Effect of Vitamin D3 on the IFN Alpha Signature in Patients With Systemic Lupus Erythematosus (ALE02)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 8
- 主要终点
- Percent of Participants With an IFN Alpha Signature Response at Week 12
研究概览
简要总结
The purpose of this study is to explore the impact of vitamin D3 on the expression of alpha interferon (IFN alpha) expression in systemic lupus erythematosus (SLE) patients with vitamin D deficiency.
详细描述
Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies with subsequent immune complex deposition and tissue inflammation. The role of interferon (IFN) alpha in the development of SLE has been repeatedly documented. Vitamin D deficiency is common among lupus patients. Vitamin D is recognized as a regulator of immune response. This study will explore the impact of vitamin D3 supplementation on IFN alpha expression in SLE patients.
The study will last approximately 12 weeks and consist of three treatment groups: 1.) Participants will receive vitamin D3 2000 IU daily 2.) Participants will receive vitamin D3 4000 IU daily 3.) Participants will receive a vitamin D3 placebo daily. There will be four study visits for each participant. Visits will occur at screening, study entry, and Weeks 6 and 12. Physical examination, vital signs, and blood and urine tests will occur at all visits. For females of childbearing potential, a pregnancy test will be performed at screening and Week 6.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of SLE by American College of Rheumatology (ACR) criteria
- •Serum 25-OH vitamin D level of 20 ng/mL or less
- •Stable disease at screening, defined as a modified Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA-SLEDAI) of 4 or less
- •Interferon (IFN) signature present. More information about this criterion can be found in the protocol
- •Positive anti-double-stranded (anti-ds) DNA antibody blood test at screening
- •If on corticosteroids, the dose must be less than 20 mg per day and stable for 4 weeks prior to screening and at study entry
- •If on immunosuppressive or immunomodulatory medication such as azathioprine, methotrexate, leflunomide, mycophenolate, or hydroxychloroquine, the dose must be stable for 3 months prior to screening and at study entry
- •If receiving a multivitamin or a vitamin D supplement, the dose of vitamin D must be 800 IU daily or less and stable for the 3 months prior to screening and at study entry
- •Agree to use effective contraceptive methods for the duration of the study
排除标准
- •Unwilling to stop using drugs or substances that may interfere with fat absorption
- •Hypercalcemia
- •Hypercalciuria
- •History of hyperparathyroidism
- •History of kidney stones
- •History of cancer, except cervical carcinoma in situ and resected basal and squamous cell carcinomas of the skin
- •Known history of chronic viral infections, including human immunodeficiency virus (HIV), Hepatitis B, and Hepatitis C
- •Known active tuberculosis
- •Any British Isles Lupus Assessment Group (BILAG) A or B manifestation with the exception of a BILAG B mucocutaneous manifestation
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) liver function tests greater than or equal to two times the upper limit of normal
- •Dialysis or serum creatinine greater than 1.5 mg/dL
- •Expectation by the investigator to increase corticosteroid or immunosuppressive or immunomodulatory medication dose at screening, study entry, or over the course of the study
- •Treatment with cyclophosphamide within 3 months of screening
- •Treatment with rituximab within 12 months of screening
- •Other investigational drug and or treatment during the 4 weeks or seven half lives of the other investigational drug prior to study entry
- •Drug or alcohol abuse within 6 months prior to study entry
- •Treatment with digoxin
- •Treatment with teriparatide
- •Any condition that, in the opinion of the investigator, would jeopardize the subject's safety following exposure to the study drug
- •Pregnant or breastfeeding
研究组 & 干预措施
vitamin D3 2000 IU
Participants in this arm take a vitamin D3 dose of 2000 international units (IU) daily by mouth for a duration of 12 weeks.
干预措施: Vitamin D3 (Drug)
vitamin D3 4000 IU
Participants in this arm take a vitamin D3 dose of 4000 international units (IU) daily by mouth for a duration of 12 weeks.
干预措施: Vitamin D3 (Drug)
vitamin D3 placebo
Participants in this arm take a vitamin D3 placebo daily by mouth for a duration of 12 weeks.
干预措施: Vitamin D3 placebo (Drug)
结局指标
主要结局
Percent of Participants With an IFN Alpha Signature Response at Week 12
时间窗: 0, Week 12
Presence of an Interferon (IFN) Alpha signature response is defined as: a reduction in expression from baseline (Screening) of at least 50% for 1 of 3 IFN Alpha responsive genes (Ifit1, Ifi44, Mx1) with concurrent expression in the remaining 2 genes at a level not more than 25% above baseline, or a reduction in expression from baseline of at least 25% for 2 of the 3 IFN Alpha responsive genes with concurrent expression in the third gene at a level of no more than 25% above baseline. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were considered as response failures during calculation.
次要结局
- Percent of Participants With IFN Alpha Signature at Week 12(0, Week 12)
- Percent of Participants With an IFN Alpha Signature Response at Week 6(0, Week 6)
- Change in Serum C3 Level From Baseline to Week 6(0, Week 6)
- Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12(0, Week 12)
- Percent of Participants With IFN Alpha Signature at Week 6(Week 6)
- qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 6(0, Week 6)
- qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 12(0, Week 12)
- qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 12(0, Week 12)
- Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6(0, Week 6)
- Ophthalmic BILAG Status at Week 12(Week 12)
- qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 6(0, Week 6)
- qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 12(0, Week 12)
- qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 6(0, Week 6)
- Change in SELENA-SLEDAI Total Score From Baseline to Week 12(0, Week 12)
- Constitutional BILAG Status at Week 12(Week 12)
- Gastrointestinal BILAG Status at Week 12(Week 12)
- Mucocutaneous BILAG Status at Week 12(Week 12)
- Renal BILAG Status at Week 12(Week 12)
- Change in Serum C3 Level From Baseline to Week 12(0, Week 12)
- Change in Serum C4 Level From Baseline to Week 12(0, Week 12)
- Change in Serum C4 Level From Baseline to Week 6(0, Week 6)
- Neuropsychiatric BILAG Status at Week 12(Week 12)
- Cardiorespiratory BILAG Status at Week 12(Week 12)
- Hematological BILAG Status at Week 12(Week 12)
- Musculoskeletal BILAG Status at Week 12(Week 12)
- Percent of Participants With Adverse Events of Grade 3 or Above(From start of study treatment through Week 12)