The main aim of this study is to assess hypothesis A, and we will perform an exploratory analysis on hypothesis B.
ID
Source
Brief title
Condition
- Autoimmune disorders
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
We assess primarily the effect of vitamin D3 supplementation with a dose of
4000 IU/day (100µg/ day) for 16 weeks on the cortisol day curve.
Secondary outcome
Furthermore, we assess the effect of the intervention on the slope of the
cortisol day curve, a dexamethason suppression test, the cortisone awakening
response, the CD4+ T cell cytokine profile and the HADS depression/ FSSS
fatigue score, and we assess descriptively to which extent vitamin D levels in
the serum are elevated, and assess whether the participant experience
side-effects.
Background summary
MS patients are at risk for developing depressive symptoms. Also, impaired
vitamin D levels are associated with a higher risk of developing MS and with a
more severe MS course. Our group observed a relationship between vitamin D
status and the risk of developing depressive symptoms, suggesting an
interaction between vitamin D and biological mechanisms affecting
susceptibility to depression. Currently, we have two main hypotheses.
Hypothesis A: Vitamin D regulates the hypothalamic stress axis in MS. Both MS
patients and non-MS patients with a major depression have increased levels of
circulating cortisol, due to hyper-reactivity of hypothalamic-pituitary-adrenal
(HPA)-axis, also known as the stress axis. Previous research showed that
vitamin D receptors in the brain are particularly expressed in the hypothalamus
and that vitamin D also may affect cortisolcorticotrophin releasing hormone
(CRH)-positive cells. We postulate that vitamin D may regulate the release of
CRH, and hereby is able to suppress the activity of the HPA-axis and protects
MS patients for developing depressive symptoms in MS . Hypothesis B: Vitamin D
affects T cell cytokine profile and hereby the odds of developing depression.
In our previous studies, we showed that the cytokine profile of peripheral
blood CD4+ T cells correlates with vitamin D status in MS patients and that
vitamin D may promote T cell homeostasis in MS. Since both MS patients and
non-MS patients with a major depression display increased circulating levels of
pro-inflammatory cytokines and anti-depressants reduce those cytokines, an
inflammatory component may contribute to the development or presence of
depressive symptoms in MS , with whom vitamin D may interfere.
Study objective
The main aim of this study is to assess hypothesis A, and we will perform an
exploratory analysis on hypothesis B.
Study design
This will be a randomized, double-blinded, placebo-controlled clinical study.
Intervention
Patients have to take 100ug vitamine D3 solution a day for a period of 16
weeks.
Study burden and risks
Patients have to take the vitamin D solution every day and have to visit the
hospital 3 times for giving urine and blood samples. Also they have to collect
several salivasamples at the start and the end of the study, covering 4 full
days.
An elevation of serum calcium levels (hypercalcemia) has occasionally been
described in patients supplemented with high doses of vitamin D. A severe
hypercalcemia can give rise to complications as heart- and kidney faillure.
However, the amount of vitamin D that we supplement, de frequency of monitoring
and the exclusion of potential highrisk groups reduce this risk significantly.
P. Debeyelaan 25
Maastricht 6229 HX
NL
P. Debeyelaan 25
Maastricht 6229 HX
NL
Listed location countries
Age
Inclusion criteria
- relapsing remitting multiple sclerosis (revised McDonald criteria 2005)
- female
- age >18 years
- premenopausal
- At start of study > 6 weeks in clinical remission of disease
- use of no immune-modulating treatments or the currently registered firstline immune modulating therapies (including Interferon-beta (1a or 1b), glatiramer acetate, dimethylfumarate, teriflunomide) or second-line immune modulating therapies (incl. fingolimod (Gilenya) and natalizumab (Tysabri)).
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-000728-97-NL |
| ClinicalTrials.gov | NCT02096133 |
| CCMO | NL45995.096.14 |