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NCT Number: NCT01195818

Albuminuria Reduction With Renin Angiotensin System Inhibitors in SCA Patients

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).

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Key information

Conditions

Sickle Cell Disease Albuminuria Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Male Urogenital Diseases Pathological Conditions, Signs and Symptoms Proteinuria Signs and Symptoms Urination Disorders Urogenital Diseases Urologic Diseases Urological Manifestations

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

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

Paris, 75020, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

RAS Inhibitors

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.

Primary outcomes

  1. Comparison of albuminuria/ urinary creatinin ratio before and after a 6 months RAS inhibitor treatment period

    Time frame: 6 months RAS inhibitor treatment period

Secondary outcomes

  1. Comparison of albuminuria/ urinary creatinin ratio under RAS inhibitor treatment and after 1 month wash-out period

    Time frame: 1 month wash-out period

  2. Comparison of glomerular Filtration Rate (51CR EDTA clearance) before and after a 6 months RAS inhibitor treatment period

    Time frame: 6 months RAS inhibitor treatment period

    Study of at base line and under RAS treatment : 1) biomarkers evaluating NO metabolism (ADMA, arginase....), endothelial dysfunction (VEGF, PLGF and endothelin 1), hemolysis (LDH, haemoglobin, heme...) 2) heart and vessels ( cardiac doppler, aortic pulse wave velocity and microvascular brachial laser-Doppler,)

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study title

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

Acronym: RAND

Important dates

Study start
2010
Primary completion
2014
Study completion
2014
First posted
Sep 6, 2010
Registry last updated
Jun 18, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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