Vitamin D Supplementation in Multiple Sclerosis
Condition: Relapsing Remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: Vitamin D3
Intervention description: 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
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 172.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must meet Magnetic Resonance Imaging in MS (MAGNIMS) criteria for relapsing-remitting
             MS

          -  Age 18 to 50 years

          -  Expanded Disability Status Scale (EDSS) score ≤ 4.0

          -  MS disease duration ≤ 10 years if McDonald Relapse Remitting Multiple Sclerosis
             (RRMS;) ≤ 1 year if meets MAGNIMS RRMS criteria but not McDonald RRMS criteria

          -  If the patient meets the McDonald RRMS criteria (rather than McDonald Clinically

        Isolated Syndrome (CIS) that is now classified as MAGNIMS MS):

          -  Must have had one clinical attack in past two years and at least one new silent T2 or
             gadolinium-enhancing lesion on brain MRI within the past year OR

          -  Must have had two clinical attacks in past two years, one of which occurred in the
             past year

          -  Females of child-bearing age must be willing to use at least one form of pregnancy
             prevention throughout the study.

          -  Must have had a 25-hydroxyvitamin D level of ≥ 15 ng/mL within past 30 days

          -  Must be willing to stop taking additional supplemental vitamin D, except as part of a
             multivitamin, and must be willing to not take cod liver oil.

        Exclusion Criteria:

          -  Not be pregnant or nursing

          -  No ongoing renal or liver disease

          -  No known history of nephrolithiasis, hypercalcemia, sarcoidosis or other serious
             chronic illness including cancer (other than basal cell or squamous cell carcinoma of
             the skin), cardiac disease, or HIV.

          -  No ongoing hyperthyroidism or active infection with Mycobacterium species

          -  No known gastrointestinal disease (ulcerative colitis, Crohn's disease, celiac
             disease/gluten intolerance) or use of medications associated with malabsorption.

          -  No history of self-reported alcohol or substance abuse in past six months.

          -  No prior history of treatment with rituximab, any chemotherapeutic agent, or total
             lymphoid irradiation. No treatment in the past six months with natalizumab,
             fingolimod, or fumarate. If patient has received glatiramer acetate, they have not
             been exposed to more than three months of treatment. No treatment with other
             unapproved therapies for MS.

          -  No use of interferon beta or glatiramer acetate therapy for one month prior to
             screening

          -  No use of more than 1,000 IU vitamin D3 daily in the three months prior to screening

          -  No condition that would limit the likelihood of completing the MRI procedures

          -  No use of thiazide diuretics, digoxin, diltiazem, verapamil, cimetidine, heparin,
             low-molecular weight heparin, phenytoin, phenobarbital, carbamazepine, routine
             corticosteroids (eg scheduled monthly steroids, daily, etc), rifampin, or
             cholestyramine.

          -  No steroids within a month of screening.

          -  Not suicidal at screening visit (ineligible if answers "yes" to question 1 of
             screening Columbia Suicide Severity Rating Scale (C-SSRS) in PAST 2 MONTHS; or answers
             "yes" to questions 2-5 on C-SSRS for PAST 6 MONTHS; or answers "yes" to suicidal
             attempts or preparatory attempts in PAST 5 YEARS ,
             http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
             CM225130.pdf).

          -  Serum calcium >0.2 mg/dL above upper limit of normal.