Albuminuria Reduction With Renin Angiotensin System Inhibitors in SCA Patients (RAND)

June 17, 2015 updated by: Assistance Publique - Hôpitaux de Paris

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

53

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75020
        • Centre de la Drépanocytose, Service de Médecine Interne. Hôpital Tenon, 4 Rue de la Chine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RAS Inhibitors
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Comparison of albuminuria/ urinary creatinin ratio before and after a 6 months RAS inhibitor treatment period
Time Frame: 6 months RAS inhibitor treatment period
6 months RAS inhibitor treatment period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of albuminuria/ urinary creatinin ratio under RAS inhibitor treatment and after 1 month wash-out period
Time Frame: 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
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,)
6 months RAS inhibitor treatment period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2010

Primary Completion (Actual)

September 1, 2014

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

September 3, 2010

First Submitted That Met QC Criteria

September 3, 2010

First Posted (Estimate)

September 6, 2010

Study Record Updates

Last Update Posted (Estimate)

June 18, 2015

Last Update Submitted That Met QC Criteria

June 17, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P081110
  • AOR09063

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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