Vitamin D Supplementation in Multiple Sclerosis

NCT01490502 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: NA_00049137
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 16

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.

Conditions

Relapsing Remitting Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Proportion of Subjects That Experience a Relapse

  Confirmed relapse defined as new or worsening symptoms referable to the central nervous system, lasting at least 24 hours, occurring at least 30 days since the prior attack, accompanied by worsening of the EDSS (\>= 0.5 points) or in the Functional Systems (FS) scales (2 points on at least one FS scale or 1 point on \>= two FS scales).

  2 years

Secondary Outcomes (12)

• Annualized Relapse Rate

  2 years

• Number of Relapses Requiring Treatment

  2 years

• Number of New or Enlarging T2 Lesions

  2 years

• Proportion of Participants With Sustained Disability Progression

  2 years

• Change in Multiple Sclerosis Functional Composite (MSFC) Score

  2 years

Study Arms (2)

Low-dose vitamin D3

ACTIVE COMPARATOR

Drug: Vitamin D3

High-dose vitamin D3

ACTIVE COMPARATOR

Drug: Vitamin D3

Interventions

Vitamin D3 DRUG

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).

High-dose vitamin D3; Low-dose vitamin D3

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Oregon Health and Science University: collaborator
• University of California, San Francisco: collaborator
• Washington University School of Medicine: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• University of Pennsylvania: collaborator
• Yale University: collaborator
• The Cleveland Clinic: collaborator
• University of Rochester: collaborator
• Stanford University: collaborator
• University of Virginia: collaborator
• Swedish Medical Center: collaborator
• Anne Arundel Health System Research Institute: collaborator
• Columbia University: collaborator
• University of Massachusetts, Worcester: collaborator
• Dignity Health: collaborator

Study Sites (16)

Dignity Health Medical Foundation

Carmichael, California, United States

Location

University of California, San Francisco

San Francisco, California, United States

Location

Stanford University

Stanford, California, United States

Location

Yale University

New Haven, Connecticut, United States

Location

Anne Arundel Health System Research Institute

Annapolis, Maryland, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Location

University of Massachusetts

Worcester, Massachusetts, United States

Location

Washington University St. Louis

St Louis, Missouri, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Mount Sinai School of Medicine

New York, New York, United States

Location

University of Rochester

Rochester, New York, United States

Location

Cleveland Clinic

Cleveland, Ohio, United States

Location

Oregon Health Sciences University

Portland, Oregon, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Location

University of Virginia

Charlottesville, Virginia, United States

Location

Swedish Medical Center

Seattle, Washington, United States

Location

Related Publications (2)

• Cassard SD, Fitzgerald KC, Qian P, Emrich SA, Azevedo CJ, Goodman AD, Sugar EA, Pelletier D, Waubant E, Mowry EM. High-dose vitamin D3 supplementation in relapsing-remitting multiple sclerosis: a randomised clinical trial. EClinicalMedicine. 2023 Apr 13;59:101957. doi: 10.1016/j.eclinm.2023.101957. eCollection 2023 May.

  PMID: 37125397 DERIVED

• 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.

  PMID: 25311447 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Results Point of Contact

• Title: Sandra D. Cassard, ScD
• Organization: The Johns Hopkins University School of Medicine

scassar1@jhmi.edu

443-287-4353

Study Officials

• Ellen M Mowry, MD, MCR

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2011
• First Posted: December 13, 2011
• Study Start: March 1, 2012
• Primary Completion: May 15, 2021
• Study Completion: May 15, 2021
• Last Updated: September 28, 2022
• Results First Posted: September 28, 2022

Record last verified: 2022-09

Locations

US (16)