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Pharmacokinetics of Vitamin D in Multiple Sclerosis and in Health

Primary Purpose

Multiple Sclerosis, Relapsing-remitting

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Vitamin D3
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Multiple Sclerosis, Relapsing-remitting focused on measuring Multiple sclerosis, Healthy controls, Pharmacokinetics, Vitamin D

Eligibility Criteria

18 Years - 60 Years (Adult)FemaleAccepts Healthy Volunteers

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)

Sites / Locations

  • University of California, San Francisco
  • Johns Hopkins University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vitamin D3

Arm Description

Both those with MS and healthy controls will be given vitamin D3 5000 IU/day by mouth for 90 days.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).
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.
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.
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.

Full Information

First Posted
August 13, 2012
Last Updated
March 1, 2019
Sponsor
Johns Hopkins University
Collaborators
University of California, San Francisco, National Multiple Sclerosis Society
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1. Study Identification

Unique Protocol Identification Number
NCT01667796
Brief Title
Pharmacokinetics of Vitamin D in Multiple Sclerosis and in Health
Official Title
Pharmacodynamic and Immunologic Effects of Vitamin D Supplementation in Patients With Multiple Sclerosis and Healthy Controls
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
November 2010 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
University of California, San Francisco, National Multiple Sclerosis Society

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Relapsing-remitting
Keywords
Multiple sclerosis, Healthy controls, Pharmacokinetics, Vitamin D

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vitamin D3
Arm Type
Experimental
Arm Description
Both those with MS and healthy controls will be given vitamin D3 5000 IU/day by mouth for 90 days.
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin D3
Primary Outcome Measure Information:
Title
Change in Mean Serum Level of 25-hydroxyvitamin D
Description
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
Secondary Outcome Measure Information:
Title
Change in Percentages of T Cell Subsets (IFNγ+ and IL-17+)
Description
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
Title
Gene Expression Microarray
Description
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
Title
Change in Cytokine Levels
Description
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
Title
Change in Percentage of B Cells
Description
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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ellen M Mowry, MD, MCR
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28978801
Citation
Bhargava P, Fitzgerald KC, Calabresi PA, Mowry EM. Metabolic alterations in multiple sclerosis and the impact of vitamin D supplementation. JCI Insight. 2017 Oct 5;2(19):e95302. doi: 10.1172/jci.insight.95302.
Results Reference
derived

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Pharmacokinetics of Vitamin D in Multiple Sclerosis and in Health

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