Peripheral Immunological Effects of High-dose Vitamin D Treatment in Healthy Subjects

NCT05654818 | Completed

• 2 other identifiers: CIVI/2021/ET-012022-002157-25
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Vitamin d Deficiency

Keywords

Multiple sclerosis; Immunomodulation; lymphocyte subset

Outcome Measures

Primary Outcomes (24)

• Change in Lymphocyte T CD4+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD3+/CD4+

  Month 3

• Change in T helper1 (Th1) Lymphocyte T CD4+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CXCR3+ /CCR6-

  Month 3

• Change in Th1*Lymphocyte T CD4+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CXCR3+/CCR+

  Month 3

• Change in naive Lymphocyte T CD4+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA+/CCR7+

  Month 3

• Change in effector memory Lymphocyte T CD4+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA-/CCR7-

  Month 3

• Change in central memory Lymphocyte T CD4+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA-/CCR7+

  Month 3

• Change in Teffector memory RA+ Lymphocyte T CD4+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA+/CCR7-

  Month 3

• Change in FOXP3 Treg / Treg Lymphocyte T CD4+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD25+/CD127+/FOXP3+

  Month 3

• Change in naive Treg Lymphocyte T CD4+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA+/FOXP3+

  Month 3

• Change in memory Treg Lymphocyte T CD4+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA-/FOXP3+

  Month 3

• Change in Tr1 Lymphocyte T cells CD4+ since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD49b+/LAG3+

  Month 3

• Change in Lymphocyte T CD8+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD3+/CD4-

  Month 3

• Change in naive Lymphocyte T CD8+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA+/CCR7+

  Month 3

• Change in effector memory Lymphocyte T CD8+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA-/CCR7-

  Month 3

• Change in central memory Lymphocyte T CD8+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA-/CCR7+

  Month 3

• Change in Teffector memory RA+ Lymphocyte T CD8+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA+/CCR7-

  Month 3

• Change in Tc1 Lymphocyte T CD8+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CXCR3+/CCR6-

  Month 3

• Change in Tc1* Lymphocyte T CD8+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CXCR3+/CCR6+

  Month 3

• Change in Tc2 Lymphocyte T CD8+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CXCR3-/CCR6-

  Month 3

• Change in Tc17 Lymphocyte T CD8+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CXCR3-/CCR6+

  Month 3

• Change in CD8 Tcreg / TcReg Lymphocyte T CD8+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD25+/CD127+/FOXP3+

  Month 3

• Change in naive Tcreg Lymphocyte T CD8+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA+/FOXP3+

  Month 3

• Change in memory Tcreg Lymphocyte T CD8+ cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA-/FOXP3+

  Month 3

• Change in Lymphocyte B cells since baseline

  Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD19+

  Month 3

Secondary Outcomes (21)

• lymphocyte subpopulations change in CD6 phenotype after 3 months of high dose vitamin D treatment or placebo

  Month 3

• lymphocyte subpopulations change in CD162 phenotype after 3 months of high dose vitamin D treatment or placebo

  Month 3

• lymphocyte subpopulations change in CD226 phenotype after 3 months of high dose vitamin D treatment or placebo

  Month 3

• lymphocyte subpopulations change in CD46 phenotype after 3 months of high dose vitamin D treatment or placebo

  Month 3

• lymphocyte subpopulations change in CD11a phenotype after 3 months of high dose vitamin D treatment or placebo

  Month 3

Study Arms (2)

Vitamin D

EXPERIMENTAL

Drug: Vitamin D

Control

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Vitamin D DRUG

100,000 UI

Vitamin D

Placebo DRUG

The placebo is identical in appearance to the active treatment: a drinkable solution in ampoules that is clear, yellowish in color with a slightly lemony odor and an oily, slightly sweet, lemony taste.

Control

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (1)

CHU de Nîmes

Nîmes, France

Location

MeSH Terms

Conditions

Vitamin D Deficiency; Multiple Sclerosis

Interventions

Vitamin D

Condition Hierarchy (Ancestors)

Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Eric Thouvenot

  CHU de Nimes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2022
• First Posted: December 16, 2022
• Study Start: April 13, 2023
• Primary Completion: October 10, 2023
• Study Completion: October 10, 2023
• Last Updated: December 10, 2025

Record last verified: 2025-12

Locations

FR (1)