Vitamin D Supplementation in Multiple Sclerosis

Tracking Information
First Submitted Date ICMJE	December 6, 2011
First Posted Date ICMJE	December 13, 2011
Last Update Posted Date	September 28, 2018
Study Start Date ICMJE	March 2012
Estimated Primary Completion Date	March 2019 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 12, 2011)	Proportion of subjects that experiences a relapse [ Time Frame: 2 years ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01490502 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 10, 2012)	Annualized relapse rate [ Time Frame: 2 years ]; Number of relapses requiring treatment [ Time Frame: 2 years ]; Number of new T2 lesions [ Time Frame: In the two-year study, compared to baseline ]; Occurrence of sustained disability progression [ Time Frame: At years 1 and 2, compared to baseline ]A patient will be considered to have had sustained progression of disability if there is an increase in the Expanded Disability Status Scale score at month 12 by at least 1.0 point that is confirmed on the final examination one year later.; Change in MS Functional Composite Score [ Time Frame: Over the two-year study compared to baseline ]; Change in low-contrast acuity [ Time Frame: Over the two-year study compared to baseline ]; Change in health-related quality of life [ Time Frame: Over the two-year study compared to baseline ]; Change in brain parenchymal volume [ Time Frame: Over the two-year study compared to baseline ]; Change in normalized gray matter volume [ Time Frame: Over the two-year study compared to baseline ]; Change in cortical thickness [ Time Frame: Over the two year study compared to baseline ]; Development of hypercalcemia/related adverse effects [ Time Frame: 2 years ]
Original Secondary Outcome Measures ICMJE; (submitted: December 12, 2011)	Annualized relapse rate [ Time Frame: 2 years ]; Number of relapses requiring treatment [ Time Frame: 2 years ]; Number of new T2 lesions [ Time Frame: In the two-year study, compared to baseline ]; Occurrence of sustained disability progression [ Time Frame: At years 1 and 2, compared to baseline ]A patient will be considered to have had sustained progression of disability if there is an increase in the Expaned Disability Status Scale score at month 12 by at least 1.0 point that is confirmed on the final examination one year later.; Change in MS Functional Composite Score [ Time Frame: Over the two-year study compared to baseline ]; Change in low-contrast acuity [ Time Frame: Over the two-year study compared to baseline ]; Change in health-related quality of life [ Time Frame: Over the two-year study compared to baseline ]; Change in brain parenchymal volume [ Time Frame: Over the two-year study compared to baseline ]; Change in normalized gray matter volume [ Time Frame: Over the two-year study compared to baseline ]; Change in cortical thickness [ Time Frame: Over the two year study compared to baseline ]; Development of hypercalcemia/related adverse effects [ Time Frame: 2 years ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Vitamin D Supplementation in Multiple Sclerosis
Official Title ICMJE	A Randomized Controlled Trial of Vitamin D Supplementation in Multiple Sclerosis
Brief 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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Relapsing Remitting Multiple Sclerosis
Intervention ICMJE	Drug: 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).
Study Arms	Active Comparator: Low-dose vitamin D3 Intervention: Drug: Vitamin D3; Active Comparator: High-dose vitamin D3 Intervention: Drug: Vitamin D3
Publications *	Bhargava P, Cassard S, Steele SU, Azevedo C, Pelletier D, Sugar EA, Waubant E, Mowry EM. The vitamin D to ameliorate multiple sclerosis (VIDAMS) trial: study design for a multicenter, randomized, double-blind controlled trial of vitamin D in multiple sclerosis. Contemp Clin Trials. 2014 Nov;39(2):288-93. doi: 10.1016/j.cct.2014.10.004. Epub 2014 Oct 12.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Recruiting
Estimated Enrollment ICMJE; (submitted: December 12, 2011)	172
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	March 2019
Estimated Primary Completion Date	March 2019 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 50 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact: Ellen M Mowry, MD, MCR vitamindtrialms@jhmi.edu Contact: Sandra D Cassard, ScD vitamindtrialms@jhmi.edu
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01490502
Other Study ID Numbers ICMJE	NMSS 4407A2/1
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Johns Hopkins University
Study Sponsor ICMJE	Johns Hopkins University
Collaborators ICMJE	Oregon Health and Science University; University of California, San Francisco; Washington University School of Medicine; Icahn School of Medicine at Mount Sinai; University of Pennsylvania; Yale University; The Cleveland Clinic; University of Rochester; Stanford University; University of Virginia; Swedish Medical Center; Anne Arundel Health System Research Institute; Columbia University; University of Massachusetts, Worcester; Dignity Health
Investigators ICMJE	Principal Investigator: Ellen M Mowry, MD, MCR Johns Hopkins University
PRS Account	Johns Hopkins University
Verification Date	September 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP