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临床试验/NCT01195818
NCT01195818已完成不适用

Effect of RAS Inhibitors on Albuminuria, Hyperfiltration and Endothelial Dysfunction in a Sickle Cell Disease Population.

Assistance Publique - Hôpitaux de Paris1 个研究点 分布在 1 个国家目标入组 53 人开始时间: 2010年9月最近更新:
适应症
干预措施
相关药物

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

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

Experimental

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)

研究者

申办方类型
Other
责任方
Sponsor

研究点 (1)

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