Hydroxychloroquine Sulfate Alleviates Persistent Proteinuria in IgA Nephropathy:a Single Center Prospective Randomized Controlled Study
试验速览
- 阶段
- 4 期
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- Incidence of Remission (Complete [CR] or Partial [PR]) at Week 24
研究概览
简要总结
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world.There is to date no curative therapy for patients with IgAN.It is considered that dendritic cells, Toll-like receptor (TLR) 9 and cytokines interleukin-6 (IL-6), and interferon-alpha (IFN-a) and tumor necrosis factor-alpha (TNF-α), play an important role in the aberrant mucosal response. Hydroxychloroquine is an antimalarial agent and had a notable impact on immune activation by the reduction of circulating activated immune cells that including decreased TLR-expressing cells, reduced IFN-secreting plasmacytoid dendritic cells, reduced production of inflammatory cytokines including interferon alpha, IL-6 and TNF alpha. Recent studies showed hydroxychloroquine had a benefit for renal remission and could retard the onset of renal damage in patients with lupus nephritis. hydroxychloroquine may have the potential effect in IgA nephropathy, alleviated the proteinuria and had the renal protect effect. This will be a single center, prospective, randomized, controlled study to assess the utility of hydroxychloroquine in IgAN patients.
详细描述
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world. Its estimated frequency is at least 2.5 cases per year per 100,000 adults. The glomerulopathy usually progressed slowly leading to end stage renal disease (ESRD). ESRD developed in 20%-40% of patients after 20 years. Given its complex and as yet incompletely understood pathogenetic mechanisms, there is to date no curative therapy for patients with IgAN.
Although pathogenesis of IgAN is still obscure, underglycosylated IgA-containing immune-complex including IgG or IgA antibodies against the hinge region of IgA1 are key factors for IgA nephropathy. Aberrant mucosal immune response might lead to increased production of underglycosylated IgA1. It is considered that dendritic cells, Toll-like receptor (TLR)9, and cytokines interleukin-6 (IL-6), , interferon-alpha (IFN-a) and tumor necrosis factor-alpha (TNF-α), play an important role in the aberrant mucosal response.
Hydroxychloroquine is an antimalarial agent and had a notable impact on immune activation by the reduction of circulating activated immune cells that including decreased TLR-expressing cells, reduced IFN-secreting plasmacytoid dendritic cells, reduced production of inflammatory cytokines including interferon alpha, IL-6 and TNF alpha. Recent studies showed hydroxychloroquine had a benefit for renal remission and could retard the onset of renal damage in patients with lupus nephritis.
Therefore, hydroxychloroquine, targeting dendritic cells, TLR, IL-6, IFN-α and TNF-α，may have the potential effect in IgA nephropathy, alleviated the proteinuria and had the renal protect effect. This will be a single center, prospective, randomized, controlled study to assess the utility of hydroxychloroquine added to valsartan in IgAN patients.
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
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •biopsy proven primary IgA nephropathy
- •age 18-60 years
- •proteinuria range from 0.5 to 1.5g/d
- •serum creatinine ≤132.6μmol/L
- •normal blood pressure or blood pressure ≤130/80 mmHg in patients with hypertension
排除标准
- •Hypersensitivity to chloroquine or to hydroxychloroquine
- •blood pressure <90/60 mm Hg
- •pregnancy and breastfeeding women
- •renal artery stenosis
- •Rapidly progressive renal insufficiency
- •systemic lupus erythematosus or other connective tissue diseases
- •Henoch- schoenlein purpura
- •other nephritis
- •diabetes mellitus
- •retinopathy
- •other contraindication of hydroxychloroquine
- •severe hepatic insufficiency
- •G6PD deficiency
- •psoriasis or porphyria
- •malignant hypertension
- •viral hepatitis or other infections
- •treatment with steroids or cytotoxic drugs during the previous three months
- •psychiatric disorder
- •not suitable for the study judged by investigator
研究组 & 干预措施
valsartan only:control group
valsartan (160mg/d)
干预措施: Valsartan (Drug)
hydroxychloroquine with valsartan:study group
valsartan (160mg/d) and Hydroxychloroquine Sulfate ( 400mg/d, twice daily)
干预措施: Hydroxychloroquine Sulfate (Drug)
hydroxychloroquine with valsartan:study group
valsartan (160mg/d) and Hydroxychloroquine Sulfate ( 400mg/d, twice daily)
干预措施: Valsartan (Drug)
结局指标
主要结局
Incidence of Remission (Complete [CR] or Partial [PR]) at Week 24
时间窗: 24 weeks
CR: proteinuria \<0.3 g/24 hr with no worsening of renal function (\<15% estimated glomerular filtration rate(eGFR) reduction from Baseline).PR: proteinuria \<3.5g/24 hrs but ≥0.3g/24 hrs and a decrease of \>50% from Baseline based on 24 hours pooled urine, with no worsening of renal function(\<15% eGFR reduction from Baseline). eGFR at Baseline will be defined as the Day 0 values.
次要结局
- Change from Baseline in Proteinuria Levels at the Indicated Time Points(Baseline and Weeks 4, 12, 24)
- Change from Baseline in Serum IgA Levels at the Indicated Time Points(Baseline and Weeks 4, 12, 24)
- Change from Baseline in Serum Creatinine Levels at the Indicated Time Points(Baseline and Weeks 4, 12, 24)
- Change from Baseline in eGFR at the Indicated Time Points(Baseline and Weeks 4, 12, 24)
- Change from Baseline in Serum Interleukin-6 Levels at the Indicated Time Points(Baseline and Weeks 4, 12, 24)
- Change from Baseline in Serum Tumor Necrosis Factor alpha Levels at the Indicated Time Points(Baseline and Weeks 4, 12, 24)
- Adverse Effects at the Indicated Time Points(Weeks 4, 12, 24)
- Change from Baseline in Serum Interferon alfa Levels at the Indicated Time Points(Baseline and Weeks 4, 12, 24)