Evidence map›Paper›PMID 26718578›Full record

Trial reportNeurology2016

Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis.

Elias S Sotirchos, Pavan Bhargava, Christopher Eckstein, Keith Van Haren, Moira Baynes, Achilles Ntranos, Anne Gocke, Lawrence Steinman, Ellen M Mowry, Peter A Calabresi

Open access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 11 pooled it
12.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

67 citing papers in PubMed, 11 syntheses or guidelines pooled it, 145 citations in OpenAlex.

  1. Pooled it
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  10. Vitamin D for the management of multiple sclerosis.The Cochrane database of systematic reviews · 2018
    Pooled it
  11. Guideline
  12. Trial
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  16. Exploring the effect of vitamin DMultiple sclerosis (Houndmills, Basingstoke, England) · 2018
    Trial
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7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Elias S SotirchosFrom the Department of Neurology (E.S.S., P.B., M.B., A.N., A.G., E.M.M., P.A.C.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (C.E.), Duke University School of Medicine, Durham, NC; and Department of Neurology (K.V.H., L.S.), Stanford University School of Medicine, Palo Alto, CA.
Pavan BhargavaFrom the Department of Neurology (E.S.S., P.B., M.B., A.N., A.G., E.M.M., P.A.C.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (C.E.), Duke University School of Medicine, Durham, NC; and Department of Neurology (K.V.H., L.S.), Stanford University School of Medicine, Palo Alto, CA.
Christopher EcksteinFrom the Department of Neurology (E.S.S., P.B., M.B., A.N., A.G., E.M.M., P.A.C.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (C.E.), Duke University School of Medicine, Durham, NC; and Department of Neurology (K.V.H., L.S.), Stanford University School of Medicine, Palo Alto, CA.
Keith Van HarenFrom the Department of Neurology (E.S.S., P.B., M.B., A.N., A.G., E.M.M., P.A.C.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (C.E.), Duke University School of Medicine, Durham, NC; and Department of Neurology (K.V.H., L.S.), Stanford University School of Medicine, Palo Alto, CA.
Moira BaynesFrom the Department of Neurology (E.S.S., P.B., M.B., A.N., A.G., E.M.M., P.A.C.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (C.E.), Duke University School of Medicine, Durham, NC; and Department of Neurology (K.V.H., L.S.), Stanford University School of Medicine, Palo Alto, CA.
Achilles NtranosFrom the Department of Neurology (E.S.S., P.B., M.B., A.N., A.G., E.M.M., P.A.C.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (C.E.), Duke University School of Medicine, Durham, NC; and Department of Neurology (K.V.H., L.S.), Stanford University School of Medicine, Palo Alto, CA.
Anne GockeFrom the Department of Neurology (E.S.S., P.B., M.B., A.N., A.G., E.M.M., P.A.C.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (C.E.), Duke University School of Medicine, Durham, NC; and Department of Neurology (K.V.H., L.S.), Stanford University School of Medicine, Palo Alto, CA.
Lawrence SteinmanFrom the Department of Neurology (E.S.S., P.B., M.B., A.N., A.G., E.M.M., P.A.C.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (C.E.), Duke University School of Medicine, Durham, NC; and Department of Neurology (K.V.H., L.S.), Stanford University School of Medicine, Palo Alto, CA.
Ellen M MowryFrom the Department of Neurology (E.S.S., P.B., M.B., A.N., A.G., E.M.M., P.A.C.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (C.E.), Duke University School of Medicine, Durham, NC; and Department of Neurology (K.V.H., L.S.), Stanford University School of Medicine, Palo Alto, CA.
Peter A CalabresiFrom the Department of Neurology (E.S.S., P.B., M.B., A.N., A.G., E.M.M., P.A.C.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (C.E.), Duke University School of Medicine, Durham, NC; and Department of Neurology (K.V.H., L.S.), Stanford University School of Medicine, Palo Alto, CA. calabresi@jhmi.edu.
Duke University · US

Funding

The effect of vitamin D3 on markers of oxidative stress in boys with X-linked ALDK23NS087151 · NINDS · STANFORD UNIVERSITY · PI VAN HAREN, KEITH · 2015 to 2019
$926k
The effect of vitamin D on the clinical and imaging course of multiple sclerosisK23NS067055 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MOWRY, ELLEN M. · 2010 to 2014
$881k
NINDS NIH HHS K23 NS067055).NINDS NIH HHS K23 NS087151
6 · The paper itself

Abstract

objectiveTo study the safety profile and characterize the immunologic effects of high- vs low-dose cholecalciferol supplementation in patients with multiple sclerosis (MS).

methodsIn this double-blind, single-center randomized pilot study, 40 patients with relapsing-remitting MS were randomized to receive 10,400 IU or 800 IU cholecalciferol daily for 6 months. Assessments were performed at baseline and 3 and 6 months.

resultsMean increase of 25-hydroxyvitamin D levels from baseline to final visit was larger in the high-dose group (34.9 ng/mL; 95% confidence interval [CI] 25.0-44.7 ng/mL) than in the low-dose group (6.9 ng/mL; 95% CI 1.0-13.7 ng/mL). Adverse events were minor and did not differ between the 2 groups. Two relapses occurred, one in each treatment arm. In the high-dose group, we found a reduction in the proportion of interleukin-17(+)CD4(+) T cells (p = 0.016), CD161(+)CD4(+) T cells (p = 0.03), and effector memory CD4(+) T cells (p = 0.021) with a concomitant increase in the proportion of central memory CD4(+) T cells (p = 0.018) and naive CD4(+) T cells (p = 0.04). These effects were not observed in the low-dose group.

conclusionsCholecalciferol supplementation with 10,400 IU daily is safe and tolerable in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects in MS, which include reduction of interleukin-17 production by CD4(+) T cells and decreased proportion of effector memory CD4(+) T cells with concomitant increase in central memory CD4(+) T cells and naive CD4(+) T cells. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that cholecalciferol supplementation with 10,400 IU daily is safe and well-tolerated in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects.

Indexed as

CholecalciferolImmunologic FactorsAdultCD4 Lymphocyte CountCD4-Positive T-LymphocytesDietary SupplementsDouble-Blind MethodFemaleHumansInterleukin-17MaleMiddle AgedMultiple Sclerosis, Relapsing-RemittingPilot ProjectsTreatment OutcomeVitamin D25-hydroxyvitamin DCholecalciferolIL17A protein, humanImmunologic FactorsInterleukin-17Vitamin D

Identifiers

PMID26718578
PMCPMC4776090
OpenAlexW2253002638

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.