Clinical trial NCT00940719: Vitamin D3 Supplementation and the T Cell Compartment in Multiple Sclerosis (MS)
Official title: The Effects of Vitamin D3 Supplementation on the T Cell Compartment in Multiple Sclerosis; a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Regulatory T cell function
Vitamin D
Vitamin D3
25-hydroxyvitamin D
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Orbis Medical Centre
First posted: 2009-07-16
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: In patients with Relapsing Remitting Multiple Sclerosis (RRMS), the investigators observed a positive correlation between regulatory T cell (Treg) function and vitamin D status. The present goal is to assess whether Treg function improves on supplementation with vitamin D3.

Detailed description: In several studies, Multiple Sclerosis (MS) incidence and disease activity has been related with vitamin D status. We observed that RRMS patients who remained relapse free before blood collection had a better vitamin D status than patients who experienced relapses (Smolders et al. Mult Scler 2008;17:1220-1224). Since vitamin D3 is a potent promotor of T cell regulation in vitro (Smolders et al. J Neuroimmunol 2008;194:7-17), we hypothesised that a promotion of Treg function in MS patients might underlie its association with MS disease activity. In a cohort of RRMS patients, we observed a positive correlation of Treg function with vitamin D status (Smolders et al. PLoS ONE 2009;4:e6635). Furthermore, vitamin D status correlated positively with a Th1/Th2-balance which was more directed towards Th2. In the present study, we will assess whether treatment of RRMS patients with vitamin D3 promotes T cell regulation.

In the present study, RRMS patients will be supplemented with vitamin D3, and regulatory T cell tests will be performed before and after supplementation.

Eligibility criteria: Inclusion Criteria:

* Relapsing Remitting MS (Revised MCDonald criteria 2005)
* Age \> 18 years

Exclusion Criteria:

* Progressive MS phenotype
* Abnormalities of vitamin D hormonal system other than low dietary intake or limited sun exposure
* Intake of drugs that influence vitamin D homeostasis other than corticosteroids
* Conditions with in increased susceptibility to hypercalcemia
* Alcohol or drug abuse
* Pregnancy or the intention to become pregnant within the study period

Primary outcomes:
measure: T cell regulation
timeFrame: 3 months
Secondary outcomes:
measure: serum 25-hydroxyvitamin D levels
timeFrame: 3 months
measure: calcium metabolism
timeFrame: 3 months
Other outcomes:
Locations:
city: Sittard
country: Netherlands
facility: Orbis Medical Center
Study officials:
affiliation: Orbis Medical Center Sittard, Maastricht Univeristy Medical Center Maastricht
name: Raymond Hupperts, M.D., Ph.D.
role: STUDY_DIRECTOR
affiliation: Maastricht University Medical Center
name: Joost Smolders, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Smolders J, Menheere P, Kessels A, Damoiseaux J, Hupperts R. Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis. Mult Scler. 2008 Nov;14(9):1220-4. doi: 10.1177/1352458508094399. Epub 2008 Jul 24.
citation: Smolders J, Damoiseaux J, Menheere P, Hupperts R. Vitamin D as an immune modulator in multiple sclerosis, a review. J Neuroimmunol. 2008 Feb;194(1-2):7-17. doi: 10.1016/j.jneuroim.2007.11.014. Epub 2008 Jan 4.
citation: Smolders J, Thewissen M, Peelen E, Menheere P, Tervaert JW, Damoiseaux J, Hupperts R. Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis. PLoS One. 2009 Aug 13;4(8):e6635. doi: 10.1371/journal.pone.0006635.
citation: Smolders J, Menheere P, Thewissen M, Peelen E, Tervaert JW, Hupperts R, Damoiseaux J. Regulatory T cell function correlates with serum 25-hydroxyvitamin D, but not with 1,25-dihydroxyvitamin D, parathyroid hormone and calcium levels in patients with relapsing remitting multiple sclerosis. J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):243-6. doi: 10.1016/j.jsbmb.2010.03.001. Epub 2010 Mar 6.
citation: Smolders J, Peelen E, Thewissen M, Cohen Tervaert JW, Menheere P, Hupperts R, Damoiseaux J. Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis. PLoS One. 2010 Dec 13;5(12):e15235. doi: 10.1371/journal.pone.0015235.