Vitamin D3 Treatment in Pediatric Systemic Lupus Erythematosus
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Intervention: Vitamin D3 6000 IU; Vitamin D3 400 IU
Intervention description: Subjects will receive 6,000 IU of vitamin D3 by mouth daily until the subject's serum 25(OH) level is ≥ 40ng/mL at which point the supplementation dose will be reduced to 4,000 IU/day. Note: Subjects weighing <40 kilograms (kg) at study entry will receive their dose five days a week and all other subjects seven days a week.; Subjects will receive 400 IU/day of vitamin D3 daily by mouth.
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 5 Years
Maximum age: 20 Years
Healthy volunteers: No
Keywords: SLE; Vitamin D3; Vitamin D deficiency; IFN alpha expression

Summary:

      The primary objective of this study is to evaluate the effects of 18 weeks of high-dose
      vitamin D3 supplementation compared with standard-dose vitamin D3 supplementation on immune
      function, glucose homeostasis, and bone metabolism in children with systemic lupus
      erythematosus (SLE) and serum 25-hydroxyvitamin D [25(OH)D] levels ≤20 ng/mL.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent signed by the subject or parent/guardian as appropriate;
             child assent as appropriate;

          -  Before the age of 19, met at least 4 of the 11 modified American College of
             Rheumatology (ACR) 1982 Revised Criteria for the Classification of Systemic Lupus
             Erythematosus as updated in 1997;

          -  Date of SLE diagnosis (as described in Inclusion Criterion 2) at least 24 weeks prior
             to randomization;

          -  Serum 25-hydroxyvitamin D [25(OH)D] < 20 ng/mL at Screening;

          -  SELENA SLEDAI score > 0 and < 8 at Screening and at Baseline;

          -  If taking prednisone (or equivalent corticosteroid), the dose must be ≤ 15 mg/day or
             ≤0.5 mg/kg/day, whichever is lower, and stable for at least four weeks prior to
             randomization. Note, if subjects are taking steroids every other day, divide their
             dose by 2 to evaluate eligibility;

          -  Stable immunosuppressive dose for at least 12 weeks prior to randomization;

             --Immunosuppressive medications allowed include mycophenolate (MMF), azathioprine,
             methotrexate, antimalarial medications (e.g., hydroxychloroquine), cyclosporine A
             (CsA), tacrolimus, intravenous immune globulin (IVIG), and abatacept.

          -  Body weight > 25 kg;

          -  Able to swallow pills;

          -  Males and females with reproductive potential must agree to practice effective
             measures of birth control.

        Exclusion Criteria:

          -  Any condition or treatment that, in the opinion of the investigator, places the
             subject at an unacceptable risk as a participant in the trial;

          -  Current pharmacologic vitamin D2 or D3 intake > 800 IU daily or use of calcitriol at
             any dose over the past four weeks prior to randomization;

          -  Cyclophosphamide or IV glucocorticoid exposure within 12 weeks prior to randomization;

          -  Any BILAG A or B manifestation with the exception of a BILAG B mucocutaneous
             manifestation at screening, and excluding the renal BILAG criteria (see rituximab or
             belimumab criterion, below);

          -  Significant renal insufficiency defined as:

               -  Estimated GFR < 60 mL/min/1.73m^2 or estimated GFR < 90 mL/min/1.73m^2 with a
                  reduction of the GFR by > 15% from the last measurement;

               -  Urine dipstick value of 2+ or higher for protein, unless this is a stable value
                  from the last measurement or, urine protein-creatinine ratio ≥ 50 mg/mmol unless
                  the value represents an improvement of ≥ 25% from the last measurement.

          -  Rituximab or belimumab exposure use within 24 weeks prior to randomization;

          -  The following laboratory parameters at the Screening visit:

               -  Platelets < 50,000; WBC < 2,500; ANC < 1,000;

               -  Hemoglobin < 9 mg/dL;

               -  ALT, AST, bilirubin > 2x upper limit of normal (ULN);

               -  Hypercalcemia (calcium > ULN);

               -  Hypercalciuria (urinary calcium/creatinine ratio > 0.2).

          -  Primary hyperparathyroidism (known);

          -  History of nephrolithiasis (known);

          -  Diabetes mellitus requiring insulin therapy;

          -  Medications that interfere with vitamin D absorption;

          -  History of vertebral compression fractures (known);

          -  Pregnancy (girls ≥ 11 years of age must have a negative urine/serum pregnancy test);

          -  A history of non-adherence/non-compliance;

          -  Other investigational drug and/or treatment during the four weeks or seven half-lives
             of the other investigational drug prior to the start of study product dosing (Day 0),
             whichever is the greater length of time to enrollment;

          -  Current diagnosis of cancer or chronic infection such as Hepatitis B, Hepatitis C, or
             tuberculosis;

          -  Treatment with digoxin;

          -  Flu (influenza) vaccination within one week prior to randomization.