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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
Tehran University of Medical Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Multiple Sclerosis, Relapsing-Remitting

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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

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

    First Posted
    March 2, 2022
    Last Updated
    April 16, 2022
    Sponsor
    Tehran University of Medical Sciences
    Collaborators
    Boston University
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    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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