Genomic Effects of Glucocorticoids in Patients With Systemic Lupus Erythematosus
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Number of SLE Patients That Were Sampled for RNA-seq Differential Expression Analysis (Biological Replicates)
研究概览
简要总结
Background:
The immune system is the body's defense against bacteria and other harmful invaders. In people with systemic lupus erythematosus (SLE), the immune system becomes overactive and attacks healthy cells by mistake. Many people use glucocorticoids (GCs) to treat their SLE. GCs can calm down an overactive immune system by changing how the body reads genes. But GCs have side effects that can increase over time. Researchers want to learn more about how GCs work. This may help to develop new and better drugs for treating SLE without the side effects GCs have.
Objective:
To better understand how GCs affect the immune system in people with SLE.
Eligibility:
People age 18-80 with SLE.
Design:
Participants will be screened with a physical exam. They will have a health and medical history. They will have blood and urine tests. They will have an electrocardiogram to measure heart activity. For this, sticky pads are put on their chest, arms, and legs.
Participants will have a methylprednisolone infusion for about 30 minutes. It will be given through a needle in a vein.
Blood will be collected immediately before, 2 hours after, and 4 hours after the start of the infusion. Blood pressure and heart activity will be monitored. Participants will repeat some of the screening tests.
Participants will be contacted twice in the week after the infusion visit. They will discuss any health problems they are having.
详细描述
Study Design:
This is a study of the acute effects of glucocorticoids on the immune system of patients with SLE. Participants will undergo baseline blood collection prior to receiving a single intravenous (IV) dose of methylprednisolone sodium succinate. Participants will be randomized into 1 of 2 dose groups: 1 mg/kg or 250 mg. Blood will be collected again at 2 and 4 hours after the methylprednisolone infusion. Individual participation requires 2 visits to the NIH CC and 2 follow-up phone calls. Total length of individual subject participation including screening is 1-12 weeks. Blood samples will be processed for isolation of hematopoietic cell sub-populations (eg, neutrophils, B cells, plasmacytoid dendritic cells, CD4+ T cells, CD8+ T cells, monocytes, and natural killer cells). Laboratory studies will be performed on the purified cells, with the goal of understanding the human response to glucocorticoids in vivo at the level of circulating cell populations (eg, flow cytometry, mass cytometry), RNA (eg, RNA sequencing [RNA-seq], small-RNA-seq, real-time polymerase chain reaction [PCR]), DNA (eg, chromatin immunoprecipitation sequencing [ChIP-seq], methylation analysis, DNA sequencing, genotyping), and protein (eg, flow cytometry, mass spectrometry). At each time point, serum methylprednisolone levels will be measured.
Study Agent/ Intervention Description:
A single IV infusion of methylprednisolone sodium succinate at either 1 mg/kg or 250 mg.
Primary Objective:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Group A: Glucocorticoids 1 mg/kg dose
Participants with Systemic Lupus Erythematosus (SLE) received a single intravenous dose of methylprednisolone 1 mg/kg and blood was collected two hours and four hours after the start of the infusion.
干预措施: Solu-Medrol 1mg/kg (Drug)
Group B: Glucocorticoids 250 mg dose
Participants with Systemic Lupus Erythematosus (SLE) received a single intravenous dose of 250 mg of methylprednisolone and blood was collected two hours and four hours after the start of the infusion.
干预措施: Solu-Medrol 250 mg (Drug)
结局指标
主要结局
Number of SLE Patients That Were Sampled for RNA-seq Differential Expression Analysis (Biological Replicates)
时间窗: 2 hours and 4 hours post infusion
Number of of SLE patients that were sampled for RNA-seq differential gene expression analysis in glucocorticoid-treated immune cells. The analysis employed a cutoff value of \< 5% false-discovery rate (FDR) to select the transcripts that were considered differentially expressed at each time point. The resulting gene lists were contrasted to determine which genes were uniquely differentially expressed in different cell types.
次要结局
未报告次要终点