Intervention: Cholecalciferol
Trial phase: Phase 3
ATC code: A11CC05 | A11CC55 | M05BB03 | M05BB04 | M05BB05 | M05BB07 | M05BB08 | M05BB09 | M05BX53
SMILES: [H][C@@]12CC[C@]([H])([C@H](C)CCCC(C)C)[C@@]1(C)CCC/C2=C\C=C1\C[C@@H](O)CCC1=C
Sex: All
Age groups: Adult
Healthy volunteers: No
Participants at risk: 83
Group description: Vitamin D3: 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).
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/UCM225130.pdf).
Serum calcium >0.2 mg/dL above upper limit of normal.