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Angiotensin-converting Enzyme Inhibitors and Early Sickle Cell Renal Disease in Children (MADREPIEC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01096121
Recruitment Status : Terminated (Not enough inclusions)
First Posted : March 30, 2010
Last Update Posted : July 26, 2012
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

Patients with sickle cell anaemia may develop renal disease. In fact, renal disease occurred in 40% of adults patients (macroalbuminuria) with evolution to end-stage renal disease for half of them. Microalbuminuria is an early and sensitive marker of glomerular damage. It appears during the first decade and occurred in 20 to 25% of infants (2 to 18 years). Physiopathology of renal scarring is not well understood actually. Renal scarring might be due to glomerular hyperfiltration and vascular and endothelial damage. Angiotensin-converting enzyme inhibitors (ACE) were studied and used in diabetic nephropathy. In a study on 26 sickle cell adults, albuminuria was reduced about 50% by ACE compared to placebo after six months treatment. It might be interesting studying ACE efficacy in sickle cell children with microalbuminuria because renal disease is directly related to sickle cell and is not influenced by other cardiovascular risk factors like in adult patients.

We hypothesized to have a successful ACE treatment in more than 40% of cases after a nine months treatment period. A success is defined as a 50% reduction of the albuminuria/creatinuria ratio.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Enalapril Drug: Placebo Not Applicable

Detailed Description:

This is a multicenter study. In order to include 72 patients we should pre-include 400 patients.

They will be included in the study after signing the protocol consent. For final inclusion in the study, two albuminuria/creatinuria ratio should be over or equal to 3mg/mmol. If so, inclusion will be done and patient will be randomized (placebo/enalapril) by CLEANWEB software. A blood sample will be done.

Treatment tolerance will be check up at day 7 (blood sample for renal tolerance and clinical examination), month 1(clinical examination), month 3(clinical examination), month 6(clinical examination), and month 9 (clinical examination). Treatment efficacy will be evaluated by albuminuria/creatinuria ratio at month 1, month 3, month 6, and month 9. Physiopathology of ACE efficacy will be studied at first day and month 9 by dosage of ICAM-1 and VCAM-1.

Treatment plain posology (0.5mg/kg/day) will be progressively obtained on a three months period, beginning at 0.2mg/kg/day.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Interest of Angiotensin-converting Enzyme Inhibitors on Early Sickle Cell Renal Disease in Children. A Randomized, Double-blind Trial Enalapril vs Placebo.
Study Start Date : June 2010
Actual Primary Completion Date : January 2012
Actual Study Completion Date : June 2012

Arm Intervention/treatment
Placebo Comparator: 2 Drug: Placebo
Other Name: Glucose

Experimental: 1
Drug: Enalapril
  • during 1 month : 0,2 mg/kg/day
  • then during 2 months (if no adverse event): 0,35 mg/kg/day
  • and then during 6 months (if no adverse event): 0,5 mg/kg/day

Primary Outcome Measures :
  1. Percentage of successful treatment of each arm [ Time Frame: at 9 months of treatment ]
    Successful treatment is defined by a reduction by half of the albuminuria/ creatinuria ratio (mg / mmol).

Secondary Outcome Measures :
  1. Measure of albuminuria/ creatinuria ratio [ Time Frame: at 1, 3 and 6 month of treatment. ]
  2. Dosage of circulating forms of cell adhesion molecules ICAM-1 and VCAM-1 [ Time Frame: at the first day and at 9 months of treatment. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Sickle cell disease (SS, SC, Sb thalassemia, SD Punjab)
  • Affiliation to French Health benefits
  • Signed informed consent
  • Albuminemia / Creatinemia >= 3 mg / mmol (on 2 samples)

Exclusion Criteria:

  • Albuminemia / Creatinemia > 100 mg / mmol
  • Hypersensibility to enalapril
  • Angio-oedemas due to a previous treatment by ACE
  • idiopathic or hereditary angio-oedemas
  • cerebral echo-doppler
  • treatment by lithium digoxine
  • treatment by other ACE
  • congenital galactosemia
  • Pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01096121

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Trousseau Hospital, Nephro-pediatric unit
Paris, France, 75012
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
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Principal Investigator: Tim ULINSKI, PH Assistance Publique - Hôpitaux de Paris
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Responsible Party: Assistance Publique - Hôpitaux de Paris Identifier: NCT01096121    
Other Study ID Numbers: P071222
AOM08052 ( Other Identifier: Assistance Publique - Hôpitaux de Paris )
First Posted: March 30, 2010    Key Record Dates
Last Update Posted: July 26, 2012
Last Verified: June 2012
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Angiotensin-converting enzyme inhibitors (ACE)
Renal disease
Additional relevant MeSH terms:
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Kidney Diseases
Anemia, Sickle Cell
Urologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents