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

Sickle Cell Disease Clinical Trial

— MADREPIEC  

Official title:

Interest of Angiotensin-converting Enzyme Inhibitors on Early Sickle Cell Renal Disease in Children. A Randomized, Double-blind Trial Enalapril vs Placebo.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01096121
• Other study ID #: P071222
• Secondary ID: AOM08052
• Status: Terminated
• Phase: N/A
• First received: March 29, 2010
• Last updated: July 25, 2012
• Start date: June 2010
• Est. completion date: June 2012

Study information

• Verified date: June 2012
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: June 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 18 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Kidney Diseases
• Sickle Cell Disease

Intervention

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
• Placebo
Glucose

Locations

Country	Name	City	State
France	Trousseau Hospital, Nephro-pediatric unit	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of successful treatment of each arm	Successful treatment is defined by a reduction by half of the albuminuria/ creatinuria ratio (mg / mmol).	at 9 months of treatment	No
Secondary	Measure of albuminuria/ creatinuria ratio		at 1, 3 and 6 month of treatment.	No
Secondary	Dosage of circulating forms of cell adhesion molecules ICAM-1 and VCAM-1		at the first day and at 9 months of treatment.	No