Vitamin D3

• Vitamin D is a type of hormone and a powerful mediator of immune function. The data documenting an association between low Vitamin D and high MS risk, relapses, disability, and CNS inflammation now appear to be strong, consistent, and reproducible. Data from a number of areas of investigation suggests that Vitamin D may be one underlying common factor that begins to make sense of the large amount of data on the geographic distribution of susceptibility to MS.
  
  
• Genetically, a link appears to exist between changes in the genes involved in the synthesis of the Vitamin D hormone and the Vitamin D hormone receptor, and the risk of developingMS. The strongest genetic risk factor for MS is a specific gene (HLA DRB1*1501), whose activity appears to be influenced by Vitamin D.
  
  
• Following a review published in 2010, cumulative evidence led to a number of new clinical trials, mostly using Vitamin D as an add-on to existing therapies in Phase IV studies.
  
  
• Published in August 2011, an importantMS breakthrough has found that Vitamin D directly terminates production of disease-causing proteins. When Vitamin D is given tomice with EAE (an animalmodel ofMS), it blocks the gene that encodes IL-17, stopping its production. IL-17 appears to be amajor inflammatory component in MS. This breakthrough also demonstrates that Vitamin D increases suppressive T cells that combat inflammation.
  
  
• A Phase II study that is currently recruiting participants is investigating whether Vigantol® oil, a form of Vitamin D hormone supplement (cholecalciferol), provides any added benefit when given in conjunction with Rebif. The study will have 348 participants; it began in February 2011 and is scheduled for completion inMarch 2014. Primary outcome measures are the mean change from baseline in the total volume of T2 lesions at week 48 and the proportion of relapse-free subjects at week 96. Secondary outcome measures include sustained disability progression, MRI measures of disease progression, the proportion of subjects free from disease activity at 96 weeks, and changes in cognitive function.
  
  
• The French CHOLINE Phase II study of 250 individuals with RRMS who are receiving ongoing treatment with Rebif began in January 2010 and is scheduled for completion in December 2013. Its primary outcome measure is a reduction in relapse rate; secondary outcome measures include the time to a first documented relapse, the mean number of relapses per subject per year, the number of relapse-free patients after two years of treatment,MRI measures of progression and lesion load, and change in quality of life.
  
  
• A Finnish Phase IV study with 70 participants is investigating cholecalciferol (Vitamin D3) as an add-on treatment to Betaseron in RRMS. It began inMarch 2008 and was scheduled to end in June 2011. Its primary outcome measure is biochemical; a secondary measure is the number of gadolinium-enhancing lesions and/or new enlarging lesions.
  
  
• A small Phase IV study of 100 individuals with RRMS being treated with beta interferon has as its primary outcome measure whether Vitamin D supplementation may reduce or eliminate flu-like symptoms and injection-site reactions from the interferon. It will also determine any effects on EDSS progression, relapse rate, and quality of life. The study began in October 2010 and is scheduled for completion in October 2011.
  
  
• A small Phase I study in 40 individuals with MS, designed to determine the safety and immunologic effects of supplementation with low- (400 mg) and high-dose (10,000 mg) cholecalciferol (Vitamin D3), is currently recruiting participants whose serum levels of Vitamin D indicate that they are good candidates for supplementation. The study began in March 2010 and is scheduled for completion in December 2011. The primary outcome measure is to determine the safety of high-dose cholecalciferol and to assess the effects of cholecalciferol supplementation on serum immune markers; its clinical effects will also be assessed.