A Pilot, Prospective, Randomized, Open-label, Blinded Endpoint (Probe) Histopathology Trial to Assess the Effects of ACE- Inhibition Therapy on Glomerular Proliferative Lesions in Patients With Extracapillary Glomerulonephritis
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- The extent of extracapillary proliferation on light microscopy, measured as % of total glomeruli with proliferative lesions at post-treatment repeat biopsy.
研究概览
简要总结
The natural course of extracapillary glomerulonephritis is severe leading to End-Stage Renal Disease (ESRD) or death in most cases. Despite immunosuppressive treatment, long-term renal outcome remains poor since active crescents usually progress to fibrotic scars with glomerular occlusion and disruption.In experimental models Angiotensin Converting Enzyme (ACE)-inhibitor therapy targeting the over-expression of angiotensin type 1 (AT1) receptors, that are responsible for dysregulated proliferation of parietal cell progenitors, blocks the formation of crescents and their fibrotic evolution. Should these drugs have similar effects in humans, ACE-inhibitor therapy on top of standard immunosuppression might be instrumental to prevent ESRD and promote renal function recovery in clinical practice.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Rapidly progressive renal failure associated with acute nephritic syndrome and/or nephrotic syndrome;
- •Histology evidence of extracapillary proliferation with less than 50% of sclerotic glomeruli and associated with:
- •Type I: Anti-Glomerular Basement Membrane (GBM) antibody glomerulonephritis,
- •Type II: Pauci-immune vasculitis or Anti Neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis;
- •Type III: Immune-complex mediated glomerular diseases: Proliferative lupus nephritis (LN), IgA nephropathy (IgAN)/ Schönlein-Henoch purpura, Type I membranoproliferative glomerulonephropathy (MPGN), Primary or secondary membranous nephropathy (MN), Primary or idiopathic immune complex glomerulonephritis.
- •Clinical indication to immunosuppressive therapy;
- •No specific indication to treatment with Renin Angiotensin System (RAS) inhibitors such as heart failure or coronary ischemic disease;
- •Written informed consent.
排除标准
- •Pre-existing advanced chronic renal failure (creatinine clearance less than 20 ml/min/1.73m2);
- •Evidence of B or C virus active infection;
- •HIV infection;
- •Recent diagnosis of malignancy;
- •Prolonged bleeding time and any other contraindication to kidney biopsy evaluation;
- •Any specific contraindication to ACE inhibitor therapy (that is: history of angioedema or other treatment-related serious adverse events);
- •Pregnancy or lactating;
- •Women of childbearing potential without following a scientifically accepted form of contraception;
- •Inability to understand the risks and benefit of the study or evidence of an uncooperative attitude;
- •Legal incapacity.
研究组 & 干预措施
Lisinopril
Patients will receive, in addition to standard immunosuppressive therapy, lisinopril starting with 5 mg/day, then progressively up-titrated to reach the maximum tolerable dose (target dose) for 18 months.
干预措施: Lisinopril (Drug)
结局指标
主要结局
The extent of extracapillary proliferation on light microscopy, measured as % of total glomeruli with proliferative lesions at post-treatment repeat biopsy.
时间窗: Changes from baseline and 6 and 18 month.
次要结局
- Expression of parietal cell proliferation markers at glomerular level, graded on a scale of 0 to 3 (0: no staining, 1: mild, 2: moderate, 3: strong diffuse(Changes from baseline and 6 and 18 month.)
- Glomerular Filtration Rate (GFR) measured by iohexol plasma clearance(Changes from baseline and 6, 12 and 18 month.)
- Number of fibrosclerotic crescents(Changes from baseline and 6 and 18 month.)
研究者
Monia Lorini
EC Secretary
A.O. Ospedale Papa Giovanni XXIII