Overview

This trial is active, not recruiting.

Condition multiple sclerosis
Treatments cholecalciferol, placebo comparator
Phase phase 2
Sponsor Academic MS Center Limburg
Start date October 2014
End date October 2016
Trial size 54 participants
Trial identifier NCT02096133, 2014-000728-97, EMR200109_635

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Arm
(Experimental)
Patients receive 1dd 100ug vitamin D3 (drops) for 16 weeks
cholecalciferol Vigantol Oil
Vitamin D3 solution
(Placebo Comparator)
placebo drops during 16 weeks
placebo comparator
Placebo comparator

Primary Outcomes

Measure
The area under the curve (AUC) of the cortisol day curve
time frame: At baseline and after 16 weeks of supplementation.

Secondary Outcomes

Measure
The slope of the cortisol day-curve
time frame: At baseline and after 16 weeks of supplementation
The cortisol awakening response
time frame: At baseline and after 16 weeks of supplementation
Clinical outcomes on depression
time frame: At baseline and after 16 weeks of supplementation
Efficacy of supplementation
time frame: At baseline and after 16 weeks of supplementation. Side effects will also be checked at 8 weeks of supplementation.
Side effects
time frame: At baseline, after 8 and after 16 weeks

Eligibility Criteria

Female participants at least 18 years old.

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.

Additional Information

Official title Regulation of the Stress-axis by Vitamin D3 in Subjects With Multiple Sclerosis; a Double-blinded, Randomized, Placebo-controlled Study
Principal investigator Raymond Hupperts, MD, PhD
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.
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Academic MS Center Limburg.