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
试验速览
- 阶段
- 4 期
- 入组人数
- 54
- 主要终点
- Change in MRI parameters
研究概览
简要总结
Investigating the effects of hydroxyvitamin D3 on clinical, radiologic and immunomodulatory markers in MS patients: A randomized, clinical trial- a pilot study
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •MS type: relapsing-remitting MS (RRMS)
- •older than 18 year-old
- •Vitamin D deficiency/insufficiency (25(OH)D<30 ng/ml
排除标准
- •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
结局指标
主要结局
Change in MRI parameters
时间窗: 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
disability
时间窗: 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.
changing in brain parameters of Diffusion tensor imaging (DTI)
时间窗: 6 months (baseline and end of 6th month) in each intervention arm
the integrity of white matter (WM) by analyzing WM microstructure through DTI
Number of relapses
时间窗: 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
Differential gene expression
时间窗: 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
changing in Cognition
时间窗: 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
时间窗: 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.
次要结局
- changing in quality of life(6 months (baseline and end of 6th month) in each intervention arm)
- needing hospitalization(6 months (baseline and end of 6th month) in each intervention arm)
- effective in rapidly raising circulating levels of 25(OH)D3(6 months (baseline and end of 6th month) in each intervention arm)
- changing in the circulating levels of interleukin 17 as a inflammatory marker(6 months (baseline and end of 6th month) in each intervention arm)
- changing in the levels of interleukin 10 as anti- inflammatory marker(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(6 months (baseline and end of 6th month) in each intervention arm)