Albuminuria Reduction With Renin Angiotensin System Inhibitors in SCA Patients

NCT ID: NCT01195818

Last Updated: 2015-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2014-09-30

Brief Summary

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).

Detailed Description

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:

Assessment of RAS treatment effect on albuminuria, GFR, heart, aorta and microvessels will be performed at visit 3 (under RAS treatment) with the same procedure as visit 1.

Visit 4 will be performed after a 1 month wash out period in order to check whether the expected reduction of albuminuria under RAS treatment is sustained or not.

Conditions

Sickle Cell Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

RAS Inhibitors

RAS Inhibitors

Group Type: EXPERIMENTAL

RAS Inhibitors

Intervention Type: DRUG

Clinical trial testing the effect of RAS inhibitors (Ramipril or Irbesartan)on sickle cell disease patients wit hyperfiltration and albuminuria for a six month period followed by one month wash out period. Drug will be given after the first GFR measurement on a daily basis with a full dose given after the first month.

Interventions

RAS Inhibitors

Clinical trial testing the effect of RAS inhibitors (Ramipril or Irbesartan)on sickle cell disease patients wit hyperfiltration and albuminuria for a six month period followed by one month wash out period. Drug will be given after the first GFR measurement on a daily basis with a full dose given after the first month.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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/1.73m2.
• Written inform consent

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Centre de la Drépanocytose, Service de Médecine Interne. Hôpital Tenon, 4 Rue de la Chine

Paris, Paris, France

Countries

France

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Other Identifiers

AOR09063

Identifier Type: -

Identifier Source: secondary_id

P081110

Identifier Type: -

Identifier Source: org_study_id