Effect of RAS Inhibitors on Albuminuria, Hyperfiltration and Endothelial Dysfunction in a Sickle Cell Disease Population.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Comparison of albuminuria/ urinary creatinin ratio before and after a 6 months RAS inhibitor treatment period
研究概览
简要总结
The prevalence of Sickle Cell Associated Nephropathy (SCAN) is increasing and is a growing concern. Microalbuminuria is detected in the early onset of SCAN. Noteworthy, as in diabetic nephropathy, hyperfiltration seems to be a frequent finding, with, in our series, an overall incidence of 57 % and suggests a pathological links between glomerular hyperpressure and glomerulosclerosis which occurs several years after. Nitric oxide (NO) deficiency and the renin angiotensin system (RAS) are likely to be involved in the glomerular hyperpressure leading to hyperfiltration. Renin angiotensin antagonists are currently given for NEPHROPROTECTION in numerous nephropathy including SCAN despite few available reports. The percentage of decrease of albuminuria or the percentage of responders (ie patient normalizing albuminuria) has never been reported to our knowledge in SCAN patients at the time of hyperfiltration. The focus of our study is therefore to 1) Quantify albuminuria reduction after 6 months RAS treatment (primary end point); 2) Quantify glomerular filtration rate (GFR) reduction after 6 months of RAS treatment, and to test the hypothesis of a beneficial effect of RAS inhibitors on several biomarkers assessing hemolysis, NO inhibition and the endothelial damages (secondary end points). The ultimate aim of our study is to identify relevant (new) biomarkers associated to hyperfiltration and/or albuminuria decrease (/normalization).
详细描述
This is a non randomized prospective multicentered study testing the effect of RAS treatment with a wash out period at the end of the study.
Enrollment and informed consent will be performed in three AP-HP centers. Visit n° 1 will be performed in Hospital Tenon Center ( FONCTIONNEL Exploration Service) where final eligibility will be followed by several investigations aiming to measure albuminuria, basal GFR (51 cr EDTA clearance), cardiac parameters (doppler study); aortic stiffness (aortic pulse wave velocity) and endothelial dysfunction (microvascular laser-doppler, and blood and urine sample for assessment of several biomarkers).
At the end of the evaluation, Ramipril administration will be initiated (for at least six months).
Tolerance will be check up at visit n°2 (month 1) (clinical examination) and at the visit n°3 (month 6 ) (clinical examination). Patients will be contacted by the investigators every two month between each visit in order to evaluate tolerance. In case of cough with Ramipril, the treatment may be change by Irbesartan. Posology of treatment may be reduced in case of intolerance.
Treatment full dose (Ramipril 5mg/day or Irbesartan (300mg/day) will be obtained at the visit 2 and stopped at the end of visit 3:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 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
- •Homozygous sickle cell disease
- •> 18 years
- •Patient with social insurance
- •Albuminuria/ urinary creatinin > 10 mg/mmol creatinin (at 2 different times) and MDRD > 140 ml/min/1.73m
- •Written inform consent
排除标准
- •Hemoglobin SC or S-betathalassemia disease
- •Patient currently treated with: lithium, aspirin, antihypertensive drugs, non steroid-antiinflammatory drugs.
- •Pregnancy
- •Woman without contraception
- •Transfusion within the last 3 months
- •Intolerance to RAS inhibitors
- •Treatment with RAS in the last month
- •Patient with Congenital galactosemia or a malabsorption of glucose or lactase deficiency
- •Treatment with hydroxyurea began or changed in the last 3 months
- •Infection with HIV or C hepatitis
- •Angio-edema
研究组 & 干预措施
RAS Inhibitors
RAS Inhibitors
干预措施: RAS Inhibitors (Drug)
结局指标
主要结局
Comparison of albuminuria/ urinary creatinin ratio before and after a 6 months RAS inhibitor treatment period
时间窗: 6 months RAS inhibitor treatment period
次要结局
- Comparison of albuminuria/ urinary creatinin ratio under RAS inhibitor treatment and after 1 month wash-out period(1 month wash-out period)
- Comparison of glomerular Filtration Rate (51CR EDTA clearance) before and after a 6 months RAS inhibitor treatment period(6 months RAS inhibitor treatment period)
