vitamin d3 treatment in pediatric systemic lupus erythematosus

Conditions: Systemic Lupus Erythematosus

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.

this is a multi-center, phase ii, 18-week, two arm, unblinded randomized clinical trial. seventy-eight pediatric subjects with sle and 25(oh)d levels ≤ 20 ng/ml will be randomized in a 1:1 ratio to receive either standard-dose (400 iu/day) or high-dose (6,000 iu/day) vitamin d3 for 18 weeks based upon weight at baseline. subjects randomized to the high-dose vitamin d3 treatment arm will receive 6,000 iu per day from baseline until the subject's vitamin d levels reach ≥ 40 ng/ml at which point the vitamin d3 dose will be reduced to 4,000 iu per day. subjects randomized to the high-dose treatment arm weighing \< 40 kg will receive supplementation five days per week and all other subjects will receive supplementation seven days a week. in addition to the baseline, and weeks 6, 12, and 18 visits, subjects randomized to the high-dose treatment arm will return at weeks 3 and 9 to assess for symptoms of vitamin d toxicity. if a subject in the high-dose arm is found to exhibit evidence of vitamin d toxicity at the week 12 visit, he/she will be asked to return to their clinical research site for an additional vitamin d toxicity assessment at week 15. study personnel will record each subject's interval history, assess adverse events, disease activity, and collect samples for safety and mechanistic assessments.

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 \ 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.

Keywords: sle vitamin d3 vitamin d deficiency ifn alpha expression