Vitamin D3 and the Stress-axis in MS

NCT ID: NCT02096133

Last Updated: 2017-01-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-13
• Study Completion Date: 2016-11-07

Brief Summary

Patients 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.

Detailed Description

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.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Cholecalciferol

Patients receive 1dd 100ug vitamin D3 (drops) for 16 weeks

Group Type: EXPERIMENTAL

Cholecalciferol

Intervention Type: DRUG

Vitamin D3 solution

Placebo comparator

placebo drops during 16 weeks

Group Type: PLACEBO_COMPARATOR

Placebo comparator

Intervention Type: OTHER

Placebo comparator

Interventions

Cholecalciferol

Vitamin D3 solution

Intervention Type: DRUG

Placebo comparator

Placebo comparator

Intervention Type: OTHER

Other Intervention Names

Vigantol Oil

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Academic MS Center Limburg

OTHER

Sponsor Role: lead

Responsible Party

Raymond Hupperts

Prof. R.M.M. Hupperts, MD, PhD, neurologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Raymond Hupperts, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Academic MS Center Limburg, Orbis MC

Locations

Canisius Wilhelmina Ziekenhuis

Nijmegen, , Netherlands

Academic MS Center Limburg, Orbis Medical Center

Sittard-Geleen, , Netherlands

Countries

Netherlands

References

Rolf L, Damoiseaux J, Huitinga I, Kimenai D, van den Ouweland J, Hupperts R, Smolders J. Stress-Axis Regulation by Vitamin D3 in Multiple Sclerosis. Front Neurol. 2018 Apr 26;9:263. doi: 10.3389/fneur.2018.00263. eCollection 2018.

Reference Type: DERIVED

PMID: 29755397 (View on PubMed)

Other Identifiers

2014-000728-97

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EMR200109_635

Identifier Type: -

Identifier Source: org_study_id