Multiple Sclerosis, Relapsing-RemittingPhase 4NCT05340985
Investigating the Effects of Hydroxyvitamin D3 on Multiple Sclerosis
A Phase 4 study testing 25(OH)D3 and vitamin D3 in people with Multiple Sclerosis, Relapsing-Remitting and Adult ALL, run by Tehran University of Medical Sciences.
Trial summary
Investigating the effects of hydroxyvitamin D3 on clinical, radiologic and immunomodulatory markers in MS patients: A randomized, clinical trial- a pilot study Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting, Adult ALL, Vitamin D3 Deficiency
- What is being tested?
- 25(OH)D3 and vitamin D3
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- No sites listed yet
- Study dates
- Jul 2022to Dec 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- MS type: relapsing-remitting MS (RRMS)
- older than 18 year-old
- Vitamin D deficiency/insufficiency (25(OH)D<30 ng/ml
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet.
About this study
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
Investigating the effects of hydroxyvitamin D3 on clinical, radiologic and immunomodulatory markers in MS patients: A randomized, clinical trial- a pilot study
Read the 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.
- Being tested
- 25(OH)D3, vitamin D3
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
25(OH)D3Dietary supplement
Also called vitamin D analog
calcifediol
vitamin D3Dietary supplement
Also called activated 7-dehydrocholesterol
Cholecalciferol
| Study group | Role | What they receive |
|---|---|---|
| 25(OH)D3 (Calcifediol) | Experimental | 50 micrograms per day 25(OH)D3 or vitamin D hydroxylated for 24 weeks Receives: Dietary Supplement: 25(OH)D3 |
| Cholecalciferol | Experimental | 50 micrograms (2000IU) per day Cholecalciferol for 24 Weeks Receives: Dietary Supplement: vitamin D3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of relapses
neurologic symptoms lasting more than 24 hours which occur at least 30 days after the onset of a preceding event
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 6 months (baseline and end of 6th month) in each intervention arm
Secondary outcomes (6)
needing hospitalization
needing hospitalization due to remissions and exacerbations of the disease
Measured: 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.
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 6 months (baseline and end of 6th month) in each intervention arm
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2022
- Study startJul 2022 (estimated)
- Primary completionJun 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized clinical trial with a parallel group and allocation 1:1.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tehran University of Medical Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Boston University
- Responsible party
- Sponsor
- Investigators
- Mohamadali Sahraian, MD, Study chair, Multiple Sclerosis Research Center, Tehran University of Medical SciencesZhila Maghbooli, PhD, Principal investigator, Multiple Sclerosis Research Center, Tehran University of Medical SciencesMichael F Holick, PhD,MD, Principal investigator, Boston University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05340985
- Sponsor's protocol ID
- 1400-3-233-56129
- Status last verified
- Feb 2022
- First submitted
- 2 Mar 2022
- Last updated
- 22 Apr 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05340985
- Acronym / sponsor ID
- 1400-3-233-56129
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Tehran University of Medical SciencesUniversity, hospital or other
- Collaborators
- Boston University
- Study start
- Jul 2022 (estimated)
- Primary completion
- Jun 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 22 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- This is a randomized clinical trial with a parallel group and allocation 1:1.
| Arm | Type | Receives |
|---|---|---|
| 25(OH)D3 (Calcifediol) | Experimental | Dietary Supplement: 25(OH)D350 micrograms per day 25(OH)D3 or vitamin D hydroxylated for 24 weeks |
| Cholecalciferol | Experimental | Dietary Supplement: vitamin D350 micrograms (2000IU) per day Cholecalciferol for 24 Weeks |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- MS type: relapsing-remitting MS (RRMS)
- older than 18 year-old
- Vitamin D deficiency/insufficiency (25(OH)D<30 ng/ml
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 25(OH)D3Also: vitamin D analogcalcifediol | Dietary supplement | 25(OH)D3 (Calcifediol) |
| vitamin D3Also: activated 7-dehydrocholesterolCholecalciferol | Dietary supplement | Cholecalciferol |
Primary outcome
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
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.
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
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
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
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.
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 secondary outcomes
needing hospitalization
Time frame: 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
effective in rapidly raising circulating levels of 25(OH)D3
Time frame: 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
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mohamadali Sahraian, MD study chair
Multiple Sclerosis Research Center, Tehran University of Medical Sciences
Zhila Maghbooli, PhD principal investigator
Multiple Sclerosis Research Center, Tehran University of Medical Sciences
Michael F Holick, PhD,MD principal investigator
Boston University
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing 25(OH)D3 and vitamin D3 in people with Multiple Sclerosis, Relapsing-Remitting and Adult ALL, run by Tehran University of Medical Sciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zhila Maghbooli (00989121973516, zhilayas@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of relapses (time frame: 6 months (baseline and end of 6th month) in each intervention arm). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2022.