Investigating the Effects of Hydroxyvitamin D3 on Multiple Sclerosis

April 16, 2022 updated by: Tehran University of Medical Sciences

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

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
54

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of relapses
Time Frame: 6 months (baseline and end of 6th month) in each intervention arm
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
Time Frame: 6 months (baseline and end of 6th month) in each intervention arm
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
Time Frame: 6 months (baseline and end of 6th month) in each intervention arm
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)
Time Frame: 6 months (baseline and end of 6th month) in each intervention arm
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
Time Frame: 6 months (baseline and end of 6th month) in each intervention arm

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:

  1. the California Verbal Learning Test second edition (CVLT-II), with the range score: 0-80
  2. the Paced Auditory Serial Addition Test (PASAT), with the range score: 0-16
  3. the Symbol Digit Modalities Test (SDMT), with the range score: 0-110
  4. the Brief Visuospatial Memory Test-Revised (BVMT-R), with the range score: 0-36
  5. the Controlled Oral Word Association Test (COWAT), with the range score: 0-12
  6. the Delis-Kaplan Executive Function System (DKEFS) sorting Test, with the range score: 0- undetermined
  7. 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
Time Frame: 6 months (baseline and end of 6th month) in each intervention arm

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
Time Frame: 6 months (baseline and end of 6th month) in each intervention arm
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
needing hospitalization
Time Frame: 6 months (baseline and end of 6th month) in each intervention arm
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
Time Frame: 6 months (baseline and end of 6th month) in each intervention arm

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
Time Frame: 6 months (baseline and end of 6th month) in each intervention arm
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
Time Frame: 6 months (baseline and end of 6th month) in each intervention arm
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
Time Frame: 6 months (baseline and end of 6th month) in each intervention arm
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
Time Frame: 6 months (baseline and end of 6th month) in each intervention arm
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tehran University of Medical Sciences

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Boston University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2022

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 2, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 16, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 22, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 22, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 16, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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