Vitamin D3 Effects on Immune Function in Pediatric Systemic Lupus Erythematosus (SLE)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 13
- 主要终点
- Percentage of Subjects by Treatment Arm Experiencing Any Adverse Event (AE) ≥ Grade 3
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Vitamin D3 6000 IU
6000 IU of vitamin D3 by mouth daily until the subject's serum 25(OH) level is ≥ 40ng/mL at which point the supplementation dose is 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.
干预措施: Vitamin D3 6000 IU (Drug)
Vitamin D3 400 IU
400 IU/day of vitamin D3 by mouth daily.
干预措施: Vitamin D3 400 IU (Drug)
结局指标
主要结局
Percentage of Subjects by Treatment Arm Experiencing Any Adverse Event (AE) ≥ Grade 3
时间窗: Baseline to 18 Weeks
Adverse event grading based on National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0
Change in Average IFN Module Expression Level
时间窗: Baseline to Week 18
No mechanistic analyses were performed due to recruitment feasibility issues.
次要结局
未报告次要终点