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

This study is currently recruiting participants.
Verified June 2012 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01195818
First received: September 3, 2010
Last updated: July 25, 2012
Last verified: June 2012
History of Changes
  Purpose

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).


Condition Intervention
Sickle Cell Disease
 Drug: RAS Inhibitors

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Effect of RAS Inhibitors on Albuminuria, Hyperfiltration and Endothelial Dysfunction in a Sickle Cell Disease Population.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Comparison of albuminuria/ urinary creatinin ratio before and after a 6 months RAS inhibitor treatment period [ Time Frame: 6 months RAS inhibitor treatment period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of albuminuria/ urinary creatinin ratio under RAS inhibitor treatment and after 1 month wash-out period [ Time Frame: 1 month wash-out period ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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,)


Estimated Enrollment: 60
Study Start Date: September 2010
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAS Inhibitors
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.
Other Name: RAS Inhibitors

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01195818

Contacts
Contact: François Lionnet, MD + 33 (01 56 01 62 17) francois.lionnet@tnn.aphp.fr

Locations
France
Centre de la Drépanocytose, Service de Médecine Interne. Hôpital Tenon, 4 Rue de la Chine Recruiting
Paris, France, 75020
Contact: FRANCOIS LIONNET, MD     + 33 (0)1 56 01 62 17     francois.lionnet@tnn.aphp.fr    
Principal Investigator: FRANCOIS LIONNET, MD            
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
  More Information

Publications:

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01195818     History of Changes
Other Study ID Numbers: P081110, AOR09063
Study First Received: September 3, 2010
Last Updated: July 25, 2012
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Albuminuria, hyperfiltration, RAS inhibitors, ADMA

Additional relevant MeSH terms:
Albuminuria
Anemia, Sickle Cell
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
 Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on June 17, 2013