-a) as an inflammatory marker related the T-CD4 subsets
Description
After six months of calcifediol/or cholecalciferol supplementation, measuring serum levels of TNF-a by ELIZA kit.
Time Frame
6 months (baseline and end of 6th month) in each intervention arm
10. Eligibility
Sex
All
Gender Based
Yes
Gender Eligibility Description
based on ID
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
MS type: relapsing-remitting MS (RRMS)
older than 18 year-old
Vitamin D deficiency/insufficiency (25(OH)D<30 ng/ml
Exclusion Criteria:
medications or disorders that would affect vitamin D metabolism
history of other chronic disorders
history of conditions that could lead to high serum calcium levels
pulse therapy in the last 3 months
history of attack in the last 3 months
using corticosteroid in the last 3 months
be pregnant
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhila Maghbooli
Phone
00989121973516
Email
zhilayas@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mohamadali Sahraian, MD
Organizational Affiliation
Multiple Sclerosis Research Center, Tehran University of Medical Sciences
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Zhila Maghbooli, PhD
Organizational Affiliation
Multiple Sclerosis Research Center, Tehran University of Medical Sciences
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael F Holick, PhD,MD
Organizational Affiliation
Boston University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Investigating the Effects of Hydroxyvitamin D3 on Multiple Sclerosis
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