Vitamin D Supplementation in Multiple Sclerosis
Condition: Relapsing Remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Study type: Interventional
Phase: Phase 3

Summary: 
      Low vitamin D levels have been shown to increase a person's risk of developing multiple
      sclerosis (MS), and patients with MS who have lower vitamin D levels are at increased risk of
      having attacks. However, it is not known if giving supplemental vitamin D to those with MS
      reduces the risk of attacks, and some research suggests that vitamin D could even be harmful
      to people with MS.

      In this clinical trial, patients with relapsing-remitting MS will receive high-dose or
      low-dose oral vitamin D in addition to an approved therapy for MS, glatiramer acetate.
      Patients will be evaluated for two years, and the effect of high-dose vitamin D
      supplementation on the rate of MS attacks and on the number of new lesions and change in
      brain volume on MRI will be determined. Establishing this association will have major
      implications for the treatment of individuals with MS throughout the world.
    

Detailed description: 
      Vitamin D insufficiency has recently emerged as a risk factor for susceptibility to multiple
      sclerosis (MS). The investigator's observational data suggest that lower vitamin D levels in
      patients with relapsing-remitting MS are associated with a higher subsequent relapse rate.
      However, it is unknown if providing vitamin D supplementation to such patients leads to a
      reduction in the risk of an exacerbation. Historically, several nutritional supplements that
      appeared to be helpful in observational studies of various diseases did not demonstrate a
      benefit or were harmful in randomized trials. Further, a vitamin D response element was
      recently identified in the promoter region of Human Leukocyte Antigen (HLA)-DRB1*15, the gene
      believed to be critical to initiating the autoimmune response in MS, and 1,
      25-dihydroxyvitamin D3 increases the expression of the gene in vitro, suggesting that vitamin
      D supplementation could even be harmful in established MS.

      This is a randomized, double-blind trial of high- versus low-dose vitamin D3 supplementation
      as an add-on to glatiramer acetate in 172 patients with relapsing-remitting MS. Subjects will
      be randomized to 600 IU or 5000 IU of oral vitamin D3 daily for two years. A standardized
      brain MRI scan will be performed at baseline and at the end of the first and second years.
      The impact of high-dose vitamin D supplementation on the number of relapses, the number of
      new lesions on brain MRI, and the change in brain volume will be assessed. Establishing these
      associations will have major implications for the treatment of patients with MS throughout
      the world and will provide rationale for further investigations of the role of vitamin D in
      the immunopathogenesis of MS, possibly leading to the identification of new therapeutic
      targets.
    

Intervention name(s): Vitamin D3
Intervention type(s): Drug
Intervention description(s): Patients will be assigned to low dose (600 IU/day) versus high-dose (5000 IU/day) of vitamin D3 as an add-on therapy to glatiramer acetate (Copaxone).
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment