Vitamin D to Improve Endothelial Function in SLE
Condition: Atherosclerosis; Systemic Lupus Erythematosus
MeSH terms: Atherosclerosis; Lupus Erythematosus, Systemic
Intervention: Cholecalciferol
Intervention description: 5,000 International units versus 400 international units as an active comparator
Intervention MeSH terms: Vitamin D; Cholecalciferol; Vitamins
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: atherosclerosis; systemic lupus erythematosus; flow mediated dilation; interferon gene signature

Summary:

      Determine the effect of vitamin D repletion on flow mediated dilation (FMD, a measure of
      endothelial function) in vitamin D deficient systemic lupus erythematosus (SLE) patients. The
      investigators will enroll vitamin D deficient SLE patients and randomize them to receive
      either 400 IU or 5,000 IU of cholecalciferol (D3) daily and measure change in FMD as a
      measure of EC function at baseline and after 16 weeks of repletion.

      Determine mechanisms by which vitamin D repletion may improve endothelial function in vitamin
      D deficient SLE patients and in vitro.

      Determine effect of oral D3 repletion on the Type I interferon signature in WISH and ECs
      cultured with pre and post plasma from D3 treated lupus patients.

      Determine effect of D3 repletion on the number of circulating apoptotic and non-apoptotic EC
      and EPC ex vivo.

      Determine effect of exogenous 1,25(OH)D on IFN gene signature in WISH and ECs stimulated by
      pretreatment SLE plasma in vitro.

      Determine the effects of exogenous 1,25(OH)D on the phenotype of ECs cultured with
      pretreatment lupus plasma.

      This study is designed to efficiently test our hypothesis and begin to define
      interferon-dependent pathways through which vitamin D repletion can restore clinical and in
      vitro endothelial function.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of SLE per 1997 American College of Rheumatology Criteria(at least 4
             criteria present)

          -  Documented Vitamin D deficiency

          -  Able to give informed consent

        Exclusion Criteria:

          -  Using tobacco products

          -  Pregnant/Planning pregnancy

          -  Known Hypercalcemia (Serum Ca >10.4)

          -  Known Hypercalcuria (Calcium/Creatinine >0.8)

          -  Chronic active lupus nephritis or end stage renal disease or kidney stones

          -  Known Hyperparathyroidism

          -  Known chronic viral/mycobacterial infections

          -  Uncontrolled medical disease - Pl judgment

          -  Current drug or alcohol abuse

          -  Anticipated poor compliance/known neuropsychiatric disorders

          -  Hx of cardiovascular events (i.e. Ml, PVD, CVE)

          -  Subjects taking medications known to affect FMD in lupus subjects such as but not
             limited to fish oil, statins, will remain on stable doses throughout the study.