Vitamin D Supplementation in Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disorder. It mainly involves the skin, the joints, the nervous system and the kidney and may be life threatening. SLE is associated with production of autoantibodies and perturbations in regulatory T cells and T helper lymphocytes producing interleukin (IL)-17 (Th17 cells). Treatments include corticosteroids, hydroxychloroquine and immunosuppressive agents. Immunomodulatory effects of vitamin D supplementation in VITRO was recently described, notably the expansion of Treg able to suppress inflammatory responses mediated by CD4+ and CD8+ T cells and the decrease of Th17 cells.

Detailed Description
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Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disorder. It mainly involves the skin, the joints, the nervous system and the kidney and may be life threatening. SLE is associated with production of autoantibodies and perturbations in regulatory T cells and T helper lymphocytes producing interleukin (IL)-17 (Th17 cells). Treatments include corticosteroids, hydroxychloroquine and immunosuppressive agents. Immunomodulatory effects of vitamin D supplementation in VITRO was recently described, notably the expansion of Treg able to suppress inflammatory responses mediated by CD4+ and CD8+ T cells and the decrease of Th17 cells. Objective : To evaluate the cellular immune response after vitamin D supplementation in patients with SLE. Methods : This is an open prospective trial. SLE patients with hypovitaminosis D (< 30 ng/mL) receive vitamin D supplementation. 100 000 UI of cholecalciferol per week for 4 weeks then 100 000 UI of cholecalciferol per month for 6 months will be administered. All patients are followed after the beginning of vitamin D supplementation at month 2 and month 6. End points : Clinical and biological tolerance: Absence of hypercalcemia or lithiasis during and after vitamin D supplementation. Immunologic follow-up of T cells and B cells homeostasis (including Treg and Th17) and gene expression profile in PBMCs using TRANSCRIPTOMIC analysis, before, during and after vitamin D supplementation. Clinical efficacy: follow-up of clinical manifestations of SLE and disease activity score (SLEDAI) during and after vitamin D supplementation. Schedule : Duration of patients' inclusion period is estimated 3

Official Title
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Evaluation of Immunologic Response After Vitamin D Supplementation in Patients With Systemic Lupus Erythematosus

Conditions
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Vitamin D Deficiency

Intervention / Treatment
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* Drug: cholecalciferol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Systemic lupus erythematosus Age > 18 years Serum vitamin D levels [25(OH)D] < 30 ng/mL Low to moderate active disease without modification of associated treatments Exclusion Criteria: Pregnancy Serum 25(OH)D levels > 30 ng/mL Flare requiring modification of treatments

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cholecalciferol|100 000 UI of cholecalciferol per week during 4 then 100 000 UI of cholecalciferol per month for 6 months|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunologic follow-up of T cells and B cells homeostasis (including regulatory T cells and Th17 cells) and gene expression profile of PBMCs using TRANSCRIPTOMIC analysis, before, during and after vitamin D supplementation | Immunologic follow-up of T cells and B cells homeostasis (including regulatory T cells and Th17 cells) and gene expression profile of PBMCs using TRANSCRIPTOMIC analysis, before, during and after vitamin D supplementation | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical tolerance: Absence of Hypercalcemia and lithiasis during and after vitamin D supplementation | Clinical tolerance: Absence of Hypercalcemia and lithiasis during and after vitamin D supplementation | 6 months | 
| Clinical efficacy: follow-up of clinical manifestations of SLE and disease activity score (SLEDAI) | Clinical efficacy: follow-up of clinical manifestations of SLE and disease activity score (SLEDAI) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic lupus erythematosus, vitamin D supplementation, regulatory T cells, Th17 cells