Relapsing Remitting Multiple SclerosisPhase 3NCT01490502
Vitamin D Supplementation in Multiple Sclerosis
A Phase 3 study testing Vitamin D3 in people with Relapsing Remitting Multiple Sclerosis, run by Johns Hopkins University at 16 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Relapsing Remitting Multiple Sclerosis
- What is being tested?
- Vitamin D3
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 172 participants
- Where
- 16 sitesUnited States
- Study dates
- Mar 2012to 15 May 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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):
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Anne Arundel Health System Research Institute
Annapolis, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland
Dignity Health Medical Foundation
Carmichael, California
University of Virginia
Charlottesville, Virginia
Cleveland Clinic
Cleveland, Ohio
Yale University
New Haven, Connecticut
Columbia University
New York, New York, 10032
Mount Sinai School of Medicine
New York, New York
University of Pennsylvania
Philadelphia, Pennsylvania
Oregon Health Sciences University
Portland, Oregon
University of Rochester
Rochester, New York
University of California, San Francisco
San Francisco, California
Swedish Medical Center
Seattle, Washington
Washington University St. Louis
St Louis, Missouri
Stanford University
Stanford, California
University of Massachusetts
Worcester, Massachusetts
About this study
Official title: A Randomized Controlled Trial of Vitamin D Supplementation in Multiple Sclerosis
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.
Read the 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.
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Being tested
- Vitamin D3
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin D3Drug
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 group | Role | What they receive |
|---|---|---|
| Low-dose vitamin D3 | Active comparator | Not described Receives: Drug: Vitamin D3 |
| High-dose vitamin D3 | Active comparator | Not described Receives: Drug: Vitamin D3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 2 years
Secondary outcomes (12)
Annualized Relapse Rate
Average relapses per year
Measured: 2 years
Number of Relapses Requiring Treatment
Measured: 2 years
Number of New or Enlarging T2 Lesions
Measured: 2 years
Proportion of Participants With Sustained Disability Progression
The Expanded Disability Status Scale (EDSS) is an ordinal clinical rating scale based on a standard neurological examination and is used to measure global neurologic impairment in people with multiple sclerosis (MS). It ranges from a minimum of 0.0 (normal examination) to 10.0 (death due to MS) in half-point increments. A participant will be considered to have had sustained progression of disability if there is an increase in the EDSS score at month 12 by at least 1.0 point that is confirmed on the final examination one year later (month 24).
Measured: 2 years
Change in Multiple Sclerosis Functional Composite (MSFC) Score
The Multiple Sclerosis Functional Composite (MSFC) is a three-part measure of disability for people with multiple sclerosis, including measures of leg function/ambulation, arm/hand function and cognitive function. The three independent measures have different units. We take the reciprocal of the arm/hand function test, and then convert all measures to Z-scores. The average of the Z-scores from each measure yields the MSFC composite Z-score. A Z-score of 0 represents the population mean and positive scores indicate less disability.
The MSFC was measured at baseline and up to 4 more times over 2 years.
Measured: 2 years
Change in Low-contrast Acuity
Low-contrast acuity was measured as binocular vision on a 2.5% Sloan chart at a distance of 2 meters. The chart is used to test the ability to discriminate gradually smaller gray letters with a 2.5% contrast level against a white background. The low-contrast acuity measure is scored as total letters read and ranges from 0 (no letters read) to 60 (all letters read). Low-contrast acuity was measured at baseline and up to 4 more times over 2 years and higher scores indicate better low-contrast acuity.
Measured: 2 years
Change in Health-related Quality of Life
The Functional Assessment of Multiple Sclerosis (FAMS) questionnaire is the quality of life (QOL) instrument used in this trial. It consists of 44 questions and the total score has a possible range of 0 to 176, with higher scores indicating better QOL. The FAMS questionnaire was obtained at baseline and up to 4 more times over 2 years.
Measured: 2 years
Change in Brain Parenchymal Volume
Measured: 2 years
Change in Normalized Gray Matter Volume
Measured: 2 years
Change in Cortical Thickness
Unable to analyze this outcome measure
Measured: 2 years
Development of Hypercalcemia
Measured: 2 years
Development of Nephrolithiasis
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2011 (estimated)
- Study startMar 2012
- Primary completion15 May 2021
- Study completion15 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Relapsing Remitting Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 172 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- 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
- Responsible party
- Sponsor
- Investigators
- Ellen M Mowry, MD, MCR, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01490502
- Sponsor's protocol ID
- NA_00049137
- Status last verified
- Sep 2022
- First submitted
- 6 Dec 2011
- Last updated
- 28 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 37125397Bhargava 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.
PubMed 25311447
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of Vitamin D Supplementation in Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT01490502
- Acronym / sponsor ID
- NA_00049137
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 172 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- 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
- Study start
- Mar 2012 (actual)
- Primary completion
- 15 May 2021 (actual)
- Study completion
- 15 May 2021 (actual)
- First posted
- 13 Dec 2011 (estimated)
- Results
- Posted 28 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low-dose vitamin D3 | Active comparator | Drug: Vitamin D3 |
| High-dose vitamin D3 | Active comparator | Drug: Vitamin D3 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin D3Patients 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). | Drug | High-dose vitamin D3, Low-dose vitamin D3 |
Primary outcome
Proportion of Subjects That Experience a Relapse
Time frame: 2 years
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).
12 secondary outcomes
Annualized Relapse Rate
Time frame: 2 years
Number of Relapses Requiring Treatment
Time frame: 2 years
Number of New or Enlarging T2 Lesions
Time frame: 2 years
Proportion of Participants With Sustained Disability Progression
Time frame: 2 years
Change in Multiple Sclerosis Functional Composite (MSFC) Score
Time frame: 2 years
Change in Low-contrast Acuity
Time frame: 2 years
Change in Health-related Quality of Life
Time frame: 2 years
Change in Brain Parenchymal Volume
Time frame: 2 years
Change in Normalized Gray Matter Volume
Time frame: 2 years
Change in Cortical Thickness
Time frame: 2 years
Development of Hypercalcemia
Time frame: 2 years
Development of Nephrolithiasis
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37125397Cassard 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.
- Derived from this study: PubMed 25311447Bhargava 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ellen M Mowry, MD, MCR principal investigator
Johns Hopkins University
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vitamin D3 in people with Relapsing Remitting Multiple Sclerosis, run by Johns Hopkins University at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Subjects That Experience a Relapse (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01490502, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2022.