Title
Vitamin D3 and the Stress-axis in MS
Regulation of the Stress-axis by Vitamin D3 in Subjects With Multiple Sclerosis; a Double-blinded, Randomized, Placebo-controlled Study
Phase
Phase 2Lead Sponsor
Academic MS Center LimburgStudy Type
InterventionalStatus
TerminatedIndication/Condition
Multiple SclerosisIntervention/Treatment
vitamin d3 ...Study Participants
54Patients with multiple sclerosis (MS) have an increased risk of developing a major depression. The investigators observed a protective effect of high vitamin D levels on the risk of depression in MS. This might be driven by the effect of vitamin D on the stress-axis. Therefore, the main goal of the present study is to assess whether high dose vitamin D supplementation results in a suppression of the stress-axis, as measured by decreased levels of cortisol.
The lifetime incidence of a major depression in Multiple Sclerosis (MS) is 50%. (Patten et al. Neurology 2003; 61(11):1524-7) Our group reported a negative correlation between vitamin D status and depression score of the Hospital Anxiety and Depression Scale (HADS) in a cross-sectional dataset of Dutch MS patients. (Knippenberg et al. Acta Neurol Scand 2011; 124(3):171-5) This suggests an interaction between vitamin D and biological mechanisms affecting susceptibility to depression. Currently, we have two main hypotheses: 1) Vitamin D regulates the hypothalamic stress axis in MS. Based on our findings that cortisol releasing hormone (CRH)-positive hypothalamic neurons in the brains of MS patients stained positive for the vitamin D receptor (VDR) and 1,25(OH)2D-24-hydroxylase (24-OHase). (smolders et al. J Neuropathol Exp Neurol 2013;72(2):91-105) 2) Vitamin D affects T cell cytokine profile and hereby the odds of developing depression. Also in non-MS depressed patients increased levels of pro-inflammatory cytokines are detected (Maes et al. Metab Brain Dis 2009; 24: 27-53). Vitamin D3 has shown to be a potent promotor of T cell regulation both in vitro and in vivo. (Smolders et al. J Neuroimmunol 2008;194:7-17 and Smolders et al. PLoS One 2010;5:e15235) The main goal of this study is to assess whether supplementation of high doses vitamin D3 results in a suppression of saliva cortisol day-curves in subjects with multiple sclerosis, and we will explore whether the pro-inflammatory cytokine profile of T lymphocytes is regulated.
Vitamin D3 solution
Placebo comparator
Patients receive 1dd 100ug vitamin D3 (drops) for 16 weeks
Inclusion Criteria: Female Relapsing Remitting MS At start of study > 6 weeks in clinical remission of disease Age > 18 years. Premenopausal Treated with either no immune-modulating treatment, or the currently registered MS modulating treatments: Interferon beta 1a (Rebif®), Interferon Beta 1b (Betaferon® or Avonex®), Glatiramer Acetate (Copaxone®), dimethylfumarate (Tecfidera®), teriflunomide (Aubagio®)) or fingolimod (Gilenya®). Exclusion Criteria: Any contraindication to vitamin D according to Summary of Product Characteristics: Hypercalcaemia, hypervitaminosis D, nephrolithiasis, diseases or conditions resulting in hypercalcaemia and/or hypercalciuria (incl. primary hyperparathyroidism), severe renal impairment . Use of dexamethasone or other systemic glucocorticosteroids <2 months prior to first study visit Supplementation of >=1000 IU/d (25µg) vitamin D2 or D3 Medical history of disturbed vitamin D/ calcium metabolism other than low intake Present clinical (major)depression Present treatment with anti-depressants, benzodiazepines, or neuroleptics. Treatment with high-dose dexamethasone for MS exacerbation during study. Pregnancy or the intention to become pregnant during the study period.
