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

Vitamin d Deficiency Clinical Trial

— VDSS  

Official title:

Peripheral Immunological Effects of High-dose Vitamin D Treatment in Healthy Subjects: Randomized, Single-center, Double-blind Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05654818
• Other study ID #: CIVI/2021/ET-01
• Status: Completed
• Phase: N/A
• Start date: April 13, 2023
• Est. completion date: October 10, 2023

Study information

• Verified date: May 2024
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: October 10, 2023
• Est. primary completion date: October 10, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Vitamin d Deficiency

Intervention

Drug:
• Vitamin D
100,000 UI
• Placebo
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.

Locations

Country	Name	City	State
France	CHU de Nîmes	Nîmes

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Lymphocyte T CD4+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD3+/CD4+	Month 3
Primary	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
Primary	Change in Th1*Lymphocyte T CD4+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CXCR3+/CCR+	Month 3
Primary	Change in naive Lymphocyte T CD4+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA+/CCR7+	Month 3
Primary	Change in effector memory Lymphocyte T CD4+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA-/CCR7-	Month 3
Primary	Change in central memory Lymphocyte T CD4+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA-/CCR7+	Month 3
Primary	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
Primary	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
Primary	Change in naive Treg Lymphocyte T CD4+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA+/FOXP3+	Month 3
Primary	Change in memory Treg Lymphocyte T CD4+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA-/FOXP3+	Month 3
Primary	Change in Tr1 Lymphocyte T cells CD4+ since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD49b+/LAG3+	Month 3
Primary	Change in Lymphocyte T CD8+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD3+/CD4-	Month 3
Primary	Change in naive Lymphocyte T CD8+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA+/CCR7+	Month 3
Primary	Change in effector memory Lymphocyte T CD8+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA-/CCR7-	Month 3
Primary	Change in central memory Lymphocyte T CD8+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA-/CCR7+	Month 3
Primary	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
Primary	Change in Tc1 Lymphocyte T CD8+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CXCR3+/CCR6-	Month 3
Primary	Change in Tc1* Lymphocyte T CD8+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CXCR3+/CCR6+	Month 3
Primary	Change in Tc2 Lymphocyte T CD8+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CXCR3-/CCR6-	Month 3
Primary	Change in Tc17 Lymphocyte T CD8+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CXCR3-/CCR6+	Month 3
Primary	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
Primary	Change in naive Tcreg Lymphocyte T CD8+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA+/FOXP3+	Month 3
Primary	Change in memory Tcreg Lymphocyte T CD8+ cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD45RA-/FOXP3+	Month 3
Primary	Change in Lymphocyte B cells since baseline	Percentage variation measured by Fluorescence Activated Cell Sorting of cells CD19+	Month 3
Secondary	lymphocyte subpopulations change in CD6 phenotype after 3 months of high dose vitamin D treatment or placebo	Measured by Fluorescence Activated Cell Sorting of cells	Month 3
Secondary	lymphocyte subpopulations change in CD162 phenotype after 3 months of high dose vitamin D treatment or placebo	Measured by Fluorescence Activated Cell Sorting of cells	Month 3
Secondary	lymphocyte subpopulations change in CD226 phenotype after 3 months of high dose vitamin D treatment or placebo	Measured by Fluorescence Activated Cell Sorting of cells	Month 3
Secondary	lymphocyte subpopulations change in CD46 phenotype after 3 months of high dose vitamin D treatment or placebo	Measured by Fluorescence Activated Cell Sorting of cells	Month 3
Secondary	lymphocyte subpopulations change in CD11a phenotype after 3 months of high dose vitamin D treatment or placebo	Measured by Fluorescence Activated Cell Sorting of cells	Month 3
Secondary	lymphocyte subpopulations change in CD49d phenotype after 3 months of high dose vitamin D treatment or placebo	Measured by Fluorescence Activated Cell Sorting of cells	Month 3
Secondary	lymphocyte subpopulations change in CLA phenotype after 3 months of high dose vitamin D treatment or placebo	Measured by Fluorescence Activated Cell Sorting of cells	Month 3
Secondary	Change in production of cytokine IL-10 in lymphocyte subpopulations after 3 months of high dose vitamin D treatment or placebo	Measured by Fluorescence Activated Cell Sorting of cells	Month 3
Secondary	Change in production of cytokine IFNg in lymphocyte subpopulations after 3 months of high dose vitamin D treatment or placebo	Measured by Fluorescence Activated Cell Sorting of cells	Month 3
Secondary	Change in production of cytokine IL-17 in lymphocyte subpopulations after 3 months of high dose vitamin D treatment or placebo	Measured by Fluorescence Activated Cell Sorting of cells	Month 3
Secondary	Change in plasma Vitamin D levels 3 months after baseline of high dose Vitamin D treatment versus placebo	Determination of 25-OH-D2 and 25-OH-D3 forms in nmol/L in plasma with the "vitamin D total II" kit	Month 3
Secondary	Change in 16sRNA levels 3 months after baseline of high dose Vitamin D treatment versus placebo		Month 3
Secondary	Nature of gut microbiota taxonomy 3 months after high dose Vitamin D treatment versus placebo	Number of operational taxonomic units	Month 3
Secondary	Nature of blood microbiota taxonomy 3 months after high dose Vitamin D treatment versus placebo	Number of operational taxonomic units	Month 3
Secondary	Percentage of gut microbiota taxonomy 3 months after high dose Vitamin D treatment versus placebo	Percentage of operational taxonomic units	Month 3
Secondary	Percentage of blood microbiota taxonomy 3 months after high dose Vitamin D treatment versus placebo	Percentage of operational taxonomic units	Month 3
Secondary	Diversity of gut microbiota 3 months after high dose Vitamin D treatment versus placebo	Shannon index	Month 3
Secondary	Diversity of blood microbiota 3 months after high dose Vitamin D treatment versus placebo	Shannon index	Month 3
Secondary	Beta diversity of gut microbiota 3 months after high dose Vitamin D treatment versus placebo	Bray-Curtis index	Month 3
Secondary	Beta diversity of blood microbiota 3 months after high dose Vitamin D treatment versus placebo	Bray-Curtis index	Month 3
Secondary	Describing the genetic determinants of vitamin D response using a Single Nucleotide Polymorphism (SNP) database	Description of individual SNPs	Month 3