E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing remitting multiple sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
Relapsing remitting multiple sclerosis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess whether supplementation of high doses vitamin D3 results in a suppression of saliva cortisol day-curves compared to treatment with placebo in female relapsing remitting MS patients. |
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E.2.2 | Secondary objectives of the trial |
•Does vitamin D3 supplementation result in a suppressed cortisone awakening response compared to treatment with placebo in female relapsing remitting MS patients?
•Does vitamin D3 supplementation result in a shift of CD4+ T cell cytokines to a less pro- and more anti-inflammatory profile compared to treatment with placebo in female relapsing remitting MS patients?
•Does vitamin D3 supplementation result in a reduced HADS depression/ FSSS fatigue score compared to treatment with placebo in female relapsing remitting MS patients?
•Does vitamin D3 supplementation result in an increased serum 25(OH)D/ calcium level and increased urinary calcium/ creatinine ratio compared to treatment with placebo in female relapsing remitting MS patients?
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 currently registered first-line MS modulating treatments (including Interferon beta 1a (Rebif®) or Interferon Beta 1b (Betaferon® or Avonex®), Glatiramer Acetate (Copaxone®), dimethylfumarate (Tecfidera®) or teriflunomide (Aubagio®)) or registered second-line MS modulating treatments (incl. fingolimod(Gilenya®) or natalizumab (Tysabri®)).
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E.4 | Principal exclusion criteria |
•Any contraindication to vitamin D according to Summary of Product Characteristics •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 •Treatment with high-dose dexamethason for MS exacerbation during study. •Pregnancy or the intention to become pregnant during the study period.
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E.5 End points |
E.5.1 | Primary end point(s) |
the area under the curve (AUC) of the cortisol day curve |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and after 16 weeks |
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E.5.2 | Secondary end point(s) |
The slope of the cortisol day-curve and the cortisol awakening response. Lymphocyte counts and assessment of cytokine profiles and surface markers. The depression sub-score of HADS and the FSSS fatigue score. The safety and biochemical efficacy of the intervention will be explored by measuring the serum concentrations of calcium, albumin, creatinine, and 25(OH)D levels, and by measuring the urinary calcium and creatinine levels . |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline and after 16 weeks. Safety parameters: in between, at 8 weeks. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Exploratory research at a point of action: interaction of vitamin D with stress-axis |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial will be defined as the date of the final clinical database lock after the last subject has completed the last visit at week 16. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |