Vitamin D Supplementation in Multiple Sclerosis

This study is currently recruiting participants.
Verified March 2014 by Johns Hopkins University
Sponsor:
Collaborators:
Oregon Health and Science University
University of California, San Francisco
Washington University School of Medicine
Mount Sinai School of Medicine
University of Pennsylvania
Yale University
The Cleveland Clinic
University of Rochester
Stanford University
University of Virginia
Swedish Medical Center
Anne Arundel Medical Center
SUNY Stony Brook
Columbia University
Information provided by (Responsible Party):
Ellen M. Mowry, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01490502
First received: December 6, 2011
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Relapsing Remitting Multiple Sclerosis
Drug: Vitamin D3
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial of Vitamin D Supplementation in Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Proportion of subjects that experiences a relapse [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Annualized relapse rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Number of relapses requiring treatment [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Number of new T2 lesions [ Time Frame: In the two-year study, compared to baseline ] [ Designated as safety issue: No ]
  • Occurrence of sustained disability progression [ Time Frame: At years 1 and 2, compared to baseline ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Change in low-contrast acuity [ Time Frame: Over the two-year study compared to baseline ] [ Designated as safety issue: No ]
  • Change in health-related quality of life [ Time Frame: Over the two-year study compared to baseline ] [ Designated as safety issue: No ]
  • Change in brain parenchymal volume [ Time Frame: Over the two-year study compared to baseline ] [ Designated as safety issue: No ]
  • Change in normalized gray matter volume [ Time Frame: Over the two-year study compared to baseline ] [ Designated as safety issue: No ]
  • Change in cortical thickness [ Time Frame: Over the two year study compared to baseline ] [ Designated as safety issue: No ]
  • Development of hypercalcemia/related adverse effects [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 172
Study Start Date: March 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Low-dose vitamin D3 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).
Active Comparator: High-dose vitamin D3 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).

Detailed Description:

Vitamin D insufficiency has recently emerged as a risk factor for susceptibility to multiple sclerosis (MS). Our 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 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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Must meet MAGNIMS criteria for relapsing-remitting MS
  2. Age 18 to 50 years
  3. EDSS score ≤ 4.0
  4. MS disease duration ≤ 10 years if McDonald RRMS; ≤ 1 year if meets MAGNIMS RRMS criteria but not McDonald RRMS criteria
  5. If the patient meets the McDonald RRMS criteria (rather than McDonald 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
  6. Females of child-bearing age must be willing to use at least one form of pregnancy prevention throughout the study.
  7. Must have had a 25-hydroxyvitamin D level of ≥ 15 ng/mL within past 30 days
  8. 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:

  1. Not be pregnant or nursing
  2. No ongoing renal or liver disease
  3. 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.
  4. No ongoing hyperthyroidism or active infection with Mycobacterium species
  5. No known gastrointestinal disease (ulcerative colitis, Crohn's disease, celiac disease/gluten intolerance) or use of medications associated with malabsorption.
  6. No history of self-reported alcohol or substance abuse in past six months.
  7. 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.
  8. No use of interferon beta or glatiramer acetate therapy for one month prior to screening
  9. No use of more than 1,000 IU vitamin D3 daily in the three months prior to screening
  10. No condition that would limit the likelihood of completing the MRI procedures
  11. 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.
  12. No steroids within a month of screening.
  13. 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).
  14. Serum calcium >0.2 mg/dL above upper limit of normal.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01490502

Contacts
Contact: Ellen M Mowry, MD, MCR vitamindtrialms@jhmi.edu
Contact: Sandra D Cassard, ScD vitamindtrialms@jhmi.edu

Locations
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States
Contact: Emmanuelle Waubant         
Principal Investigator: Emmanuelle Waubant, MD, PhD         
Stanford University Recruiting
Stanford, California, United States
Contact: Angela Campbell       ajcam@stanford.edu   
Sub-Investigator: Alexandra Goodyear, M.D.         
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States
Contact: Evangelia Louizos       e.louizos@yale.edu   
Principal Investigator: Daniel Pelletier, M.D         
United States, Maryland
Anne Arundel Medical Center Recruiting
Annapolis, Maryland, United States
Contact: Melissa Gerstenhaber       mgerste1@jhmi.edu   
Contact: Elaine Passley-Peckoo       epassleype@aahs.org   
Principal Investigator: Arash Farhadi, MD         
Johns Hopkins University School of Medicine Recruiting
Baltimore, Maryland, United States
Contact: Mary Frey       mfrey3@jhmi.edu   
Principal Investigator: Ellen M Mowry, MD, MCR         
United States, Missouri
Washington University St. Louis Recruiting
St. Louis, Missouri, United States
Contact: Susan Fox       foxs@neuro.wustl.edu   
Principal Investigator: Anne Cross, MD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Deborah Gohs       deg15@mail.cumc.columbia.edu   
Principal Investigator: Claire Riley, MD         
Mount Sinai School of Medicine Recruiting
New York, New York, United States
Contact: Shelly Phelps       Shelly.Phelps@mssm.edu   
Principal Investigator: Michelle Fabian, MD         
University of Rochester Recruiting
Rochester, New York, United States
Contact: Cindy Irish       Cindy_Irish@URMC.Rochester.edu   
Principal Investigator: Andrew Goodman, M.D.         
SUNY Stony Brook Not yet recruiting
Stony Brook, New York, United States, 11786
Contact: Diana Kaell       Diana.Kaell@stonybrookmedicine.edu   
Principal Investigator: Lauren Krupp, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States
Contact: Susan Sharp       Sharps@ccf.org   
Principal Investigator: Daniel Ontaneda, M.D.         
United States, Oregon
Oregon Health Sciences University Recruiting
Portland, Oregon, United States
Contact: Alex Lewis       lewisa@ohsu.edu   
Principal Investigator: Edward Kim, MD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States
Contact: Amber Roberts       Amber.roberts@uphs.upenn.edu   
Principal Investigator: Clyde Markowitz, MD         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States
Contact: Margaret Keller       MFK8E@hscmail.mcc.virginia.edu   
Principal Investigator: David Jones, MD         
United States, Washington
Swedish Medical Center Recruiting
Seattle, Washington, United States
Contact: Caryl Tongco       Caryl.Tongco@swedish.org   
Contact: Lauren Lennox       Lauren.Lennox@swedish.org   
Principal Investigator: Peiqing Qian, M.D.         
Sponsors and Collaborators
Johns Hopkins University
Oregon Health and Science University
University of California, San Francisco
Washington University School of Medicine
Mount Sinai School of Medicine
University of Pennsylvania
Yale University
The Cleveland Clinic
University of Rochester
Stanford University
University of Virginia
Swedish Medical Center
Anne Arundel Medical Center
SUNY Stony Brook
Columbia University
Investigators
Principal Investigator: Ellen M Mowry, MD, MCR Johns Hopkins University
  More Information

No publications provided

Responsible Party: Ellen M. Mowry, Assistant Professor of Neurology, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01490502     History of Changes
Other Study ID Numbers: NMSS 4407A2/1
Study First Received: December 6, 2011
Last Updated: March 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on April 15, 2014