Pharmacokinetics of Vitamin D in Multiple Sclerosis and in Health

Pharmacodynamic and Immunologic Effects of Vitamin D Supplementation in Patients With Multiple Sclerosis and Healthy Controls

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis, Relapsing-remitting
• Intervention / Treatment: Dietary supplement: Vitamin D3

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin D3; Both those with MS and healthy controls will be given vitamin D3 5000 IU/day by mouth for 90 days.	Dietary supplement: Vitamin D3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline, 90 days
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.	90 days
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.	90 days
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.	90 days

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: University of California, San Francisco; National Multiple Sclerosis Society

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: August 13, 2012
• First Submitted That Met QC Criteria: August 14, 2012
• First Posted (Estimate): August 17, 2012

Study Record Updates

• Last Update Posted (Actual): March 5, 2019
• Last Update Submitted That Met QC Criteria: March 1, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Vitamin D; Multiple sclerosis; Pharmacokinetics; Healthy controls
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: NA_00049428; FG-1507-05231 (Other Grant/Funding Number: National Multiple Sclerosis Society)