Multiple Sclerosis, Relapsing-remitting
Conditions
Keywords
Multiple sclerosis, Healthy controls, Pharmacokinetics, Vitamin D
Brief summary
This is a pilot study of oral vitamin D supplementation to determine if patients with Multiple Sclerosis (MS) and healthy individuals attain a similar increase in serum 25-hydroxyvitamin D levels. The investigators will also assess whether the immunologic or relevant gene expression response to oral vitamin D supplementation differs in patients with MS and healthy controls.
Interventions
DIETARY_SUPPLEMENTVitamin D3
Sponsors
University of California, San Francisco
National Multiple Sclerosis Society
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Female * Healthy or multiple sclerosis * Aged 18 to 60 * Body mass index is between 18 kg/m2 and 30 kg/m2 * Screening 25-hydroxyvitamin D level ≤ 75 nmol/L (30 ng/mL) * White race * Non-Hispanic ethnicity * Willing to use birth control during study * Willing to not use tanning bed during study If subject has multiple sclerosis: * Relapsing-remitting MS, as defined by McDonald 2005 criteria * Screening Expanded Disability Status Scale score ≤ 3.0 * Using no medication for MS, or taking Copaxone, (glatiramer acetate), interferons, or natalizumab
Exclusion criteria
* Pregnant or nursing * Taking multivitamin & unwilling to remain off it during study * Taking cod liver oil & unwilling to remain off it during study * On a fat-restricted diet * History of renal disease or nephrolithiasis (kidney stones) * History of liver disease * Taking thiazide diuretics * History of hyperthyroidism * History of infection with Mycobacterium species * History of sarcoidosis * History of cancer * History of cardiac disease * History of HIV * History of gastrointestinal disorder * Taking medications that interfere with gastrointestinal absorption * Cigarette smoker in past month * Use of illicit drugs in past month * Use of steroids in past month * History of hypercalcemia, and screening serum calcium ≤ 10 mg/dL (UCSF) or ≤ 10.7 mg/dL (Johns Hopkins) * History of hypercalciuria * Evidence of anemia (Hgb \<11.0 g/dL) * History of other serious medical conditions * Taking medications that involve the P450 system or may interact with vitamin D (digoxin, diltiazem, verapamil, cimetidine, heparin, or low-molecular weight heparin) * Other concerns about safety from the perspective of the treating physician If subject has MS: -History of major heat sensitivity (leading to sun-avoidant behaviors)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Serum Level of 25-hydroxyvitamin D | Baseline to 90 days | Generalized estimating equations (GEE) with an autoregressive with lag one correlation matrix were used to compare the serially-measured serum 25(OH)D levels between MS patients and Healthy Controls (HCs) to take into account repeated measures and within-subject correlations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percentages of T Cell Subsets (IFNγ+ and IL-17+) | Baseline, 90 days | Analyzed the mean percentage change in IFNγ+ and IL-17+ cluster of differentiation 4 (CD4) + cells (post- versus pre- supplementation). This represents a change between two time points (90 days versus baseline). |
| Gene Expression Microarray | 90 days | We had initially planned to do whole blood gene expression. The experience gained by the laboratory that was to perform this since the original trial was planned was that this measure is too noisy and would not yield meaningful results. Thus, this analysis will no longer be conducted. |
| Change in Cytokine Levels | 90 days | The original plan had been to measure the change in basic serum cytokine levels (e.g. IL-17, interferon gamma; IL-10; pg/microliter). However, due to emerging data suggesting low utility of these measures, this plan was abandoned. |
| Change in Percentage of B Cells | 90 days | The change in percentage (day 90-baseline) was originally planned for study. Due to the limited number of patients with samples this plan was abandoned. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MS Subjects Female subjects with MS | 27 |
| Healthy Controls Female subjects without MS | 30 |
| Total | 57 |
Baseline characteristics
| Characteristic | MS Subjects | Total | Healthy Controls |
|---|---|---|---|
| Age, Continuous | 40.2 years STANDARD_DEVIATION 9.2 | 38.9 years STANDARD_DEVIATION 10.8 | 37.9 years STANDARD_DEVIATION 12.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 57 Participants | 30 Participants |
| Region of Enrollment United States | 27 participants | 57 participants | 30 participants |
| Sex: Female, Male Female | 27 Participants | 57 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 27 | 1 / 30 |
| serious Total, serious adverse events | 0 / 27 | 0 / 30 |
Outcome results
Primary
Change in Mean Serum Level of 25-hydroxyvitamin D
Generalized estimating equations (GEE) with an autoregressive with lag one correlation matrix were used to compare the serially-measured serum 25(OH)D levels between MS patients and Healthy Controls (HCs) to take into account repeated measures and within-subject correlations.
Time frame: Baseline to 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MS Subjects | Change in Mean Serum Level of 25-hydroxyvitamin D | 65.9 nmol/L | Standard Deviation 5.9 |
| Healthy Controls | Change in Mean Serum Level of 25-hydroxyvitamin D | 82.4 nmol/L | Standard Deviation 5.2 |
p-value: 0.001univariate generalized estimating equati
p-value: 0.008Generalized estimating equation
Secondary
Change in Cytokine Levels
The original plan had been to measure the change in basic serum cytokine levels (e.g. IL-17, interferon gamma; IL-10; pg/microliter). However, due to emerging data suggesting low utility of these measures, this plan was abandoned.
Time frame: 90 days
Population: Cytokine levels data were not analyzed and are no longer planned to be measured as outcomes.
Secondary
Change in Percentage of B Cells
The change in percentage (day 90-baseline) was originally planned for study. Due to the limited number of patients with samples this plan was abandoned.
Time frame: 90 days
Population: B Cell data were not analyzed and are no longer planned to be measured as outcomes.
Secondary
Change in Percentages of T Cell Subsets (IFNγ+ and IL-17+)
Analyzed the mean percentage change in IFNγ+ and IL-17+ cluster of differentiation 4 (CD4) + cells (post- versus pre- supplementation). This represents a change between two time points (90 days versus baseline).
Time frame: Baseline, 90 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MS Subjects | Change in Percentages of T Cell Subsets (IFNγ+ and IL-17+) | mean percentage change in IFNγ+ CD4+ cells | -5.2 percentage of cells | Standard Deviation 4.2 |
| MS Subjects | Change in Percentages of T Cell Subsets (IFNγ+ and IL-17+) | mean percentage change in IL-17+ CD4+ cells | 0.21 percentage of cells | Standard Deviation 0.77 |
| Healthy Controls | Change in Percentages of T Cell Subsets (IFNγ+ and IL-17+) | mean percentage change in IFNγ+ CD4+ cells | -13.2 percentage of cells | Standard Deviation 3.2 |
| Healthy Controls | Change in Percentages of T Cell Subsets (IFNγ+ and IL-17+) | mean percentage change in IL-17+ CD4+ cells | -0.17 percentage of cells | Standard Deviation 1.14 |
Secondary
Gene Expression Microarray
We had initially planned to do whole blood gene expression. The experience gained by the laboratory that was to perform this since the original trial was planned was that this measure is too noisy and would not yield meaningful results. Thus, this analysis will no longer be conducted.
Time frame: 90 days
Population: We had initially planned to do whole blood gene expression. The experience gained by the laboratory that was to perform this since the original trial was planned was that this measure is too noisy and would not yield meaningful results. Thus, this analysis will no longer be conducted.