Clinical trial NCT05340985: 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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Multiple Sclerosis, Relapsing-Remitting
Adult ALL
Vitamin D3 Deficiency
Lead sponsor: Tehran University of Medical Sciences
Sponsor class: OTHER
Collaborators: name: Boston University
First posted: 2022-04-22
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized clinical trial with a parallel group and allocation 1:1.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of relapses
timeFrame: 6 months (baseline and end of 6th month) in each intervention arm
measure: disability
timeFrame: 6 months (baseline and end of 6th month) in each intervention arm
measure: Change in MRI parameters
timeFrame: 6 months (baseline and end of 6th month) in each intervention arm
measure: changing in brain parameters of Diffusion tensor imaging (DTI)
timeFrame: 6 months (baseline and end of 6th month) in each intervention arm
measure: changing in Cognition
timeFrame: 6 months (baseline and end of 6th month) in each intervention arm
measure: CD4+ T cell response
timeFrame: 6 months (baseline and end of 6th month) in each intervention arm
measure: Differential gene expression
timeFrame: 6 months (baseline and end of 6th month) in each intervention arm
Secondary outcomes:
measure: needing hospitalization
timeFrame: 6 months (baseline and end of 6th month) in each intervention arm
measure: changing in quality of life
timeFrame: 6 months (baseline and end of 6th month) in each intervention arm
measure: effective in rapidly raising circulating levels of 25(OH)D3
timeFrame: 6 months (baseline and end of 6th month) in each intervention arm
measure: changing in the circulating levels of interleukin 17 as a inflammatory marker
timeFrame: 6 months (baseline and end of 6th month) in each intervention arm
measure: changing in the levels of interleukin 10 as anti- inflammatory marker
timeFrame: 6 months (baseline and end of 6th month) in each intervention arm
measure: changing in the levels of Tumor Necrosis Factor alpha (TNF-a) as an inflammatory marker related the T-CD4 subsets
timeFrame: 6 months (baseline and end of 6th month) in each intervention arm
Other outcomes:
Locations:
Study officials:
affiliation: Multiple Sclerosis Research Center, Tehran University of Medical Sciences
name: Mohamadali Sahraian, MD
role: STUDY_CHAIR
affiliation: Multiple Sclerosis Research Center, Tehran University of Medical Sciences
name: Zhila Maghbooli, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston University
name: Michael F Holick, PhD,MD
role: PRINCIPAL_INVESTIGATOR
References: