Vitamin D deficiency is associated with the risk of developing MS. Vitamin D treatment has therefore been tested as a background treatment for this pathology, with a seemingly modest clinical effect. Indeed, the first therapeutic trials using high doses of vitamin D (SOLAR and CHOLINE) did not show a significant effect on short-term relapses. However, these two studies showed a significant decrease in the radiological activity of MS on MRI, suggesting a significant immunomodulatory efficacy but a weak clinical benefit in the short term.

Vitamin D has a pleiotropic effect on the immune system inducing overall immunomodulation through transcriptomic modulations, under the control of many individual genetic factors. However, in vivo, only one therapeutic trial has compared the immunological effect of Vitamin D in healthy subjects and in patients with a first demyelinating episode. Analysis of PBMC by flow cytometric cell sorting based on a very small number of markers (CD3, CD8, IL-17, IFN-g) did not find any significant quantitative modulation of Th17 or of their production of IL-10, IL-17 and IFN-g after treatment with Vitamin D measured by ELISA. However, the evolution of anti-inflammatory lymphocyte populations has not been evaluated. A few in vitro studies suggest that the effect of vitamin D may be incomplete on the lymphocytes of MS patients.

The study investigators will use an immunological FACS approach to describe activation markers and measure the intensity of changes induced in healthy subjects after 3 months of high-dose cholecalciferol versus placebo treatment using the same protocol as the D-Lay MS (NCT01817166) study.

Inclusion Criteria:

• The patient must have given their free and informed consent and signed the consent form
• The patient must be a member or beneficiary of a health insurance plan
• Women of childbearing potential must have effective contraception during the study period. Effective contraception is defined by a low failure rate (less than 1% per year) when used correctly and consistently, such as implants, injectables, oral contraceptives, IUDs, abstinence, or partner vasectomy. A urine pregnancy test will be performed at inclusion.

Exclusion Criteria:

• The subject is participating in another therapeutic study, or is in a period of exclusion determined by a previous study
• The subject is unable to express their consent
• It is impossible to give the subject informed information
• The patient is under safeguard of justice or state guardianship
• Pregnant or breastfeeding
• Infectious disease or vaccination within previous 3 months
• Chronic psychiatric disease, or disease that, in the opinion of the investigator ,may put the patient at risk or affect compliance.
• Chronic inflammatory or dysimmune disease or subject on immunomodulatory or immunosuppressive therapy (including corticosteroids) within the last 3 months.
• Uncontrolled epilepsy.
• Known vitamin D deficiency secondary to active or other digestive disease (celiac disease, IBD, gastrectomy or bypass, cirrhosis, short bowel syndrome, nephrotic syndrome, hyperthyroidism, hypoparathyroidism, cancer, granulomatous pathology, lymphoma, rickettsiosis).
• History of hypercalcemia, osteopenia or osteoporosis, urinary lithiasis, heart rhythm disorders.
• Pathology requiring a daily intake of more than 1 gram of Calcium.
• Contraindication to vitamin D3 treatment as mentioned on the VIDAL documentation of UVEDOSE.
• Treatment affecting vitamin D metabolism other than corticosteroids: anti-epileptic drugs [phenobarbital, primidone, phenytoin], rifampicin, isoniazid, ketoconazole, 5-FU and leucovorin, thiazide diuretic.
• Active vitamin supplementation or dietary supplements rich in vitamin D.
• Present or past neurological symptoms that may suggest an undiagnosed inflammatory neurological pathology.