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Trial record 8 of 27 for:    multiple sclerosis | vitamin D

Vitamin D Supplementation in Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT01490502
Recruitment Status : Recruiting
First Posted : December 13, 2011
Last Update Posted : September 29, 2017
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Relapsing Remitting Multiple Sclerosis Drug: Vitamin D3 Phase 3

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 Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 172 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial of Vitamin D Supplementation in Multiple Sclerosis
Study Start Date : March 2012
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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).

Outcome Measures

Primary Outcome Measures :
  1. Proportion of subjects that experiences a relapse [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Annualized relapse rate [ Time Frame: 2 years ]
  2. Number of relapses requiring treatment [ Time Frame: 2 years ]
  3. Number of new T2 lesions [ Time Frame: In the two-year study, compared to baseline ]
  4. 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.

  5. Change in MS Functional Composite Score [ Time Frame: Over the two-year study compared to baseline ]
  6. Change in low-contrast acuity [ Time Frame: Over the two-year study compared to baseline ]
  7. Change in health-related quality of life [ Time Frame: Over the two-year study compared to baseline ]
  8. Change in brain parenchymal volume [ Time Frame: Over the two-year study compared to baseline ]
  9. Change in normalized gray matter volume [ Time Frame: Over the two-year study compared to baseline ]
  10. Change in cortical thickness [ Time Frame: Over the two year study compared to baseline ]
  11. Development of hypercalcemia/related adverse effects [ Time Frame: 2 years ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01490502

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

United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States
Contact: Emmanuelle Waubant, MD, PhD         
Contact       Emmanuelle.Waubant@ucsf.edu   
Principal Investigator: Emmanuelle Waubant, MD, PhD         
Stanford University Completed
Stanford, California, United States
United States, Connecticut
Yale University Completed
New Haven, Connecticut, United States
United States, Maryland
Anne Arundel Health System Research Institute Completed
Annapolis, Maryland, United States
Johns Hopkins University School of Medicine Recruiting
Baltimore, Maryland, United States
Contact: Madiha Qutab       mqutab1@jhmi.edu   
Principal Investigator: Ellen M Mowry, MD, MCR         
United States, Massachusetts
University of Massachusetts Recruiting
Worcester, Massachusetts, United States
Contact: Melissa Adams, RN       Melissa.Adams@umassmemorial.org   
Principal Investigator: Peter Riskind, MD         
United States, Missouri
Washington University St. Louis Recruiting
Saint Louis, Missouri, United States
Contact: Susan Fox, CCRP       foxs@neuro.wustl.edu   
Principal Investigator: Anne Cross, MD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Kaho Onomichi       ko2418@cumc.columbia.edu   
Principal Investigator: Claire Riley, MD         
Mount Sinai School of Medicine Recruiting
New York, New York, United States
Contact: Ruthie Perez       Ruthie.Perez@mssm.edu   
Principal Investigator: Michelle Fabian, MD         
University of Rochester Recruiting
Rochester, New York, United States
Contact: Cindy Irish, RN, MSCN, CCRC       Cindy_Irish@URMC.Rochester.edu   
Principal Investigator: Andrew Goodman, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States
Contact: Susan Sharp       Sharps@ccf.org   
Principal Investigator: Daniel Ontaneda, MD         
United States, Oregon
Oregon Health Sciences University Completed
Portland, Oregon, United States
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States
Contact: Lauren Mace       Lauren.Mace@uphs.upenn.edu   
Principal Investigator: Clyde Markowitz, MD         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States
Contact: Margaret Keller, RN, MS       MFK8E@hscmail.mcc.virginia.edu   
Principal Investigator: David Jones, MD         
United States, Washington
Swedish Medical Center Recruiting
Seattle, Washington, United States
Contact: Caryl Tongco, CCRC       Caryl.Tongco@swedish.org   
Contact: Yuriko Courtney       Yuriko.Courtney@swedish.org   
Principal Investigator: Peiqing Qian, MD         
Sponsors and Collaborators
Johns Hopkins University
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
Principal Investigator: Ellen M Mowry, MD, MCR Johns Hopkins University
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01490502     History of Changes
Other Study ID Numbers: NMSS 4407A2/1
First Posted: December 13, 2011    Key Record Dates
Last Update Posted: September 29, 2017
Last Verified: September 2017

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