Adult ALL, Multiple Sclerosis, Relapsing-Remitting, Vitamin D3 Deficiency
Conditions
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.
Interventions
DIETARY_SUPPLEMENT25(OH)D3
calcifediol
DIETARY_SUPPLEMENTvitamin D3
Cholecalciferol
Sponsors
Boston University
Tehran University of Medical Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (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.
Intervention model description
This is a randomized clinical trial with a parallel group and allocation 1:1.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differential gene expression | 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 |
| Number of relapses | 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 | 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 | 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) | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| changing in quality of life | 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. |
| effective in rapidly raising circulating levels of 25(OH)D3 | 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) |
| changing in the circulating levels of interleukin 17 as a inflammatory marker | 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. |
| changing in the levels of interleukin 10 as anti- inflammatory marker | 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. |
| changing in the levels of Tumor Necrosis Factor alpha (TNF-a) as an inflammatory marker related the T-CD4 subsets | 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. |
| needing hospitalization | 6 months (baseline and end of 6th month) in each intervention arm | needing hospitalization due to remissions and exacerbations of the disease |
Contacts
Primary ContactZhila Maghbooli
Outcome results
None listed