Pharmacokinetics of Vitamin D in Multiple Sclerosis and in Health

• ClinicalTrials.gov Identifier: NCT01667796
• Recruitment Status: Completed
• First Posted: August 17, 2012
• Results First Posted: February 1, 2016
• Last Update Posted: March 5, 2019
• Sponsor: Johns Hopkins University
• Collaborators: University of California, San Francisco; National Multiple Sclerosis Society
• Information provided by (Responsible Party): Johns Hopkins University

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.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis, Relapsing-remitting	Dietary Supplement: Vitamin D3	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Pharmacodynamic and Immunologic Effects of Vitamin D Supplementation in Patients With Multiple Sclerosis and Healthy Controls
• Study Start Date: November 2010
• Actual Primary Completion Date: March 2014
• Actual Study Completion Date: March 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change in Mean Serum Level of 25-hydroxyvitamin D [ Time Frame: 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 Outcome Measures :

1. Change in Percentages of T Cell Subsets (IFNγ+ and IL-17+) [ Time Frame: 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).
2. Gene Expression Microarray [ Time Frame: 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.
3. Change in Cytokine Levels [ Time Frame: 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.
4. Change in Percentage of B Cells [ Time Frame: 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.

Eligibility Criteria

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

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)

Contacts and Locations

Locations

United States, California

University of California, San Francisco

San Francisco, California, United States, 94143

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

Johns Hopkins University

University of California, San Francisco

National Multiple Sclerosis Society

Investigators

• Principal Investigator: Ellen M Mowry, MD, MCR; Johns Hopkins University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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). pii: 95302. doi: 10.1172/jci.insight.95302.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT01667796
• Other Study ID Numbers: NA_00049428; FG-1507-05231 ( Other Grant/Funding Number: National Multiple Sclerosis Society )
• First Posted: August 17, 2012
• Results First Posted: February 1, 2016
• Last Update Posted: March 5, 2019
• Last Verified: March 2019

Keywords provided by Johns Hopkins University:

Multiple sclerosis; Healthy controls; Pharmacokinetics; Vitamin D

Additional relevant MeSH terms:

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Vitamin D; Cholecalciferol; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents