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

This study has been terminated.
(Not enough inclusions)
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01096121
First received: March 29, 2010
Last updated: July 25, 2012
Last verified: June 2012
History of Changes
  Purpose

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 Intervention
Sickle Cell Disease
 Drug: Enalapril
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:

U.S. FDA Resources

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

Primary Outcome Measures:
  • Percentage of successful treatment of each arm [ Time Frame: at 9 months of treatment ] [ Designated as safety issue: No ]
    Successful treatment is defined by a reduction by half of the albuminuria/ creatinuria ratio (mg / mmol).


Secondary Outcome Measures:
  • Measure of albuminuria/ creatinuria ratio [ Time Frame: at 1, 3 and 6 month of treatment. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: June 2010
Study Completion Date: June 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 2 Drug: Placebo
Glucose
Other Name: Glucose
Experimental: 1
Enalapril
 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
Other Name: Enalapril

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.

  Eligibility

Ages Eligible for Study:   2 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01096121

Locations
France
Trousseau Hospital, Nephro-pediatric unit
Paris, France, 75012
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Tim ULINSKI, PH Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01096121     History of Changes
Other Study ID Numbers: P071222, AOM08052
Study First Received: March 29, 2010
Last Updated: July 25, 2012
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Angiotensin-converting enzyme inhibitors (ACE)
Renal disease
Microalbuminemia

Additional relevant MeSH terms:
Anemia, Sickle Cell
Kidney Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Urologic Diseases
Angiotensin-Converting Enzyme Inhibitors
 Enalapril
Enalaprilat
Enzyme Inhibitors
Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 22, 2013